Moderna COVID-19 vaccines
Moderna - National Institute of Allergy and Infectious Diseases (NIAID)
Spikevax (original); elasomeran; mRNA-1273; TAK-919; Spikevax bivalent (original + omicron BA.1); elasomeran + imelasomeran; mRNA-1273.214; Spikevax bivalent (original + omicron BA.4/BA.5); elasomeran + davesomeran; mRNA-1273.222
Authorization
Moderna COVID-19 vaccine (original strain)
World Health Organization Emergency Use Listing Procedure
Listed for emergency use on 30 April 2021 [WHO, 2021 ].
EUL/WHO Authorization: Authorized for emergency use in individuals 18 years of age and older [WHO, 2021 ].
SAGE/WHO Recommendation: Recommended for individuals 6 months of age and older [WHO, 2022 ].
European Commission (based upon the recommendation of the European Medicines Agency)
Authorized for emergency use (Conditional Marketing Authorization).
6 January 2021: For individuals 18 years of age and older [EMA , 2021 ].
23 July 2021: For individuals from 12 to 17 years of age [EMA, 2021 ].
24 February 2022: For individuals from 6 to 11 years of age [EMA, 2022 ]
Regulatory Authorities of Regional Reference in the Americas
National Administration of Drugs, Foods and Medical Devices (ANMAT, Argentina)
4 October 2021: Authorized for emergency use in individuals 12 years of age and older [MINISTERIO DE SALUD DE ARGENTINA, 2021 ].
Brazilian Health Regulatory Agency (ANVISA, Brazil)
Not authorized.
Health Canada [Government of Canada, 2022 ]
Authorized for emergency use on 23 December 2020.
17 March 2022: Authorized for emergency use in individuals 6 years of age and older.
14 July 2022: For individuals 6 months of age and older.
Public Health Institute (ISP, Chile) [Instituto de Salud Pública de Chile, 2022 ].
Authorized for emergency use on 03 February 2022.
06 April 2022: For individuals 6 years of age and older.
08 July 2022: For individuals 2 years of age and older.
23 August 2022: For individuals 6 months of age and older [Instituo de Salud Pública, 2022 ].
National Institute of Food and Drug Monitoring (INVIMA, Colombia)
Authorized for emergency use on 25 June 2021 [INVIMA, 2021 ].
20 September 2021: For individuals from 12 years of age and older [INVIMA, 2021 ].
Center for the State Control of Drug Quality (CECMED, Cuba)
Not authorized.
U.S. Food and Drug Administration [FDA, 2022 ].
Authorized for emergency use.
18 December 2020: Emergency Use Authorization (EUA) in individuals 18 years of age and older [FDA, 2022 ].
17 June 2022: Emergency Use Authorization (EUA) for individuals from 6 months to 17 years of age [FDA, 2022 ].
Federal Commission for the Protection against Sanitary Risk (COFEPRIS, Mexico)
Authorized for emergency use on 18 August 2021 [Gobierno de México, 2021 ].
Authorization in jurisdictions in Latin America and the Caribbean
Curaçao
Bolivia
Guadeloupe
Guatemala
Guyana
Haiti
Honduras
Paraguay
Peru
Puerto Rico
Saint Vincent and the Grenadines
San Martin
Sint Eustatius
Suriname
Trinidad and Tobago
Authorization in other jurisdictions
Listed by alphabetical order
Andorra
Australia
Austria
Bangladesh
Belgium
Bhutan
Botswana
Brunei
Bulgaria
Congo
Croatia
Cyprus
Czechia
Denmark
Egypt
Estonia
Faroe Islands
Fiji
Finland
France
Germany
Ghana
Greece
Greenland
Hungary
Iceland
India
Indonesia
Israel
Italy
Japan
Kenya
Kuwait
Latvia
Libya
Liechtenstein
Lithuania
Luxembourg
Malawi
Malaysia
Maldives
Malta
Micronesia
Moldova
Mongolia
Nepal
Netherlands
Nigeria
Norway
Oman
Pakistan
Philippines
Poland
Portugal
Qatar
Romania
Rwanda
Saba
Saudi Arabia
Seychelles
Singapore
Slovakia
Slovenia
South Korea
Spain
Sri Lanka
Sweden
Switzerland
Taiwan
Thailand
Ukraine
United Arab Emirates
United Kingdom
Vietnam
West Bank
Adapted Moderna COVID-19 vaccines
Spikevax bivalent (original + omicron BA.1)
World Health Organization Emergency Use Listing Procedure
Not authorized.
European Commission (based upon the recommendation of the European Medicines Agency)
Authorized for emergency use (Conditional Marketing Authorization) [EMA, 2022 ].
01 September 2022: For individuals 12 years of age and older.
19 November 2022: For individuals 6 years of age and older.
Regulatory Authorities of Regional Reference in the Americas
National Administration of Drugs, Foods and Medical Devices (ANMAT, Argentina)
Not authorized.
Brazilian Health Regulatory Agency (ANVISA, Brazil)
Not authorized.
Health Canada
01 September 2022: Authorized for emergency use for individuals 18 years of age and older [Health Canada, 2022 ].
Public Health Institute (ISP, Chile)
29 September 2022: Authorized for emergency use in individuals 18 years of age and older [ISP, 2022 ].
National Institute of Food and Drug Monitoring (INVIMA, Colombia)
Not authorized.
Center for the State Control of Drug Quality (CECMED, Cuba)
Not authorized.
U.S. Food and Drug Administration
Not authorized.
Federal Commission for the Protection against Sanitary Risk (COFEPRIS, Mexico)
Not authorized.
Authorization in jurisdictions in Latin America and the Caribbean
Chile
Authorization in other jurisdictions
Australia
Austria
Belgium
Bulgaria
Canada
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Japan
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Singapore
Slovakia
South Korea
Spain
Sweden
Switzerland
Taiwan
United Kingdom
Spikevax bivalent (original + omicron BA.4/BA.5)
World Health Organization Emergency Use Listing Procedure
Not authorized.
European Commission (based upon the recommendation of the European Medicines Agency)
Authorized for emergency use (Conditional Marketing Authorization).
19 October 2022: For individuals 12 years of age and older [EMA, 2022 ].
Regulatory Authorities of Regional Reference in the Americas
National Administration of Drugs, Foods and Medical Devices (ANMAT, Argentina)
Not authorized.
Brazilian Health Regulatory Agency (ANVISA, Brazil)
Not authorized.
Health Canada
03 November 2022: Authorized for emergency use in individuals 18 years of age and older [Health Canada, 2022 ].
Public Health Institute (ISP, Chile)
20 December 2022: Authorized for emergency use in individuals 12 years of age and older [Instituto de Salud Pública de Chile, 2022 ].
National Institute of Food and Drug Monitoring (INVIMA, Colombia)
Not authorized.
Center for the State Control of Drug Quality (CECMED, Cuba)
Not authorized.
U.S. Food and Drug Administration
Authorized for emergency use [FDA, 2022 ].
31 August 2022: Emergency Use Authorization (EUA) for individuals 18 years of age and older.
12 October 2022: Emergency Use Authorization (EUA) for individuals 6 years of age and older.
8 December 2022: Emergency Use Authorization (EUA) for individuals 6 months of age and older.
Federal Commission for the Protection against Sanitary Risk (COFEPRIS, Mexico)
Not authorized.
Authorization in jurisdictions in Latin America and the Caribbean
Not authorized.
Authorization in other jurisdictions
Austria
Belgium
Bulgaria
Canada
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Japan
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United States
Manufacturing
Manufacturer
Drug substance [World Health Organization, 2020 ]
Lonza Group. Visp, Switzerland.
[MODERNA TX INC. & LONZA SALES LTD, 2020 ].
Moderna TX Inc. Norwoord, MA, USA.
Lonza Biologics, Inc. Portsmouth, NH, USA.
Other manufacturers
Drug Product [World Health Organization, 2020 ]
Rovi Pharma Industrial Services, S.A. Spain. Principal manufacturers of Moderna COVID-19 vaccine.
Catalent Indiana, USA, provides vial filling and packaging [Rick Mullin, 2021 ].
Baxter Pharmaceutical Solutions (United States) produces the drug product of the vaccine.
Samsung Biologics 300, Republic of Korea.
Adapted Moderna COVID-19 vaccines
Spikevax bivalent (original + omicron BA.1)
Manufacturers
Moderna Biotech Spain, S.L. Madrid, Spain [EMA, 2022 ].
Spikevax bivalent (original + omicron BA.4/BA.5)
Manufacturers
Moderna Biotech Spain, S.L. Madrid, Spain [EMA, 2022 ].
Moderna TX Inc., USA [FDA, 2022 ].
General characteristics
The Moderna is an RNA vaccine composed of nucleoside-modified mRNA (modRNA). The synthetic mRNA is a single-stranded, 5'-capped messenger RNA encoding the SARS-CoV-2 spike (S) glycoprotein of SARS-CoV-2 virus stabilized in its prefusion conformation (S-2P antigen). S-2P consists of the SARS-CoV-2 glycoprotein (S glycoprotein) with a transmembrane anchor and an intact S1-S2 cleavage site. S-2P is stabilized in its prefusion conformation by two consecutive proline substitutions at amino acid positions 986 and 987, at the top of the central helix in the S2 subunit [Wrapp D, 2020 ]. The S glycoprotein mediates host cell attachment and is required for viral entry [Corbett KS, 2020 ].
It is important for the immune system to respond to the virus at the prefusion stage because it would probably be too late for the immune system to intervene at the postfusion stage when the virus is entering into the cell [Xia X, 2021 ]. Proline substitution is one of the main techniques reported to stabilize the SARS-CoV-2 spike at prefusion conformation. Spike protein variants can exhibit different levels of expression in comparison to the parental construct, and improved ability to withstand heat stress, storage temperature and resistance to freeze-thaw cycles [Hsieh CL, 2020 ]
The mRNA sequence encoding the protein was synthesized using an optimized T7 RNA polymerase-mediated transcription reaction with complete replacement of uridine by N1-methyl-pseudouridine [Corbett KS, 2020 ]. The reaction included a DNA template containing the immunogen open reading frame flanked by 5′untranslated region (UTR) and 3′UTR sequences and was terminated by an encoded polyA tail [Corbett KS, 2020 ].
Assembling mRNA using pseudouridine, a nucleoside variant naturally occurring in the body, reduces the response of dendritic cells, interferon-associated genes and other components of the immune system to trigger an inflammatory response. [Karikó K, 2008 ].
One way a vaccine mRNA molecule can be modified is by placing it between two RNA untranslated regions which stabilize the mRNA and optimize it for translation. The ends of the mRNA, known as 5‘ and 3‘ ends, can be modified by the addition of a cap and a poly(A) tail. The cap serves as a recognition signal for the cellular ribosome to bind and translate the mRNA and the poly(A) tail stabilizes the protein and further enhances translation of the protein [Schlake T, 2012 ].
The mRNA is encapsulated in lipid nanoparticles through a modified ethanol-drop nanoprecipitation process [Hassett KJ, 2019 ].
The modification of the lipid nanoparticles improves the immune response and improves tolerability [Hassett KJ, 2019 ].
After injection, body cells take up the lipid nanoparticle, delivering the mRNA sequence into cells for translation into viral protein and then initiating the immune response against COVID-19 [Hassett KJ, 2019 ]. The membrane-bound spike protein of SARS-CoV-2 is expressed and then recognized by immune cells as a foreign antigen. This elicits both T-cell and B-cell responses to generate neutralizing antibodies, which may contribute to protection against COVID-19.
Ingredients
The vaccine contains the following ingredients:
Active ingredient
One dose (0.5 mL) contains 100 micrograms of nucleoside-modified messenger RNA encoding the SARS-CoV-2 spike glycoprotein (S) stabilized in its prefusion configuration.
Excipients
Lipid SM-102
Cholesterol
1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)
1,2-Dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000 DMG)
Trometamol
Trometamol hydrochloride
Acetic acid
Sodium acetate trihydrate
Sucrose
Water for injections
Spikevax bivalent (original + omicron BA.1)
Active ingredient
One dose (0.5 mL) contains 25 micrograms of elasomeran and 25 micrograms of imelasomeran, a COVID-19 mRNA Vaccine (embedded in lipid nanoparticles).
Excipients
SM-102 (8-{(2-hidroxietilo)[6-oxo-6-(undeciloxi)hexil]amino}octanoato de heptadecan-9-ilo)
Cholesterol
1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC),
1,2-Dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000-DMG)
Trometamol,
Trometamol hydrochloride
Acetic acid
Sodium acetate trihydrate
Sucrose
Water for injections.
Spikevax bivalent (original + omicron BA.4-5)
Active ingredient
One dose (0.5 mL) contains 25 micrograms of elasomeran and 25 micrograms of davesomeran
Excipients
SM-102, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)
1,2-Dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000-DMG)
Trometamol
Trometamol hydrochloride
Acetic acid
Sodium acetate trihydrate
Sucrose
Water for injections.
Risk considerations
Risk of insertional mutagenesis
Unlike DNA vaccines, which might carry a small risk of insertional mutagenesis and integration, mRNA does not have the potential to integrate into the host genome and is degraded naturally during the process of antigen expression [Stenler S, 2014 ].
Risk of infection
Moderna COVID-19 vaccine is a non-replicating platform. This means the delivered mRNA does not carry an intrinsic risk for infection [GAVI,2020 ]. Additionally, contaminating microorganisms in mRNA vaccines are unlikely because the manufacturer does not need bacterial cell culture [Pardi N, 2018 ].
Inflammatory reactions
mRNA vaccines have a more pronounced proinflammatory nature. This feature might provide a self-adjuvant property but also can result in local and systemic reactions
[Liu MA, 2019 ]. However, a proposed mechanism for possible autoimmune responses is via the induction of type I interferon, which has been observed in preclinical studies [Pepini T, 2017 ].
Allergic reactions
Most immediate allergic reactions associated with vaccines are related with excipients
[Stone CA, 2019 ]. Polyethylene glycols (PEG) are frequently used as excipients in many liquid and solid formulations of medications and are also used to stabilize the lipid nanoparticle containing the mRNA of Moderna COVID-19 vaccine. Therefore, PEG constitutes the main candidate for explaining the cause of allergic reactions to this vaccine [Stone CA, 2019 ].
PEG itself has not previously used in other vaccines but polysorbate, a closely related compound, has been implicated in allergic reactions to other vaccines [Stone CA, 2019 ].
Dosing and schedule
Moderna COVID-19 vaccine (original strain)
The recommended schedule for the Moderna COVID-19 vaccine is: [WHO, 2022 ]
For children aged 6 months to 5 years: a series of two doses (25 μg, 0.25 ml each) 4 weeks apart.
For children aged 6 to 11 years: a series of two doses (50 μg each) 4 weeks apart.
For persons 12 years of age and older: a series of two doses (100 μg, 0.5 ml each) 4 weeks apart.
WHO recommends an interval between the first and second dose of 4 to 8 weeks, preferably extending it up to 8 weeks.
The preferred site of injection is the deltoid muscle of the upper arm.
This vaccine is presented as:*
Suspension for intramuscular injection provided in a multidose vial (each 0.5 mL dose containing 100 μg) indicated for persons aged 12 and older [WHO, 2021 ].
Suspension for intramuscular injection provided in a multidose vial with the label "BOOSTER DOSE ONLY" (each 0.5 mL dose containing 50 μg) [FDA, 2022 ]
Pediatric formulation: suspension for intramuscular injection provided in a multidose vial (doses of 25 μg in 0.25 mL per vial) indicated for persons aged 6 months to 5 years (dark blue cap vial with magenta border label) [FDA, 2022 ].
Pediatric formulation: suspension for intramuscular injection provided in a multidose vial (doses of 50 μg in 0.5 mL per vial) indicated for persons aged 6 to 11 years (dark blue cap vial with teal border label) [FDA, 2022 ].
*labeling depends on the availability of supply for each country [WHO, 2021 ], [FDA, 2022 ].
Booster dose [WHO, 2022 ]
A booster dose (50 µg for adults) is recommended for the highest priority-use groups (i.e. older adults, health workers, persons with comorbidities) 4-6 months after the completion of the primary series. If more than 6 months have elapsed since the completion of the primary series, the booster dose should be given at the earliest opportunity.
Once high booster dose coverage has been achieved in the highest priority-use group, countries may also consider a booster for other lower priority-use groups.
WHO has not yet determined the need for and timing of booster doses for persons below 12 years of age, except for immunocompromised children.
Second booster dose:
WHO recommends considering a second booster dose 4-6 months after the first booster dose for all older persons (age-specific cutoff defined by countries), all persons with moderate and severe immunocompromising conditions -regardless of age-, adults with comorbidities that put them at higher risk of severe disease, pregnant women, and health workers [WHO, 2022 ].
FDA recommends a second booster dose for persons 50 years of age and older and immunocompromised individuals from 18 years of age, provided at least after 4 months of the first booster dose [FDA, 2022 ].
EMA recommends second booster dose for persons 60 years of age and older and medically vulnerable individuals provided at least after 4 months of the first booster dose [EMA, 2022 ].
Heterologous schedule [WHO, 2022 ]
WHO supports a flexible approach to use different COVID-19 vaccine platforms for different doses (heterologous schedule) and considers two doses of any EUL COVID-19 vaccine to constitute a complete primary series.
For persons aged 12 and older, a 50 μg dose of the Moderna COVID-19 vaccine may be used as a booster dose following a completed primary series from any other EUL COVID-19 vaccine platform.
Heterologous vaccination should only be implemented with careful consideration of current vaccine supply, vaccine supply projections, and other access considerations, along with the potential benefits and risks of the specific products being used.
Vaccination schedule for immunocompromised persons [WHO, 2022 ]
WHO recommends an extended primary series including an additional (third) full 100 µg dose for immunocompromised persons.
An additional (third) dose should be given 1-3 months after the second dose in the standard primary series in order to increase protection as quickly as possible in immunocompromised persons.
A first and second booster dose (fourth and fifth doses) given 4-6 months after the previous dose is recommended for all immunocompromised persons.
Adapted Moderna COVID-19 vaccines
Spikevax bivalent (original + omicron BA.1)
Spikevax bivalent (original + omicron BA.1) is administered as a single booster dose (0.25 mL for persons aged 6-11 years, and 0.5 mL for persons aged ≥12 years) after three months of the primary series or monovalent booster [EMA, 2022 ].
The pharmaceutical form is a dispersion for intramuscular injection provided in a multidose vial (each 0.5 mL dose containing 25 μg of elasomeran and 25 μg of imelasomeran)
The preferred site of injection is the deltoid muscle of the upper arm.
Spikevax bivalent (original + omicron BA.4/BA.5)
EMA recommends to administer Spikevax bivalent (original + omicron BA.4/BA.5) as a single booster dose (0.5 mL) for persons aged 12 years and older after three months of the primary series or monovalent booster [EMA, 2022 ].
FDA recommends to administer Spikevax bivalent (original + omicron BA.4/BA.5) as a single booster dose (0.2 mL for persons 6 months to 5 years of age, 0.25 mL for persons aged 6-11 years, and 0.5 mL for persons aged ≥12 years) after two months of the primary series or monovalent booster [FDA, 2022 ].
The pharmaceutical form is a dispersion for intramuscular injection provided in a multidose vial (each 0.5 mL dose containing 50 μg)
The preferred site of injection is the deltoid muscle of the upper arm.
Indications and contraindications
Moderna COVID-19 vaccine (original strain)
Indications
Moderna COVID-19 vaccine is indicated for individuals 6 months of age and older [WHO, 2022 ].
For prioritization by age and other considerations, refer to the WHO Prioritization Roadmap [WHO, 2022 ]
WHO recommends the use of Moderna COVID-19 vaccine in pregnant individuals.
WHO does not recommend pregnancy testing prior to vaccination. WHO does not recommend delaying pregnancy or terminating pregnancy because of vaccination [WHO, 2022 ].
Contraindications
Moderna COVID-19 vaccine is contraindicated in individuals with a known history of a severe allergic reaction to any component of Moderna COVID-19 vaccine [WHO, 2022 ]. (See the list of ingredients under 'General characteristics' in the extended version).
The second dose of the vaccine should NOT BE GIVEN to those who have experienced anaphylaxis to the first dose of Moderna COVID-19 vaccine [WHO, 2022 ].
Adapted Moderna COVID-19 vaccines
Spikevax bivalent (original + omicron BA.1)
Indications
Spikevax bivalent (original + omicron BA.1) is indicated as a booster dose for individuals 6 years of age and older [EMA, 2022 ].
Contraindications
Spikevax bivalent (original + omicron BA.1) is contraindicated in individuals with a known history of a severe allergic reaction to any component of the vaccine [EMA, 2022 ]. (See the list of ingredients under 'General characteristics' in the extended version).
Spikevax bivalent (original + omicron BA.4/BA.5)
Indications
EMA recommends to administer Spikevax bivalent (original + omicron BA.4/BA.5) as a booster dose for individuals 12 years of age and older [EMA, 2022 ].
FDA recommends to administer Spikevax bivalent (original + omicron BA.4/BA.5) as a booster dose for individuals 6 months of age and older [FDA, 2022 ].
Contraindications
Spikevax bivalent (original + omicron BA.4/BA.5) is contraindicated in individuals with a known history of a severe allergic reaction to any component of the vaccine [FDA, 2022 ]. (See the list of ingredients under 'General characteristics' in the extended version).
Precautions
Moderna COVID-19 vaccine (original strain)
Allergic reactions [WHO, 2022 ].
A history of anaphylaxis to any other vaccine or injectable therapy (i.e. intramuscular, intravenous, or subcutaneous vaccines or therapies) is not a contraindication to vaccination. For such persons, a risk assessment should be conducted by a health professional. The vaccine should be administered only in settings where anaphylaxis can be treated. Such persons should be observed for 30 minutes after vaccination.
Individuals with an immediate non-anaphylactic allergic reaction to the first dose (such as urticaria, angioedema or respiratory symptoms, that occur within 4 hours of administration) should not receive additional doses, unless recommended after review by a health professional. Subject to individual risk–benefit assessment, Moderna COVID-19 vaccine could be provided under close medical supervision if it is the only available option for people at high risk of severe COVID-19.
The vial stoppers are not made with natural rubber latex, and there is no contraindication or precaution to vaccination for persons with a latex allergy. In addition, as Moderna COVID-19 vaccine does not contain eggs or gelatine, there is no contraindication or precaution to vaccination for persons with allergies to any food substances.
Myocarditis [WHO, 2022 ].
Myocarditis is a rare adverse event that has been reported after receipt of mRNA COVID-19 vaccines. The observed risk is highest in males aged 18–39 years (with the highest risk in males aged 18–24 years), and highest within a few days after the second dose.
Vaccinated individuals should be instructed to seek immediate medical attention if they develop symptoms indicative of myocarditis or pericarditis, such as new onset and persisting chest pain, shortness of breath, or palpitations following vaccination. It is important to rule out other potential causes of myocarditis and pericarditis, including COVID-19 infection and other viral aetiologies.
Individuals who develop myocarditis or pericarditis after a dose of Moderna COVID-19 vaccine should generally not receive additional doses of any COVID-19 vaccine, unless recommended after review by a health professional with specialist expertise [WHO, 2022 ].
Pregnancy [WHO, 2022 ]
WHO recommends the use of Moderna COVID-19 vaccine in pregnant individuals.
WHO does not recommend pregnancy testing prior to vaccination. WHO does not recommend delaying pregnancy or terminating pregnancy because of vaccination.
Breastfeeding [WHO, 2022 ].
Vaccine effectiveness is expected to be similar in breastfeeding women as in other adults. As Moderna COVID-19 vaccine is not a live virus vaccine and the mRNA does not enter the nucleus of the cell and is degraded quickly, it is biologically and clinically unlikely to pose a risk to the nursing infant. Several small studies show that mRNA vaccine-elicited antibodies are found in breast milk, which might help protect breastfeeding infants.
On the basis of these considerations, WHO recommends the use of Moderna COVID-19 vaccine in breastfeeding women.
WHO does not recommend discontinuing breastfeeding because of vaccination.
Children and adolescents [WHO, 2022 ].
The priority remains to prevent deaths by achieving high vaccine coverage (primary series and boosters) in the highest and high priority-use groups. It is of utmost importance for children to continue to receive the recommended childhood vaccines for other infectious diseases.
Older persons [WHO, 2022 ].
Vaccination is recommended for older persons without an upper age limit
Persons living with HIV [WHO, 2022 ].
Persons living with HIV who are stable on antiretroviral therapy should be vaccinated. It is not necessary to test for HIV infection before administration of the vaccine.
Persons with previous SARS-CoV-2 infection [WHO, 2022 ].
Vaccination may be offered regardless of a person’s history of symptomatic or asymptomatic SARS-CoV-2 infection.
The optimal time interval between a natural infection and vaccination is not yet known, but an interval of 3 months could be considered.
Persons with current acute COVID-19 [WHO, 2022 ].
Persons with acute PCR-confirmed COVID-19, including between doses, should not be vaccinated until after they have recovered from acute illness and the criteria for discontinuation of isolation have been met.
Persons who previously received passive antibody therapy for COVID-19[WHO, 2022 ]
Although some reduction in vaccine-induced antibody titers has been observed in this group, the balance of benefits versus risks favors vaccination.
Other precautions
Vaccination should be postponed in individuals with an acute febrile illness (body temperature over 38.5 °C) or acute infection [WHO, 2022 ].
A few cases of capillary leak syndrome (CLS) flare-ups have been reported within the first days after the vaccination with Spikevax (original). In individuals with a history of CLS, vaccination should be assessed by appropriate medical experts [EMA, 2022 ].
Co-administration with other vaccines
For adults, based on several co-administration studies, COVID-19 vaccines may be administered concomitantly or at any time before or after other adult vaccines, including: live attenuated vaccines, inactivated, adjuvanted, or non-adjuvanted vaccines.
When administered concomitantly, the vaccines should be injected at separate sites, preferably different extremities [WHO, 2022 ].
Inactivated influenza vaccine [WHO, 2022 ].
WHO recommends that countries consider co-administration of COVID-19 vaccines with seasonal influenza vaccines, whenever feasible, dependent on seasonality.
Adapted Moderna COVID-19 vaccines
Spikevax bivalent (original + omicron BA.1)
Allergic reactions [EMA, 2022 ].
Events of anaphylactic reactions have been reported after receiving Spikevax (original). Appropriate medical treatment and supervision should be available in case of an anaphylactic reaction following the administration of Spikevax bivalent (original + omicron BA.1).
Close observation for at least 15 minutes is recommended following vaccination
Myocarditis and pericarditis [EMA, 2022 ].
There is an increased risk of myocarditis and pericarditis after vaccination with Spikevax (original), observed more often after the second dose, and in younger males.
Pregnancy [EMA, 2022 ]
There are no available data regarding the use of Spikevax bivalent (original + omicron BA.1) during pregnancy.
However, a large amount of observational data from vaccination with Spikevax during the second and third trimesters have not shown an increase in adverse pregnancy outcomes.
Breastfeeding [EMA, 2022 ].
There are no available data regarding the use of Spikevax bivalent (original + omicron BA.1) during breastfeeding.
However, observational data from vaccination with Spikevax from breastfeeding women have not shown an increase in adverse effects in breastfed infants.
Immunocompromised persons [EMA, 2022 ].
The efficacy and safety of this vaccine have not been assessed in immunocompromised persons. The efficacy of Spikevax bivalent (original + omicron BA.1) may be lower in these individuals.
Other precautions
Vaccination should be postponed in individuals with an acute febrile illness or acute infection [EMA, 2022 ].
A few cases of capillary leak syndrome (CLS) flare-ups have been reported within the first days after the vaccination with Spikevax (original). In individuals with a history of CLS, vaccination should be assessed by appropriate medical experts [EMA, 2022 ].
As with other intramuscular injections, the vaccine should be given with caution in individuals with bleeding disorders or other conditions that increase the risk of bleeding, such as anticoagulant therapy, thrombocytopenia and hemophilia [EMA, 2022 ].
Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress-related reactions may occur in association with the vaccination process itself [EMA, 2022 ].
Spikevax bivalent (original + omicron BA.4/BA.5)
Allergic reactions [FDA, 2022 ].
Appropriate medical treatment should be available in case of an anaphylactic reaction following the administration of Spikevax bivalent (original + omicron BA.4/BA.5).
Close observation for at least 15 minutes is recommended following vaccination
Myocarditis and pericarditis [FDA, 2022 ].
There is an increased risk of myocarditis and pericarditis after vaccination with Spikevax (original), observed more often after the second dose or first booster, and in younger males (18 through 24 years of age).
Pregnancy [FDA, 2022 ]
There are no available data regarding the use of Spikevax bivalent (original + omicron BA.4/BA.5) during pregnancy.
Breastfeeding [FDA, 2022 ].
There are no available data regarding the use of Spikevax bivalent (original + omicron BA.4/BA.5) during breastfeeding.
Immunocompromised persons [FDA, 2022 ].
The efficacy and safety of this vaccine have not been assessed in immunocompromised persons. The efficacy of Spikevax bivalent (original + omicron BA.4/BA.5) may be lower in these individuals.
Other precautions
Anxiety-related reactions, including vasovagal reactions (syncope) may occur in association with the vaccination process itself [FDA, 2022 ].
Storage and logistics
Moderna COVID-19 vaccine (original strain)
Storage
The Moderna COVID-19 vaccine is presented as 1. Spikevax 100 mcg (light blue border label), 2. Spikevax 50 mcg (purple border label), 3. Spikevax 25 mcg (magenta border label) [WHO, 2021 ], [FDA, 2022 ].
All presentations are provided frozen and stored at -50°C to -15°C (-58°F to 5°F) for up to 9 months [FDA, 2022 ].
Within the 9 months of shelf life, the vaccine can be stored 30 days at 2°-8°C [WHO, 2022 ].
Do not refreeze once thawed.
Keep vaccine vials in their box and place them in the storage unit.
Store in the original carton to protect from light.
Administration logistics [WHO, 2021 ]
Remove the required number of the vial(s) from storage and thaw each vial before use.
Keep the vial for 2 hours and 30 minutes in the refrigerator from 2°C to 8°C (36°F and 46°F), after, let vial sits for 15 minutes before administering, or, maintained 1 hour at room temperature from 15°C to 25°C [Moderna Inc., 2020 ].
The vaccine should be inspected visually for particulate matter and discoloration prior to administration.
The vial should be inspected visually for cracks or any abnormalities, such as evidence of tampering prior to administration. If any of these should exist, do not administer the vaccine.
Swirl the vial gently after thawing and before each withdrawal. Do not shake or dilute.
Use a sterile needle and syringe to extract a single dose from the multidose vial.
Administration
1. Using aseptic technique, clean the vial stopper with a single-use antiseptic swab.
2. Use a 3 ml reuse prevention syringe (RUP) or a 5 mL RUP syringe, and a 21G or narrower needle.
3. Gently invert the vial to mix, and withdraw the dose according to the targeted group. If the amount of vaccine remaining in the vial cannot provide a full dose, discard the vial and the remaining volume.
4. Administer the vaccine intramuscularly, preferably into the deltoid muscle. Do not administer the vaccine intravascularly, subcutaneously, or intradermally.
Storage after first puncture
After taking the first dose from the multidose vial, the vial should be used within a maximum of 6 hours (stored at 2°C to 8°C [36°F to 46°F]) or discarded at the end of the immunization session, whichever comes first [WHO, 2022 ].
Record the date and time the vial should be discarded.
To improve traceability, the name and batch number of the administered product should be clearly recorded [WHO, 2021 ].
Disposal
Due to the high risk that discarded vials of COVID-19 vaccines may be recovered, it is essential that they are guaranteed to be safely disposed of at the site of use; or study the possibility of applying reverse logistics, if the safe treatment and disposal of vaccine residues cannot be guaranteed, so that they are transferred to the place established for that purpose. Otherwise, consider the possibility that the discarded vaccine vials are shredded, if there is a safe way to do so [WHO, 2021 ].
Adapted Moderna COVID-19 vaccines
Spikevax bivalent (original + omicron BA.1)
Storage [EMA, 2022 ].
Spikevax bivalent (original + omicron BA.1) is provided as a frozen dispersion for intramuscular injection stored at -50°C to -15°C (-58°F to 5°F) for up to 9 months [EMA, 2022 ]
Unopened vials can be stored for up to 30 days refrigerated at 2° to 8°C.
Do not refreeze once thawed.
Keep vaccine vials in their box and place them in the storage unit.
Store in the original carton to protect from light.
Administration logistics [EMA, 2022 ]
Remove the required number of the vial(s) from storage and thaw each vial before use.
Keep the vial for 2 hours and 30 minutes in the refrigerator from 2°C to 8°C (36°F and 46°F), after let vial sits at room temperature for 15 minutes before administering, or, maintained 1 hour at room temperature from 15° to 25°C.
The vaccine should be inspected visually for particulate matter and discoloration prior to administration.
The vial should be inspected visually for cracks or any abnormalities, such as evidence of tampering prior to administration. If any of these should exist, do not administer the vaccine.
Swirl the vial gently after thawing and before each withdrawal. Do not shake or dilute.
Use a sterile needle and syringe to extract a single dose from the multidose vial.
Administration [EMA, 2022 ]
1. Using aseptic technique, clean the vial stopper with a single-use antiseptic swab.
2. Use a 3 ml reuse prevention syringe (RUP) or a 5 mL RUP syringe, and a 21G or narrower needle.
3. Gently invert the vial to mix, and withdraw the dose according to the targeted group. If the amount of vaccine remaining in the vial cannot provide a full dose, discard the vial and the remaining volume.
4. Administer the vaccine intramuscularly, preferably into the deltoid muscle. Do not administer the vaccine intravascularly, subcutaneously, or intradermally.
Storage after first puncture [EMA, 2022 ]
After taking the first dose from the multidose vial, the vial should be used within a maximum of 19 hours (stored at 2°C to 8°C [36°F to 46°F]).
Record the date and time the vial should be discarded.
To improve traceability, the name and batch number of the administered product should be clearly recorded.
Disposal
Due to the high risk that discarded vials of COVID-19 vaccines may be recovered, it is essential that they are guaranteed to be safely disposed of at the site of use; or study the possibility of applying reverse logistics, if the safe treatment and disposal of vaccine residues cannot be guaranteed, so that they are transferred to the place established for that purpose. Otherwise, consider the possibility that the discarded vaccine vials are shredded, if there is a safe way to do so [WHO, 2021 ].
Spikevax bivalent (original + omicron BA.4/BA.5)
Storage [EMA, 2022 ].
Spikevax bivalent (original + omicron BA.4/BA.5) is provided as a frozen dispersion for intramuscular injection stored at -50°C to -15°C (-58°F to 5°F) for up to 9 months [EMA, 2022 ]
Unopened vials can be stored for up to 30 days refrigerated at 2° to 8°C.
Do not refreeze once thawed.
Keep vaccine vials in their box and place them in the storage unit.
Store in the original carton to protect from light.
Administration logistics [EMA, 2022 ]
Remove the required number of the vial(s) from storage and thaw each vial before use.
Keep the vial for 2 hours and 30 minutes in the refrigerator from 2°C to 8°C (36°F and 46°F), after, let vial sits for 15 minutes before administering, or, maintained 1 hour at room temperature from 15°C to 25°C.
The vaccine should be inspected visually for particulate matter and discoloration prior to administration.
The vial should be inspected visually for cracks or any abnormalities, such as evidence of tampering prior to administration. If any of these should exist, do not administer the vaccine.
Swirl the vial gently after thawing and before each withdrawal. Do not shake or dilute.
Use a sterile needle and syringe to extract a single dose from the multidose vial.
Administration [EMA, 2022 ]
1. Using aseptic technique, clean the vial stopper with a single-use antiseptic swab.
2. Use a 3 ml reuse prevention syringe (RUP) or a 5 mL RUP syringe, and a 21G or narrower needle.
3. Gently invert the vial to mix, and withdraw the dose according to the targeted group. If the amount of vaccine remaining in the vial cannot provide a full dose, discard the vial and the remaining volume.
4. Administer the vaccine intramuscularly, preferably into the deltoid muscle. Do not administer the vaccine intravascularly, subcutaneously, or intradermally.
Storage after first puncture [EMA, 2022 ]
After taking the first dose from the multidose vial, the vial should be used within a maximum of 19 hours (stored at 2°C to 8°C [36°F to 46°F]).
Record the date and time the vial should be discarded.
To improve traceability, the name and batch number of the administered product should be clearly recorded.
Disposal
Due to the high risk that discarded vials of COVID-19 vaccines may be recovered, it is essential that they are guaranteed to be safely disposed of at the site of use; or study the possibility of applying reverse logistics, if the safe treatment and disposal of vaccine residues cannot be guaranteed, so that they are transferred to the place established for that purpose. Otherwise, consider the possibility that the discarded vaccine vials are shredded, if there is a safe way to do so [WHO, 2021 ].
Clinical studies - general characteristics
The following randomized clinical trials have reported vaccine efficacy and/or safety data:
Phase 1:
The 20-0003 trial, (NCT04283461, [National Institute of Allergy and Infectious Diseases (NIAID), 2020 ]), conducted in the United States, initiated in April 2020, included 45 healthy adults, 18 to 55 years of age, who received two Moderna vaccines, 28 days apart, in doses of 25 μg, 100 μg, or 250 μg with 15 participants in each dose group. The trial was expanded to include 40 older adults, who were stratified by age (56 to 70 years or ≥71 years). All participants were sequentially assigned to receive two 25-μg or 100-μg doses of vaccine administered 28 days apart [Jackson LA, 2020 ], [Widge AT, 2021 ], [Greaney AJ, 2021 ], [Kai Wu, 2021 ], [Anderson EJ, 2020 ].
The 21-0002 trial (NCT04785144, [National Institute of Allergy and Infectious Diseases (NIAID), 2021 ]), conducted in the United States, started in March 2021, included 135 participants 18 years of age and older. Three mRNA booster vaccines were evaluated in participants who received their primary two-dose series as part of trial 20–0003. Participants were matched by age (18 to 55 years, 56 to 70 years, and ≥71 years) and received a primary series of two mRNA-1273 vaccines 28 days apart at doses of 25, 50, 100, or 250 mcg [Anderson E, 2022 ].
Phase 1/2:
The trial by Chuang CH et al. (NCT05132855, [Chang Gung Memorial Hospital, 2021 ]) conducted in Taiwan, started in November 2021, included 340 health workers who had received two doses of AstraZeneca. Participants, 90 days after the second dose, received one of four vaccines: Pfizer, Moderna half-dose, Moderna, and MVC-COV1901 [Chih-Hsien Chuang, 2022 ].
The COVAIL trial (NCT05289037, [National Institute of Allergy and Infectious Diseases (NIAID), 2022 ]), conducted in the United States, started in March 2022, included 597 healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single booster. Participants were randomized to one of six Moderna COVID-19 mRNA vaccine arms (50 mcg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+ Delta, Omicron BA.1 monovalent and Omicron BA.1+Prototype [Angela R Branche, 2022 ].
Phase 2:
The mRNA-1273-P201 trial (NCT04405076, [ModernaTX, Inc., 2020 ]) conducted in the United States, initiated in May 2020, included 600 participants 18 years of age and older. Participants were stratified into two age cohorts (≥18-<55 and ≥55 years; 300 in each group) and randomly assigned (1:1:1) to 50 or 100 µg of the Moderna vaccine, or placebo given as two intramuscular injections 28 days apart. [Chu L, 2021 ]
The COV-BOOST trial (ISRCTN73765130, [University Hospital Southampton NHS Foundation Trust, 2021 ]), conducted in the UK since June 2021 included 2,878 participants who were randomized 1:1:1:1 into Group A, 1:1:1:1:1 in group B and 1:1:1:1 in group C to receive an experimental or control vaccine as booster dose after a primary schedule of the AstraZeneca or Pfizer-BioNTech COVID-19 vaccine. The intervention was administered as follows: group A received Novavax, half-dose Novavax, AstraZeneca, or control quadrivalent meningococcal conjugate vaccine (MenACWY); group B received Pfizer, Valneva, half-dose Valneva, Janssen, or MenACWY; group C received Moderna, CureVac, half-dose Pfizer, or MenACWY. [Munro, Alasdair P S, 2021 ], [Munro APS, 2022 ], [Liu X, 2022 ]
The trial conducted by Bonelli M et al (2021-002348-57 [Medical University of Vienna, 2021 ]) in Austria, started in May 2021, included 60 adults with chronic inflammatory rheumatic or neurological diseases under current treatment with rituximab randomized in a 1:1 ratio based on in the presence or absence of peripheral B lymphocytes to receive a third dose of an mRNA vaccine (Pfizer or Moderna, according to their initial vaccination compound) or a third vaccination with a vector COVID-19 vaccine (AstraZeneca). [Michael Bonelli, 2021 ], [Bonelli M, 2022 ]
The BOOST-TX trial (NCT04614948, [Janssen Vaccines & Prevention B.V., 2020 ]) conducted in Austria since May 2021 included 197 adult kidney transplant recipients after 2 months of receiving an mRNA vaccine. Participants received a third dose of the BNT162b2 vaccine (n=99) or nRNA-1273 vaccine (n=98). In the three-month follow-up of the trial, 201 kidney transplant recipients were included after two doses of an mRNA vaccine: 101 received the third dose of the same mRNA vaccine and 100 received the third dose of the Janssen vaccine. [Heinzel A, 2022 ], [Reindl-Schwaighofer R, 2021 ]
Phase 2/3:
The TeenCove trial (NCT04649151, [ModernaTX, Inc., 2020 ]), conducted in the United States and started in November 2020, included 3,732 adolescent participants between the ages of 12 and 17 who were randomized in a 2:1 ratio to receive two injections of the Moderna vaccine ( 100 μg each) or placebo, administered 28 days apart. [Ali K, 2021 ]
The KidCOVE trial (NCT04796896 [ModernaTX, Inc., 2021 ]), conducted in the United States since March 2021, included 13,574 children between 6 months and 11 years of age. Part 1 of the trial was conducted for dose selection. In part 2, children were randomly assigned in a 3:1 ratio to receive two injections of Moderna (50 μg for children 6 to 11 years of age; and 25 μg for those aged 6 months to 5 years) or a placebo, given 28 days apart [Creech CB, 2022 ] [Anderson EJ, 2022 ].
The mRNA-1273-P205 trial (NCT04927065 [ModernaTX, Inc., 2021 ]) conducted in the United States, initiated in June 2021, included 896 adults fully vaccinated with Moderna who received a single booster dose of the bivalent Omicron BA.1-containing vaccine (mRNA-1273.211), 50 µg (n = 300) or 100µg (n = 595) of the Moderna (mRNA-1273) vaccine between 8.7 and 9.7 months after the primary schedule. [Chalkias S, 2022 ], [Chalkias S, 2022 ]
Safety and immunogenicity of the bivalent Omicron BA.4/BA.5-containing vaccine (mRNA-1273.222) was assessed in participants who received 50µg of the Moderna (mRNA-1273) vaccine (n=376) or mRNA-1273.222 (n=511) as second booster doses. [Spyros Chalkias, 2022 ].
The mRNA-1273-P305 trial (NCT05249829 [ModernaTX, Inc., 2022 ]), conducted in the United Kingdom, starting in February 2022. In the first part of the study, 719 participants received the mRNA-1273.529 (n=362) or mRNA-1273 (n=357) vaccine; in the second part, 2813 received mRNA-1273.214 (n=1418) or mRNA-1273 (n=1395).
Participants (individuals over 16 years of age) had previously received 2 doses of any licensed Covid-19 vaccine with or without an mRNA booster. [Lee, I. T., 2023 ]
Phase 3:
The COVE trial (NCT04470427, [ModernaTX, Inc., 2020 ]) conducted in the United States, initiated in July 2020, included 30,420 participants aged 18 years and older. Participants received either two doses of the Moderna vaccine (100 μg) or the placebo vaccine, administered 28 days apart [Pajon R, 2022 ], [Rojas C, 2022 ], [Gilbert PB, 2021 ], [El Sahly HM, 2021 ], [Baden LR, 2021 ], [Baden LR, 2021 ], [El Sahly HM, 2022 ].
The PRIBIVAC trial (NCT05142319, [Tan Tock Seng Hospital, 2021 ]) conducted in Singapur, initiated in December 2021, included 600 adults receiving four different COVID-19 booster schedules. Participants who received a BNT162b2 (Pfizer COVID-19 vaccine) primary schedule (n=100) were randomized 1:1 to either homologous BNT162b2 booster or heterologous mRNA-1273 (Moderna) booster [Poh XY, 2022 ], [Poh X, 2022 ], [Poh XY, 2022 ].
Phase 4:
The trial by Hall VG et al (NCT04885907, [University Health Network, Toronto, 2021 ]) conducted in Canada, started in May 2021, included 120 transplant patients who had received two doses of the Moderna vaccine at 0 and 1 month. Participants were randomized 1:1 to receive a third dose of Moderna COVID-19 vaccine or placebo 3 months after the primary vaccination schedule. [Kumar D, 2021 ], [Hall VG, 2021 ].
The RECOVAC trial (NCT05030974, [University Medical Center Groningen, 2021 ]) conducted in the Netherlands started in October 2021 and enrolled 333 kidney transplant recipients (KTR) who did not seroconvert after an initial mRNA vaccine schedule: 230 KTRs were randomly assigned in a 1:1:1 manner to receive 100 μg mRNA-1273, 2 × 100 μg mRNA-1273, or Ad26.COV2-S vaccination. In addition, 103 KTRs receiving 100 μg mRNA-1273, were randomly assigned 1:1 to continue (mycophenolate mofetil+) or discontinue (mycophenolate mofetil-) mycophenolate mofetil or mycophenolic acid treatment for 2 weeks. [Kho MML, 2022 ]
Other trials reporting data:
The SWITCH trial (NCT04614948, [Erasmus Medical Center, 2021 ]) conducted in the Netherlands, initiated June 2021 and September 2022, included 461 participants over the age of 18, who were randomized 1:1:1:1 to not receiving a booster, receiving a Janssen booster, receiving a Moderna booster, or receiving a Pfizer–BioNTech booster. [Sablerolles RSG, 2022 ]
The SWITCH ON trial (NCT05471440, [Erasmus Medical Center, 2022 ]) conducted in the Netherlands since August 2022, included 187 participants who had received a primary Janssen COVID-19 vaccination or an mRNA primary schedule, randomized to receive an Omicron-containing bivalent booster (BNT162b2 Omicron BA.1 or mRNA-1273.214) [Ngoc Tan, 2022 ], [Tan NH, 2022 ].
Vaccine efficacy and effectiveness
Efficacy of preclinical studies on the vaccine
The immunogenicity of the Moderna COVID-19 vaccine was tested in non-human primates that received 10 or 100 µg of mRNA-1273 or no vaccine. The mRNA-1273 vaccine candidate induced robust antibody responses with ID50 GMTs higher in the 100 μg dose group (3481) compared to the 10 μg dose group (501). Peak subgenomic RNA levels during days 2 through 7 were significantly lower in both the 100 μg dose group and the 10 μg dose group than the control group, in both bronchoalveolar fluid specimens (BAL) and nasal swab samples. Furthermore, total RNA levels were significantly lower in BAL fluid in both dose groups than in the control group [Corbett KS, 2020 ].
Efficacy of the vaccine in clinical trials
Main immunogenicity outcomes
mRNA-1273-P201 (NCT04405076) was a phase 2 trial sponsored by ModernaTX, Inc. and conducted in the United States. The trial included healthy participants ≥18 years of age. The sample size was 600 (2 cohorts of 300). Participants were randomized 1: 1 to receive Moderna COVID-19 vaccine in doses of 50 µg, 100 µg or placebo. The results showed that in both vaccination schemes of mRNA-1273 vaccine, the geometric mean titers increased 28 days after the first dose. Furthermore, 14 days after the second dose (day 43), the geometric mean titers improved significantly, 1733 (1611-1865) µg/ml in the 50 µg group and 1909 (1849-1971) µg/ml in 100 µg group in young adults, while in older adults, mean titers were 1827 (1722 -1938) µg/ml in the 50 µg group and 1686 [1521-1869] µg/ml in the 100 µg group of mRNA-1273 vaccine [Chu L, 2021 ].
In the preliminary report of the phase 1 study [Jackson LA, 2020 ], it was reported that the vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. In this dose-escalation trial, in 45 adults 18 to 55 years of age antibody responses were higher with higher doses after a first vaccination, and serum neutralizing activity was detected after second vaccination.
Main efficacy outcomes of Moderna COVID-19 vaccine
Key messages
Moderna COVID-19 vaccine reduces the risk of contracting COVID-19
Moderna COVID-19 vaccine reduces the risk of contracting severe COVID-19
Contracting COVID-19 (measured at least 14 days after the second injection, with a median follow-up of 5.3 months after 2nd dose)
The relative risk of contracting COVID-19 in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.07 (95% CI 0.06 to 0.1). This means Moderna COVID-19 vaccine reduced the risk of contracting COVID-19 by 93%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19. Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 751 people not receiving Moderna COVID-19 vaccine out of 14164 presented this outcome (49 per 1000) versus 55 out of 14287 in the group that did receive it (4 per 1000). In other words, 45 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 4.5%, or that the intervention reduced the risk of contracting COVID-19 by 4.5 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTB is 22. Which means that 22 people need to receive the vaccine for one of them to not contract COVID-19.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.
Contracting severe COVID-19 (measured at least 14 days after the second injection, with a median follow-up of 5.3 months after 2nd dose)
The relative risk of contracting severe COVID-19 in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.02 (95% CI 0 to 0.08). This means Moderna COVID-19 vaccine reduced the risk of contracting severe COVID-19 by 98%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting severe COVID-19. Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 106 people not receiving Moderna COVID-19 vaccine out of 14164 presented this outcome (7 per 1000) versus 2 out of 14287 in the group that did receive it (0 per 1000). In other words, 7 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 0.7%, or that the intervention reduced the risk of contracting severe COVID-19 by 0.7 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTB is 143. Which means that 143 people need to receive the vaccine for one of them to not contract severe COVID-19.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.
Mortality
The existing evidence does not allow to assess the impact of Moderna COVID-19 vaccine on the risk of death attributable to COVID-19. The information provided by randomized trials was not adequately powered to estimate a difference in this outcome. Deaths can occur in the intervention and control group for reasons unrelated to COVID-19 or the vaccine. Establishing that there is a reduction (or increase) in the risk of death attributable to Moderna COVID-19 vaccine would require trials with a higher statistical power.
Efficacy of the vaccine in subgroups
Contracting COVID-19 (6-11y) (measured at least 14 days after the first injection)
The relative risk of contracting COVID-19 (6-11y) in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.12 (95% CI 0.05 to 0.28). This means Moderna COVID-19 vaccine reduced the risk of contracting COVID-19 (6-11y) by 88%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19 (6-11y). Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 7 people not receiving Moderna COVID-19 vaccine out of 2887 presented this outcome (20 per 1000) versus 18 out of 880 in the group that did receive it (2 per 1000). In other words, 18 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 1.8%, or that the intervention reduced the risk of contracting COVID-19 (6-11y) by 1.8 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNT is 56. Which means that 250 people need to receive the vaccine for one of them to not contract COVID-19.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.
Contracting COVID-19 after second dose (12-17y) (measured at least 14 days after the second injection)
The relative risk of Contracting COVID-19 after second dose (12-17y) in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.06 (95% CI 0 to 1.03). This means Moderna COVID-19 vaccine reduced the risk of Contracting COVID-19 after second dose (12-17y) by 94%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: Contracting COVID-19 after second dose (12-17y). Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, people not receiving Moderna COVID-19 vaccine out of presented this outcome (3 per 1000) versus out of in the group that did receive it (0 per 1000). In other words, 3 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 0.3%, or that the intervention reduced the risk of Contracting COVID-19 after second dose (12-17y) by 0.3 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTB is 333. Which means that 250 people need to receive the vaccine for one of them to not contract COVID-19.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as moderate. The certainty of the evidence is based in the following judgments: Risk of bias: no concerns; Inconsistency: no concerns; Indirectness: no concerns; Imprecision: the information provides from a small sample; Publication bias: no concerns.
Contracting COVID-19 (>65y) (measured at least 14 days after the second injection)
The relative risk of Contracting COVID-19 (>65y) in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.11 (95% CI 0.05 to 0.21). This means Moderna COVID-19 vaccine reduced the risk of Contracting COVID-19 (>65y) by 89%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: Contracting COVID-19 (>65y). Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 81 people not receiving Moderna COVID-19 vaccine out of 2898 presented this outcome (8 per 1000) versus 9 out of 2990 in the group that did receive it (1 per 1000). In other words, 7 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 0.7%, or that the intervention reduced the risk of Contracting COVID-19 (>65y) by 0.7 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTB is 143. Which means that 143 people need to receive the vaccine for one of them to not contract COVID-19.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as moderate. The certainty of the evidence is based in the following judgments: Risk of bias: no concerns; Inconsistency: no concerns; Indirectness: no concerns; Imprecision: the information provides from a small sample; Publication bias: no concerns.
Contracting COVID-19 (>75y) (measured at least 14 days after the second injection)
The relative risk of Contracting COVID-19 (>75y) in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.03 (95% CI 0 to 0.46). This means Moderna COVID-19 vaccine reduced the risk of Contracting COVID-19 (>75y) by 97%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: Contracting COVID-19 (>75y). Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 19 people not receiving Moderna COVID-19 vaccine out of 697 presented this outcome (8 per 1000) versus 0 out of 636 in the group that did receive it (0 per 1000). In other words, 8 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 0.8%, or that the intervention reduced the risk of Contracting COVID-19 (>75y) by 0.8 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTB is 125. Which means that 125 people need to receive the vaccine for one of them to not contract COVID-19.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as moderate. The certainty of the evidence is based in the following judgments: Risk of bias: no concerns; Inconsistency: no concerns; Indirectness: no concerns; Imprecision: the information provides from a small sample; Publication bias: no concerns.
Contracting COVID-19 (men subgroup) (measured at least 14 days after the second injection)
The relative risk of contracting COVID-19 in men in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.08 (95% CI 0.06 to 0.12). This means Moderna COVID-19 vaccine reduced the risk of contracting COVID-19 in men by 92%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19 in men. Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 378 people not receiving Moderna COVID-19 vaccine out of 7494 presented this outcome (50 per 1000) versus 30 out of 7439 in the group that did receive it (4 per 1000). In other words, 46 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 4.6%, or that the intervention reduced the risk of contracting COVID-19 in men by 4.6 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTB is 22. Which means that 22 people need to receive the vaccine for one of them to not contract COVID-19.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as moderate. The certainty of the evidence is based in the following judgments: Risk of bias: no concerns; Inconsistency: no concerns; Indirectness: no concerns; Imprecision: the information provides from a small sample; Publication bias: no concerns.
Contracting COVID-19 (women subgroup) (measured at least 14 days after the second injection)
The relative risk of contracting COVID-19 in women in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.07 (95% CI 0.04 to 0.1). This means Moderna COVID-19 vaccine reduced the risk of contracting COVID-19 in women by 93%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19 in women. Comparison: Moderna COVID-19 vaccine versus
In the trial identified in this review, 366 people not receiving Moderna COVID-19 vaccine out of 6670 presented this outcome (55 per 1000) versus 25 out of 6848 in the group that did receive it (4 per 1000). In other words, 51 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 5.1%, or that the intervention reduced the risk of contracting COVID-19 in women by 5.1 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTB is 20. Which means that 20 people need to receive the vaccine for one of them to not contract COVID-19.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as moderate. The certainty of the evidence is based in the following judgments: Risk of bias: no concerns; Inconsistency: no concerns; Indirectness: no concerns; Imprecision: the information provides from a small sample; Publication bias: no concerns.
Summary of findings (iSoF) Table
Efficacy and effectiveness of the vaccine in subgroups
Sex
Randomized trials
The proportion of females in the COVE trial was 43% (14372 out of 30346 participants) [El Sahly HM, 2021 ].
The relative risk of contracting COVID-19 in men in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.08 (95% CI 0.06 to 0.12). This means Moderna COVID-19 vaccine reduced the risk of contracting COVID-19 in men by 92%, compared with placebo vaccine.
The relative risk of contracting COVID-19 in women in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.07 (95% CI 0.04 to 0.1). This means Moderna COVID-19 vaccine reduced the risk of contracting COVID-19 in women by 93%, compared with placebo vaccine.
The magnitude of the effect was similar between the subgroups, and there was no statistical evidence of a subgroup effect by sex
Age
Randomized trials
The proportion of patients ≥65 years of age in the COVE trial was 25% (7512 out of 30351 participants) [El Sahly HM, 2021 ].
The relative risk of contracting COVID-19 (>65y) in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.11 (95% CI 0.05 to 0.21). This means Moderna COVID-19 vaccine reduced the risk of Contracting COVID-19 (>65y) by 89%, compared with placebo vaccine.
The relative risk of contracting COVID-19 (>75y) in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.03 (95% CI 0 to 0.46). This means Moderna COVID-19 vaccine reduced the risk of Contracting COVID-19 (>75y) by 97%, compared with placebo vaccine.
The phase 2, open-label study QHD00028 is currently evaluating the efficacy/safety of the vaccine in fully vaccinated adults with mRNA-1273 65 years of age and older [Sanofi Pasteur, a Sanofi Company, 2021 ].
The phase 4, randomized controlled trial mRNA-1273-D3-2021 is currently evaluating the efficacy/safety of the vaccine in vaccinated residents ≥65 years that received [Mark Loeb, 2021 ].
Other comparative studies
The phase 1 study 20-0003 [Anderson EJ, 2020 ], NCT04283461 number, was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). This study showed that binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients. A follow-up of this study at 119 days after the first vaccination [Widge AT, 2021 ] showed that despite a slight expected decline in titers of binding and neutralizing antibodies, the vaccine provided durable humoral immunity and elicited primarily CD4 type 1 helper T responses. There is no evidence that indicates a lower efficacy in older adults. It is important to notice that very few patients >80 years old were included.
Rane MS et al was a case control study conducted in the United States that included data from 931,972 patients with vaccine records: 39,185 with a positive test and 892,787 with a negative test. The study estimated Vaccine Effectiveness (VE) against symptomatic infection in a population of patients seeking care at CityMD, a large ambulatory care center in New York and neighboring areas. VE against symptomatic infection for BioNTech BNT162b and mRNA-1273 vaccines combined was 96% (95% CI, 95% to 97%) in the pre-Delta period and 79% (95% CI, 77% to 81%) in the Delta period. Adjusted VE against any infection was higher in all subgroups in the pre-Delta period compared with the Delta period. VE for participants aged 12 to 15 years old was 85% (95% CI, 81% to 88%) during the Delta period. VE was lower for adults aged 64 years or more compared with <64 years, even in the pre-Delta period. [Rane MS, 2022 ]
Children and adolescents
Randomized trials
The TeenCove or study P203 (NCT04649151) was a phase 2/3 trial sponsored by Moderna evaluating vaccine efficacy in adolescents from 12 to 17 years of age. Results of the study showed an efficacy of the vaccine of 95% after the second dose [Ali K, 2021 ].
The KidCOVE trial or study P204 (NCT04796896) is an ongoing phase 2/3 randomized trial sponsored by Moderna evaluating vaccine efficacy in children from 6 to 11 years of age. Preliminary results showed an efficacy of 88% after the second dose [Creech CB, 2022 ].
Other comparative studies
Levy M et al is a comparative study conducted in France. The study included pediatric patients diagnosed with multisystem inflammatory syndrome admitted to 1 of the 41 French pediatric intensive care units (PICUs) between September 1, 2021, and October 31, 2021. The Hazard ratio for multisystem inflammatory syndrome in children was 0.09 (95% CI, 0.04-0.211) after the first vaccine dose compared with unvaccinated adolescents. Sensitivity analyses showed similar results. The authors suggest that COVID-19 mRNA vaccination was associated with a lower incidence of multisystem inflammatory syndrome in adolescents [Levy M, 2021 ].
González S et al was a retrospective cohort study conducted in Argentina including 1,536,435 participants: 689,552 in the BIBP vaccine group and 846,883 in mRNA vaccine group (539,093 with Pfizer/Pfizer schedule, 15,552 with Pfizer/Moderna schedule and 44,862 with Moderna/Pfizer schedule. mRNA-1273 and BNT162b2 vaccines were administered to 12−17- year subjects; and BBIBP-CorV to 3−11-year subjects. Vaccine effectiveness for the mRNA vaccine group was 80.0% (95% CI 64.3 to 88.0) for the 12−17 age (mRNA vaccines) subgroup. [González S, 2022 ]
Castelli JM et al was a test-negative case-control study conducted in Argentina that included 844,460 children and adolescents without previous SARS-CoV-2 infection eligible to receive a primary vaccination schedule. The aim was to assess the effectiveness of different combinations of mRNA vaccines in children and adolescents. Vaccine effectiveness (VE) for the Pfizer/Moderna heterologous schedule was 88.9% (95% CI, 66.1% to 96.4%) during the Delta predominance period, and 40.6% (95% CI, 29.4 to 50.0) during the Omicron predominance period. VE for the Moderna primary schedule was 70.2% (95% CI, 66.8 to 73.1) during the Delta predominance period, and 17.9% (95% CI, 14.0 to 21.5) during the Omicron predominance period. [Castelli JM, 2022 ]
Rane MS et al was a case control study conducted in the United States that included data from 931,972 patients with vaccine records: 39,185 with a positive test and 892,787 with a negative test. The study estimated Vaccine Effectiveness (VE) against symptomatic infection in a population of patients seeking care at CityMD, a large ambulatory care center in New York and neighboring areas. VE against symptomatic infection for the BioNTech BNT162b and mRNA-1273 vaccines combined was 96% (95% CI, 95% to 97%) in pre-Delta period and 79% (95% CI, 77% to 81%) in Delta period. Adjusted VE against any infection was higher in all subgroups in the pre-Delta period compared with the Delta period. VE for participants aged 12 to 15 years old was 85% (95% CI, 81% to 88%) during the Delta period. VE was lower for adults aged 64 years and more compared with <64 years, even in the pre-Delta period. [Rane MS, 2022 ]
Fleming-Dutra et al was a comparative study conducted in United States that assessed monovalent mRNA vaccine effectiveness against symptomatic SARS-CoV-2 infection. This study analized data from the Increasing Community Access to Testing program, which provides SARS-CoV-2 testing to persons aged ≥3 years at pharmacy and community-based testing sites nationwide. Vaccine effectiveness (VE) of the second Moderna dose against symptomatic infection was 60% (95% CI, 49% to 68%). VE of monovalent Pfizer-BioNTech doses (complete primary series) against symptomatic infection was 31% (95% CI, 7% to 49%). [Fleming-Dutra KE, 2023 ]
Pregnancy
Randomized trials
The available data are insufficient to assess vaccine efficacy since no clinical trial has included this group.
Other comparative studies
Jorgensen et al was a case-control test-negative design conducted in Canada that included 8,809 infants whose mothers had been vaccinated during pregnancy with Pfizer or Moderna. Vaccine Effectiveness (VE) for the primary vaccine series was 95% (95% CI, 88% to 98%) against Delta infection and 45% (95% CI, 37% to 53%) against Omicron infection. VE for the primary plus booster vaccine series was 73% (95% CI, 61% to 80%) against Omicron infection [Jorgensen SCJ, 2023 ]
Breast-feeding
Randomized trials
The available data are insufficient to assess vaccine efficacy since no clinical trial has included this group.
Other comparative studies
Golan et al. was a prospective cohort study that enrolled 50 lactating women who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM increased significantly in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation [Golan Y et al., 2021 ].
Alisa Fox et al. was a cohort study that enrolled 50 lactating women (23 participants had received Pfizer vaccine, 14 had received Moderna vaccine, and 13 had received Janssen Vaccine). 50 pairs of milk samples were obtained from vaccine recipients within 1 week before vaccination and 14 days (Pfizer/Moderna) or 28 days (Janssen) after completion of the vaccine regimen. Results showed that Moderna milk samples exhibited significantly greater relative IgA than Pfizer and Janssen recipients. It was found that 100% and 87% of Moderna and Pfizer recipient post-vaccine milk samples contained positive levels of Spike-specific IgG [ ].
Immunocompromised persons
Randomized trials
The proportion of participants with HIV in the COVE trial was 0.6% (179 out of 30351 participants) [Baden LR, 2021 ].
In a post hoc analysis, the relative risk of contracting COVID-19 in participants living with HIV that received Moderna COVID-19 vaccine versus those that received placebo vaccine was 0.32 (95% CI 0.01 to 7.67) [FDA, 2020 ].
COVERALL was a phase 3 randomized trial conducted in Switzerland. The study enrolled 430 patients (412 included in the intention to treat analysis): 341 patients living with HIV and 71 solid organ transplant recipients. Patients were randomized to Moderna or Pfizer–BioNTech. The primary endpoint was antibody response to the SARS-CoV-2 spike (S1) protein receptor binding domain 8 weeks after the second vaccination. The percentage of patients showing an immune response to Moderna was 92.1% (95% CI 88.4 to 95.8) and 94.3% (95% CI 91.2 to 97.4) for Pfizer–BioNTech fulfilling the non-inferiority of Moderna. With the ABCORA 2 test, 89.1% (95% CI 84.8 to 93.4) had an immune response to mRNA-1273 and 89.5% (95% CI 85.4 to 93.7) to BNT162b2. Based on the Elecsys test, all patients living with HIV had an antibody response while for solid organ transplant recipients only 60.6% (95% CI 49.2 to 71.9%) had titres above the cut-off [Speich B, 2022 ].
The Hall VG et al was a phase 4, randomized, placebo-controlled trial evaluating vaccine efficacy in organ-transplant recipients. Results showed that at month 4 post-vaccination, an anti-RBD antibody level of at least 100 U per milliliter was present in 33 of 60 patients (55%) in the mRNA-1273 group and in 10 of 57 patients (18%) in the placebo group (relative risk, 3.1; 95% CI: 1.7 to 5.8; P<0.001) [Hall VG, 2021 ].
Heinzel et al was a secondary analysis of the phase 2 randomized trial BOOST-TX conducted in Austria. The study enrolled 201 kidney transplant recipients without detectable SARS-CoV-2 specific antibodies following two doses of an mRNA vaccine. Participants were randomized to a third dose of the same mRNA vaccine (the mRNA group) or a dose of the vector vaccine (Janssen, Ad26COVS1). A total of 169 patients were available for the 3-month follow-up. Overall, seroconversion at 3 months was similar between both groups (45% vs. 50% for mRNA and the vector group, respectively; p = 0.539). However, when applying higher cut-off levels, a significantly larger number of individuals in the vector group reached antibody levels > 141 and > 264 BAU/ml at the 3-month follow-up (141 BAU/ml: 4% vs. 15%, p = 0.009 and 264 BAU/ml: 1% vs. 10%, p = 0.018 for mRNA vs. the vector vaccine group, respectively). [Heinzel A, 2022 ]
RECOVAC was a randomized trial conducted in the Netherlands that enrolled 333 kidney transplant recipients (KTR) who did not seroconvert after an initial mRNA vaccine schedule: 230 KTRs were randomly assigned in a 1:1:1 manner to receive 100 μg mRNA-1273, 2 × 100 μg mRNA-1273, or Ad26.COV2-S vaccination. In addition, 103 KTRs receiving 100 μg mRNA-1273, were randomly assigned 1:1 to continue (mycophenolate mofetil+) or discontinue (mycophenolate mofetil-) mycophenolate mofetil or mycophenolic acid treatment for 2 weeks. The primary outcome was the percentage of participants with a spike protein (S1)-specific IgG concentration of at least 10 binding antibody units per mL at 28 days after vaccination. The seroreponse rates were 68% (95% CI, 56% to 79%) for the 2 × mRNA-1273 group, 63% (95% CI, 51% to 74%) for the Ad26.COV2-S group and 68% (95% CI, 57% to 79%) for the single mRNA-1273 group. The seroresponse rate in mycophenolate mofetil- was 80% (95% CI, 66% to 91%) and 67% (95% CI, 52% to 80%) in mycophenolate mofetil+. [Kho MML, 2022 ]
Bonelli et al was a randomized controlled trial in Austria that assigned 60 patients under rituximab treatment who did not seroconvert after their primary mRNA vaccination with either BNT162b2 or mRNA-1273, to receive a third dose, either using the same mRNA (28/30) or the vector vaccine ChAdOx1 nCoV-19 (27/30). Seroconversion rates at week 4 were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccines (p=0.6). Overall, 27% of patients seroconverted; specific T cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. 3/37 (8%) of patients without and 12/18 (67%) of the patients with detectable peripheral B cells seroconverted. No serious adverse events related to immunization were observed. [Bonelli M, 2022 ]
Other comparative studies
Schiavetti et al. is a retrospective study conducted in Italy which analyzed data from Multiple Sclerosis centers on patients with Multiple Sclerosis undergoing the SARS-CoV-2 vaccination [Irene Schiavetti, 2022 ]. This study estimated the rate of breakthrough infections and of infections requiring hospitalization per disease-modifying therapy. The rate of breakthrough infections was significantly higher in patients treated with ocrelizumab (RR=3.55, 95% CI: 2.74-4.58) and fingolimod (RR=2.65, 95% CI: 1.75-4.00) compared to patients treated with all the other disease-modifying therapies. In the ocrelizumab group, the hospitalization rate was 16.7% vs 19.4% in pre-vaccination rates and it was 3.9% in all the other disease-modifying therapy groups vs 11.9% in pre-vaccination rates. The authors suggest that the risk of breakthrough SARS-CoV-2 infections is higher in patients treated with ocrelizumab and fingolimod, and the rate of severe infections was significantly reduced in all the disease-modifying therapies excluding ocrelizumab [Irene Schiavetti, 2022 ].
Huang HJ et al. included 241 transplant candidates and 1,163 transplant recipients (Pfizer=858; Moderna=546). Data were collected 2 weeks to 3 months after the second dose. The study showed that transplant candidates exhibited a response to the anti-SARS-CoV-2 Total Ig of 93.5% after two doses. Anti-spike ELISA assay demonstrated that 91.9% of transplant candidates increased in titer from <1:50 (negative) to ≥1:50 (positive) after two doses. For transplant recipients, 30.7% exhibited a response (anti-SARS-CoV-2 IgG assay)after the second dose. Results for the anti-spike titer in recipients became positive in 30.1% after two doses [Huang HJ, 2022 ].
Tenforde MW et al. included 2,952 adults (1,385 COVID-19 case-patients and 1,567 COVID-19–negative controls) hospitalized at 21 hospitals between August - December 2021. Among them, 1,077 adults with immunocompromising conditions (twos-dose of Pfizer= 332; two-dose Moderna=238; three dose Pfizer =120, Three-dose Moderna= 57, Both vaccines= 4). The study showed results combined for Pfizer and Moderna COVID-19 vaccine. Among patients with immunocompromising conditions, those who received 2-dose were more likely to be enrolled as a case-patient (34%) than those received 3-dose (20%). Vaccine Effectiveness against COVID-19 hospitalization among adults without immunocompromising conditions was 82% (95% CI 77% to 86%) for 2 doses and 97% (95% CI 95% to 99%) for 3 doses . Vaccine effectiveness against COVID-19 hospitalization among adults with immunocompromising conditions was 69% (95% CI 57% to 78%) for 2 doses and 88% (95% CI 81% to 93%) for 3 doses [Tenforde MW, 2022 ].
Li LL et al. was a comparative cohort study conducted in United States [Li LL, 2022 ], evaluating impact of prior SARS-CoV-2 infection on incidence of hospitalization and adverse events after receiving Pfizer, Moderna or Janssen COVID-19 vaccines.
Aharon D et al. was a comparative cohort study conducted in United States [Aharon D, 2022 ], evaluating whether Pfizer or Moderna COVID-19 vaccine is associated with controlled ovarian hyperstimulation or early pregnancy outcomes in patients who undergo in vitro fertilization.
Lombardi A et al. was a cohort study conducted in Italy. The study enrolled 71 participants living with HIV, mostly male (84·5%), with a mean age of 47 years, a median CD4+ T cell count of 747·0 cells per µL and a median HIV viral load <50 copies/mL. The study results showed that inoculation with mRNA-1273 vaccine given 4 weeks apart produced detectable humoral immune response, similar to individuals without HIV infection [Lombardi A, 2021 ].
Lin et al conducted a sub-analysis of a previous study [Sheng WH, 2022 ] wich compare the immunogenicity of heterologous ChAdOx1/mRNA-1273 versus standar homologous ChAdOx1 and mRNA-1273m vaccination. 399 participants were enrolled, there were 100, 100, 100, and 99 participants undergoing ChAdOx1/ChAdOx1 8 weeks apart (Group 1), ChAdOx1/mRNA-1273 8 weeks apart (Group 2), ChAdOx1/mRNA-1273 4 weeks apart (Group 3), and mRNA-1273/mRNA-1273 4 weeks apart (Group 4), respectively. The majority of the enrolled participants were ≤50 years with 74.7% being women. Among participants undergoing boost vaccination with mRNA-1273, compared with healthy participants aged ≤50 years, participants with immunocompromising conditions had similar anti-SARS-CoV-2 spike IgG titers 4 weeks after booster vaccination (geometric means, 1769.66 vs. 1946.41 BAU/mL; P = 0.255). Only participants with autoimmune diseases and receiving hydroxychloroquine, low-dose steroid, methotrexate, and/or sulfasalazine had numerically lower anti-SARS-CoV-2 spike IgG titers 4 weeks after booster vaccination compared to those without (geometric means, 1474.34 vs. 1923.23 and 1590.61 vs. 1918.38 BAU/mL; both P > 0.05). While anti-SARS-CoV-2 spike IgG titers 4 weeks after booster vaccination were comparable between participants receiving and not receiving NSAIDs (geometric means, 1894.94 vs. 1903.09 BAU/mL, P = 0.981), those receiving COX-2 selective NSAIDs had numerically lower titers (geometric means, 1362.55 vs. 1915.86 BAU/mL, P = 0.179). [Lin KY, 2022 ]
Coburn SB et al was a cohort study conducted in United States. The study included 113,994 patients (33,029 people with HIV and 80,965 people without HIV). The aim of the study was to determine whether HIV status was associated with increased rate or risk of COVID-19 breakthrough infection among fully vaccinated patients in the United States by vaccination type and, among PWH, by immune and viral suppression status. The incidence rate of breakthrough infections was higher in people with HIV (55 [95% CI, 52-58] cases per 1000 person-years) vs people without HIV (43 [95% CI, 42-45] cases per 1000 person-years). The breakthrough rate was highest with the Janssen vaccine (70 [95% CI, 63-78] cases per 1000 person-years), followed by Pfizer (54 [95% CI, 52-56] cases per 1000 person-years), and Moderna (34 [95% CI, 32-36] cases per 1000 person-years) [Coburn SB, 2022 ]
Risk M et al was a retrospective cohort study conducted in the United States including 168,414 participants: 133,238 vaccinated with mRNA vaccines and 35,176 unvaccinated. Based on data from the Michigan Medicine health-care system, the Michigan State Registry and chart-reviewed COVID-19 hospitalization data. Including patients 18 years old and above, who received mRNA based COVID-19 vaccines. During the Omicron dominant period December 2021 to March 2022. The effectiveness of the Moderna vaccine during the Omicron period in immunocompromised participants the effectiveness was 57% (95%CI 29 to 74) for two doses and 60% (95%CI 42 to 73) for three doses. [Risk M, 2022 ]
Embi P et al. conducted a case-control study with a test-negative design among eight VISION Network sites in the United States during the Delta variant predominance period. Persons aged 18 years and older with ≥1 immunocompromising conditions were included and compared with non-immunocompromised individuals. It included 8,848 emergency department/urgent care (ED/UC) events and 18,843 hospitalizations among immunocompromised (IC) patients; and 200,071 ED/UC events and 70,882 hospitalizations among non-IC patients. In the IC population, adjusted vaccine effectiveness (VE) for the Moderna vaccine was 69% (95% CI, 62% to 76%) for ED/UC events, and 76% (95% CI, 72% to 80%) for hospitalization, measured 14 days after the second dose. After a third dose, VE was 77% (95% CI, 58% to 87%), and 87% (95% CI, 79% to 92%) for ED/UC events and hospitalization, respectively. Preprint. [Peter J. Embi, 2022 ]
Wagner A et al was an open-label phase 4 randomized trial conducted in Austria, including 263 patients: 63 with solid tumors, 70 with multiple myeloma, 130 with inflammatory bowel disease and 66 controls. The seronegativity rate 6 months after the primary schedule was 8% in the solid tumors group and 21,1% in the multiple myeloma group. [Furer V, 2022 ]
Smith JB was a retrospective cohort study conducted in United States that included 3,974 patients with Multiple Sclerosis. The aim was to examine whether rituximab treatment is associated with an increased risk of hospitalization for COVID-19 among SARS-CoV-2–vaccinated persons with multiple sclerosis. During the study period, 437 patients (22.4%) receiving rituximab were unvaccinated. These patients were at significantly higher risk of COVID-19 hospitalizations compared with vaccinated individuals with an adjusted odds ratio of 4.07 (95% CI, 2.29-7.24). [Smith JB, 2022 ]
Persons with recent COVID-19
Most guidelines recommend that individuals who have had COVID-19 should receive an identical vaccine regimen as those who have not had the infection.
Randomized trials
Participants with a known history of COVID-19 were excluded from the COVE trial [Baden LR, 2021 ],[FDA, 2020 ] and there was only one case of COVID-19 among study participants with positive SARS-COV-2 infection status at baseline. Thus, this trial does not offer information to assess the benefit in individuals with recent infection.
Other comparative studies
Saadat S et al [Saman Saadat, 2021 ] assessed 59 health care workers with and without history of SARS-CoV-2 infection prior to vaccine. After a single dose of the SARS-CoV-2 vaccine (30/59 vaccinated with Moderna vaccine and the other half received Pfizer vaccine), individuals that had prior SARS-CoV-2 infection had higher titers of binding and functional antibodies than individuals that had no history of infection.
Vaccine effectiveness (other comparative studies)
Contracting COVID-19
Chung H et al. was a nested case-control study conducted in Canada. The study enrolled 324,033 participants that received Moderna or Pfizer COVID-19 vaccine. The effectiveness of the vaccine in symptomatic infections, observed 14 days after the first dose, was 60%, and increases to 75% between 35-71 days. The effectiveness at 7 days of the second dose was 91%. The effectiveness of the vaccine against hospitalization or death was 70% with the first dose and 91% with the second dose. In adults ≥70 years, the effectiveness was comparable to that in younger people for all intervals after 28 days. [Chung H, 2021 ]
Flacco M et al. conducted a retrospective cohort study conducted in Italy. The study enrolled 245,226 participants: 69,539 Vaccine; 175,687 Control. Based on data from an interim analysis of COVID-19 vaccines effectiveness in the entire population of an Italian Province between 2 January to 21 May 2021. Results showed vaccine effectiveness of 99 to 100% (n = 0 infections)[Flacco ME, 2021 ].
Pawlowski C et al. was a retrospective cohort study conducted in the United States. The study enrolled 136,532 participants: 68,266 vaccine (16,471 Moderna COVID-19 vaccine); 68,266 Control. Based on data from the Mayo Clinic health system between December 1 2020 and April 20, 2021. Results showed vaccine effectiveness of 92.3% (95% CI 82.4% to 9.3%) and infection rate 0.014%/ 0.19% (vaccinated/unvaccinated) [Pawlowski C, 2021 ].
Amanda Zheutlin et al. was a case-control study conducted in the United States. The study included data from 168,857,729 participants with 7,368,289 receiving the Moderna vaccine. Based on claims and laboratory data from vaccinated individuals between January 1 and September 7, 2021. Odds ratios (OR) for developing incident breakthrough infection, hospitalization or ICU admission in months two through six following full vaccination were estimated relative to the first month after full vaccination. The study results showed evidence of waning protection against infections starting in month 2 from vaccination for both BNT162b2 and mRNA-1273 and in month 4 for Ad26.COV2.S. Evidence of waning protection against hospitalization started in month 2 for BNT162b2 and in month 3 for mRNA-1273. There was no evidence of waning protection against hospitalization for Ad26.COV2.S. No waning of protection was observed at any time for ICU admissions for all three vaccines [Amanda Zheutlin, 2022 ].
Molani S et al. was a comparative cohort study conducted in the United States. The study included 7,620,084 records: 2,627,914 vaccine-induced immunity cohorts (Pfizer-BioNTech, Moderna or Janssen) and 191,722 infection-induced immunity cohorts. The study was based on data from Providence-St. Joseph Health electronic health records. The vaccine-induced cohort period data were collected from December 12, 2020, and the infection-induced cohort data were collected from the beginning of the pandemic. Data collection ended on May 11, 2021. Survival against breakthrough infection for Moderna was 99,7% in 180 days [Sevda Molani, 2022 ].
Chadeau-Hyam M et al. was a cohort study conducted in the United Kingdom. The study enrolled 172,862 participants: 76,291 vaccine group; 96,571 control group. Based on data from a series of random cross-sectional surveys in the general population of England aged 5 years and older, between May 2020 and September 2021, the study results showed vaccine effectiveness of 75.1% (95%CI 22.7 to 92.0) against infection in vaccinated individuals [Chadeau-Hyam M, 2022 ].
Draws PE et al. was a case-control study conducted in the United States. The study enrolled 4,547,945 participantes: 1,732,112 were fully vaccinated with Pfizer–BioNTech and 1,066,645 were fully vaccinated with Moderna. A Pfizer–BioNTech booster was administered to 609,153 individuals and a Moderna booster was administered to 395,634 individuals The study is based on statewide COVID-19 vaccination data from the Minnesota Immunization Information Connection (MIIC) linked via a privacy-preserving record linkage process with distributed electronic health record (EHR) data from the 11 largest health systems in Minnesota. The main results showed that vaccine effectiveness after 26 weeks from the second dose was 65% (95% CI 65 to 66) for the Moderna COVID-19 Vaccine. [Drawz PE, 2022 ]
Roberts E et al. was a case-control study conducted in the United States. The study analyzed data from 170,487 positive COVID-19 adult patients: 74,060 fully vaccinated, 18,425 partially vaccinated and 7,187 fully vaccinated, and received at least 1 booster dose. The aim was to investigate the COVID-19 vaccine effectiveness against test positivity and severe COVID-19 outcomes across 2021 and to examine vaccine effectiveness stratified by the two most common vaccines Pfizer-BioNTech and Moderna, and by sociodemographic and clinical characteristics that are associated with COVID-19 outcomes. Results reported vaccine effectiveness for contracting COVID-19 of 88.1% (95% CI 85.5 to 90.2). [Emily Roberts, 2022 ].
Winkelman TNA et al was a comparative cohort study conducted in the USA. The study included 4,431,190 individuals: 3,013,704 fully vaccinated and 1,417,486 not vaccinated. It used data from the Minnesota Immunization Information Connection from October 25, 2020, through October 30, 2021, that were linked with electronic health record (EHR) data from health systems collaborating as part of the Minnesota EHR Consortium (MNEHRC). Vaccine Effectiveness for Medically Attended SARS-CoV-2 Infections was 66% (95% CI 65 to 67) and 69% (95% CI 67 to 71) for adults ≥ 65 years [Winkelman TNA, 2022 ].
Oren Miron et al was a secondary analysis of a phase 3 randomized clinical trial conduct in United States. The study reunited data from 30,420 participants aged 18 to 95 years that were enrolled to receive two doses of Pfizer-BioNTech vaccine on days 0 and 28 (n= 15,181) or were enrolled to the placebo group (n= 15,170). Vaccine effectiveness (VE) was defined by the ratio between the COVID-19 cumulative rate in vaccinated participants and in the placebo group participants. The study results showed that the cumulative incidence at day 111 of COVID-19 increased by 0.19% in the intervention group and 2.84% in the placebo group.The mRNA-1273 effectiveness at days 7, 14, and 21 was 33%, 62% and 90% respectively, followed by a mean of 95% effectiveness until day 112 [Oren Miron, 2021 ].
Lin DY et al, was a comparative cohort study conducted in the USA. The study included 10,600,823 individuals, among which were 2,771,364 cases of COVID-19. Based on data from the North Carolina COVID-19 Surveillance System and the Covid-19 Vaccine Management System, including data from residents of North Carolina from December 11, 2020, to September 8, 2021. Vaccine effectiveness of 2 doses of Moderna against infection was 76.5% (95% CI 75.7 to 77.2) and 48.4% (95% CI 47.5 to 49.3), 1 and 10 months after vaccination respectively. [Lin DY, 2022 ]
Chung et al. conducted a case-control study with a test-negative design to estimate vaccine effectiveness (VE) against SARS-CoV-2 infection after the primary schedule of any combination of BNT162b2, mRNA-1273, and ChAdOx1, between January 11th and November 21st 2021 in Ontario, Canada. They included 261,360 test-positive cases (of any SARS-CoV-2 lineage) and 2,783,699 individuals as test-negative controls. VE for a homologous mRNA-1273 schedule 7 to 59 days after the second dose was 92% (95% CI, 91% to 92%) against any infection and 95% (95% CI, 94% to 96%) against symptomatic infection. VE >240 days after the second dose was 80% (95% CI, 71% to 86%) against any infection and 87% (95% CI, 78% to 92%) against symptomatic infection. [Chung H, 2022 ]
Rane MS et al was a case control study conducted in the United States that included data from 931,972 patients with vaccine records: 39,185 with a positive test and 892,787 with a negative test. The study estimated Vaccine Effectiveness (VE) against symptomatic infection in a population of patients seeking care at CityMD, a large ambulatory care center in New York and neighboring areas. VE against symptomatic infection for the BioNTech BNT162b and mRNA-1273 vaccines combined was 96% (95% CI, 95% to 97%) in pre-Delta period and 79% (95% CI, 77% to 81%) in the Delta period. Adjusted VE against any infection was higher in all subgroups in the pre-Delta period compared with the Delta period. VE for participants aged 12 to 15 years was 85% (95% CI, 81% to 88%) during the Delta period. VE was lower for adults aged 64 years and older compared with <64 years, even in the pre-Delta period. [Rane MS, 2022 ]
Weng C et al was a comparative study conducted in United States that included 38,602 participants: 22,247 with at least one SARS-CoV-2 PCR test. The aim was to assess mRNA vaccine effectiveness (VE) in preventing SARS-CoV-2 infections. Adjusted VE of 2 doses of Moderna was 97.5% (95% CI, 82.5% to 99.7%). Adjusted VE against Omicron (2 doses of Moderna) was 25.6% (95% CI, 10.7% to 39.0%). Adjusted VE against Omicron (3 doses of Moderna) was 71.2% (95% CI, 24.0% to 90.8%). [Weng CH, 2023 ]
Puranik A et al was a case control study conducted in United States that included data from 15,313 participants: 2,364 cases and 12,949 controls. The aim was to assess the durability of protection against symptomatic infection after vaccination with the Moderna vaccine. Odds of symptomatic infection at 250 days after full vaccination compared to the date of full vaccination was 2.24 (95% CI, 1.19-5.13). [Puranik A, 2022 ]
Bello-Chavolla OY et al was retrospective cohort study conducted in Mexico, including 793,487 vaccinated and 4,792,388 unvaccinated individuals. This study estimated vaccine effectiveness (VE) against infection and hospitalization, based on data from the COVID-19 surveillance system between December 2020 and September 2021. Among 3,764 participants vaccinated with Moderna, VE against infection was 91.45% (95% CI, 90.34% to 92.43%), and VE against hospitalization was 78% (95% CI, 69% to 84.38%). [Bello-Chavolla OY, 2023 ]
Shioda K et al was a trial emulation study conducted in the United States that included 6,128,364 participants: 2,337,570 with the Moderna vaccine and 3,790,794 with the Pfizer vaccine. The aim was to assess the effectiveness of mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) against SARS-CoV-2 infection. Weighted risk of infection was RR 0.79 (95% CI, 0.78-0.81) for the Pfizer vaccine and RR 0.90 (95% CI, 0.87-0.92) for the Moderna vaccine. [Kayoko Shioda, 2023 ]
Contracting severe COVID-19
Pawlowski C et al. was a retrospective cohort study conducted in the United States. The study enrolled 136,532 participants: 68,266 vaccine (16 471 Moderna COVID-19 vaccine); 68,266 Control. Based on data from the Mayo Clinic health system between December 1,2020 and April 20, 2021. Results showed vaccine effectiveness 90.6% (95% CI 76.5% to 97.1%) infection rate 0.006%/0.064% (vaccinated/unvaccinated) [Pawlowski C, 2021 ].
Amanda Zheutlin et al. was a case-control study conducted in the United States. The study included data from 168,857,729 participants with 7,368,289 receiving the Moderna vaccine. Based on claims and laboratory data from vaccinated individuals between January 1 and September 7, 2021. Odds ratios (OR) for developing an incident breakthrough infection, hospitalization, or ICU admission in months two through six following full vaccination were estimated relative to the first month after full vaccination. The study results showed evidence of waning protection against infections starting in month 2 from vaccination for both BNT162b2 and mRNA-1273 and in month 4 for Ad26.COV2.S. Evidence of waning protection against hospitalization started in month 2 for BNT162b2 and in month 3 for mRNA-1273. There was no evidence of waning protection against hospitalization for Ad26.COV2.S. No waning of protection was observed at any time for ICU admissions for all three vaccines [Amanda Zheutlin, 2022 ].
Lytras T et al. included a total of 14,676,605 vaccine administered doses (Pfizer= 11,427,784; Moderna=1,161,905; AstraZeneca=1,505,334; Janssen= 581,582). Data were collected between 11 January 2020 and 8 December 2021. The study showed that two doses of Pfizer, Moderna, or AstraZeneca COVID-19 vaccines offered vaccine effectiveness >90% against both intubation and death across all age groups. The effectiveness of the Janssen COVID-19 vaccine ranged between 61-81%. There was some waning over time, but vaccine effectiveness remained >80% at six months, and three doses increased vaccine effectiveness again to near 100%. Vaccination prevented an estimated 19,691 COVID-19 deaths (95% CI 18,890 to 20,788) over the study period [Theodore Lytras, 2022 ].
Draws PE et al. was a case-control study conducted in the United States. The study enrolled 4,547,945 participantes: 1,732,112 were fully vaccinated with Pfizer–BioNTech and 1,066,645 were fully vaccinated with Moderna. A Pfizer–BioNTech booster was administered to 609,153 individuals and a Moderna booster was administered to 395,634 individuals The study is based on statewide COVID-19 vaccination data from the Minnesota Immunization Information Connection (MIIC) linked via a privacy-preserving record linkage process with distributed electronic health record (EHR) data from the 11 largest health systems in Minnesota. The main results showed that vaccine effectiveness after 26 weeks from the second dose was 65% (95% CI 65 to 66) for the Moderna COVID-19 Vaccine. [Drawz PE, 2022 ]
Roberts E et al. was a case-control study conducted in the United States. The study analyzed data from 170,487 positive COVID-19 adult patients: 74,060 fully vaccinated, 18,425 partially vaccinated and 7,187 fully vaccinated, and received at least 1 booster dose. The aim was to investigate the COVID-19 vaccine effectiveness against test positivity and severe COVID-19 outcomes across 2021 and to examine vaccine effectiveness stratified by the two most common vaccines Pfizer-BioNTech and Moderna, and by sociodemographic and clinical characteristics that are associated with COVID-19 outcomes. Results reported vaccine effectiveness for contracting COVID-19 of 88.1% (95% CI 85.5 to 90.2). [Emily Roberts, 2022 ].
Winkelman TNA et al was a comparative cohort study conducted in the USA. The study included 4,431,190 individuals: 3,013,704 fully vaccinated and 1,417,486 not vaccinated. It used data from the Minnesota Immunization Information Connection from October 25, 2020, through October 30, 2021, that were linked with electronic health record (EHR) data from health systems collaborating as part of the Minnesota EHR Consortium (MNEHRC). Vaccine Effectiveness for SARS-CoV-2–Related Hospitalizations: was 81% (95% CI 79 to 82) and 69% (95% CI 65 to 72) [Winkelman TNA, 2022 ].
Lin DY et al, was a comparative cohort study conducted in the USA. The study included 10,600,823 individuals, among which were 2,771,364 cases of COVID-19. IBased on data from the North Carolina COVID-19 Surveillance System and the Covid-19 Vaccine Management System, including data from residents of North Carolina from December 11, 2020, to September 8, 2021. Vaccine effectiveness of 2 doses of Moderna against hospitalization was 77.2% (95% CI 63.8 to 72.2) and 72.7% (95% CI 67.8 to 77), 1 and 10 months after vaccination respectively. [Lin DY, 2022 ]
Grasselli G et al was a cohort study conducted in Italy that included 10,107,674 residents, among which 7,863,417 were vaccinated. The study was based on data from the Italian National Health Service, from August 2021 to August 2022. The study included participants vaccinated with Pfizer, Moderna, AstraZeneca and Janssen. The effectiveness of mRNA vaccines against ICU Admission was IRR 0.10 (95 CI%, 0.08-0.12). IRR = Incidence Rate Ratio. [Lin DY, 2022 ]
Chung et al. conducted a case-control study with a test-negative design to estimate vaccine effectiveness (VE) against SARS-CoV-2 infection after the primary schedule of any combination of BNT162b2, mRNA-1273, and ChAdOx1, between January 11th and November 21st 2021 in Ontario, Canada. They included 261,360 test-positive cases (of any SARS-CoV-2 lineage) and 2,783,699 individuals as test-negative controls. VE for a homologous mRNA-1273 schedule 7 to 59 days after the second dose was 96% (95% CI, 95% to 97%) against severe outcomes (hospitalization or death) and 98% (95% CI, 88% to 100%), >240 days after the second dose. [Chung H, 2022 ]
Yuanyuan F et al. conducted an observational study to analyze vaccination status and SARS-CoV-2 infection data from more than 10.4 million participants in the national COVID Cohort Collaborative during an 18-month-period (December 2020 to June 2022) in the United States. Vaccine Effectiveness against COVID-19-related death was 46.22% (95% CI, 44.47% to 47.93%) for a Moderna primary schedule. [Yuanyuan Fu, 2022 ]
Anzalone AJ et al was a retrospective cohort study conducted in the United States that included 2,290,674 participants: 566,128 participants with 2 doses of mRNA vaccine and 1,724,546 non vaccinated participants. The aim was to explore associations between community factors and breakthrough infections. Adjusted odds ratio of hospitalization within 30 days of testing positive for SARS-CoV-2 was 0.58 (95% CI, 0.55-0.62) corresponding to a vaccine effectiveness against hospitalization of 42% (95% CI, 38% to 45%). [Anzalone AJ, 2023 ]
Bello-Chavolla OY et al was a retrospective cohort study conducted in Mexico, including 793,487 vaccinated and 4,792,388 unvaccinated individuals. This study estimated vaccine effectiveness (VE) against infection and hospitalization, based on data from the COVID-19 surveillance system between December 2020 and September 2021. Among 3,764 participants vaccinated with Moderna, VE against infection was 91.45% (95% CI, 90.34% to 92.43%), and VE against hospitalization was 78% (95% CI, 69% to 84.38%). [Bello-Chavolla OY, 2023 ]
Bouillon K et al was a comparative cohort study conducted in France that included data from 28,611,967 vaccinated participants: 7,161,658 with the Pfizer vaccine, 856,599 with the Moderna vaccine and 3,238,575 with the AstraZeneca vaccine. The aim was to estimate the effectiveness of two doses of Pfizer, Moderna and AstraZeneca vaccines. Vaccine effectiveness against hospitalization was 91% (95% CI, 91% to 92%), 95% (95% CI, 93% to 96%) and 91% (95% CI, 89% to 94%) for the Pfizer, Moderna, and AstraZeneca vaccines, respectively. [Bouillon K, 2022 ]
de Arriba Fernández et al was a retrospective cohort study conducted in Spain that included data from 110,726 vaccinated participants: 50,639 with the Pfizer vaccine, 27,914 with the Moderna vaccine, 7,551 with the Janssen vaccine and 8,065 with the AstraZeneca vaccine. The aim was to assess the risk of developing persistent COVID-19 or SARS-CoV-2 virus reinfection. Risk of reinfection or persistent COVID-19 was OR 0.09 (95% CI, 0.07-0.12), OR 0.09 (95% CI, 0.06-0.13), OR 0.15 (95% CI, 0.09-0.25) and OR 0.08 (95% CI, 0.04-0.16) for the Pfizer, Moderna, Janssen and AstraZeneca vaccines, respectively. [de Arriba Fernández A, 2023 ]
Transmission
Abu-Raddad LJ et al. was a retrospective cohort study conducted in Qatar. The study enrolled 384,246 participants: 192,123 received Moderna vaccine; 192,123 received Pfizer vaccine. Based on data from national Covid-19 electronic health databases of the two matched cohorts of participants between December 21, 2020, and October 20, 2021, and measuring the outcome 1 to 6 months after the second dose, the study results showed that vaccination with COVID-19 vaccines was associated with a lower incidence of SARS-CoV-2 breakthrough infection, with an adjusted Hazard Ratio (HR) for breakthrough infection of 0.82 (95%CI 0.60 to 1.12)[Abu-Raddad LJ, 2022 ].
Efficacy and effectiveness against SARS-CoV-2 variants
Immunogenicity outcomes
Alpha (B.1.1.7)
Lafon et al. used data from samples of 116 patients who had been vaccinated with AstraZeneca, Pfizer, or Moderna COVID-19 vaccines or had recovered from COVID-19. The study found that all the vaccines induced a neutralizing response against the Alpha variant that was higher than the wild-type virus. The mRNA vaccines generated an 82% increase in neutralizing activity, while the AstraZeneca vaccine induced a 13% increase. Responses against the Beta and Delta variants were lower for all vaccines than for wild-type viruses. Neutralizing activity against the Beta variant was 42 and 47% lower in AstraZeneca and Pfizer recipients while only 25% lower for Moderna recipients. The AstraZeneca vaccine had an 82% reduction in neutralizing activity against the Delta variant, and the Pfizer and Moderna vaccines had a decrease of 2% and 14% respectively [Lafon E, 2022 ].
Chuang et al. was a randomized controlled study made in Taiwan. It included data from samples of 340 health care workers (HCW) with prior Oxford-AstraZeneca homologous vaccination and that received one of the four vaccines as booster doses: Pfizer–BioNTech, half-dose Moderna, full dose Moderna or MVC-COV1901.The primary outcomes were humoral and cellular immunogenicity and the secondary outcomes safety and reactogenicity 28 days post-booster. The study found that the neutralizing activity increased significantly post boost (P < 0.0001) and the fold-rise ranged from 23.0 in MCV-COV1901 to 118.1 in mRNA1273 against the Alpha variant. After each booster vaccine, the neutralization titers against the Alpha variant were compatible with those of the wild type [Chih-Hsien Chuang, 2022 ].
ARNCOMBI was a randomized controlled trial conducted in France. The study included 414 individuals who received an mRNA vaccine first dose and a second dose of Pfizer-BioNTech or Moderna after 28 days. Measurement of neutralizing antibodies against the specific variants (Alpha, Beta, Delta) was performed on a representative population of 30 subjects randomly selected after stratification on vaccine schedule group, age (<40 years, ≥40 years, and <55 years, ≥55 years), and level of anti-spike IgG against the wild-type viral strains at D28 (<1000 BAU/mL, ≥1000 BAU/mL, and <5000 BAU/ml, ≥ 5000 BAU/mL). The study showed that the neutralizing antibodies titers against SARS-CoV-2 variants were not different between the homologous and heterologous vaccine groups [Janssen C, 2022 ].
Beta (B.1.351)
Lafon et al. used data from samples of 116 patients who had been vaccinated with AstraZeneca, Pfizer, or Moderna COVID-19 vaccines or had recovered from COVID-19. The study found that all the vaccines induced a neutralizing response against the Alpha variant that was higher than the wild-type virus. The mRNA vaccines generated an 82% increase in neutralizing activity, while the AstraZeneca vaccine induced a 13% increase. Responses against the Beta and Delta variants were lower for all vaccines than for wild-type viruses. Neutralizing activity against the Beta variant was 42 and 47% lower in AstraZeneca and Pfizer recipients while only 25% lower for Moderna recipients. The AstraZeneca vaccine had an 82% reduction in neutralizing activity against the Delta variant, and the Pfizer and Moderna vaccines had a decrease of 2% and 14% respectively [Lafon E, 2022 ].
ARNCOMBI was a randomized controlled trial conducted in France. The study included 414 individuals who received an mRNA vaccine first dose and a second dose of Pfizer-BioNTech or Moderna after 28 days. Measurement of neutralizing antibodies against the specific variants (Alpha, Beta, Delta) was performed on a representative population of 30 subjects randomly selected after stratification on vaccine schedule group, age (<40 years, ≥40 years, and <55 years, ≥55 years), and level of anti-spike IgG against the wild-type viral strains at D28 (<1000 BAU/mL, ≥1000 BAU/mL, and <5000 BAU/ml, ≥ 5000 BAU/mL). The study showed that the neutralizing antibodies titers against SARS-CoV-2 variants were not different between the homologous and heterologous vaccine groups [Janssen C, 2022 ].
Anderson et al. was a phase 2 randomized controlled trial conducted in the United States that included 96 participants with a primary schedule of Moderna: 48 with Monovalent prototype boost (100 mcg) of mRNA-1273, 25 with Monovalent variant boost of mRNA-1273.351 (50 mcg) and 23 with a bivalent boost of mRNA1273.351 (25 mcg ) and bivalent mRNA-1273 (25 mcg). This study assessed the immunogenicity after a third mRNA vaccination in adults who received the mRNA-1273 primary schedule approximately 9 to 10 months earlier. The booster vaccine formulations included 100 mcg of mRNA-1273, 50 mcg of mRNA1273.351 that encodes Beta variant spike protein, and a bivalent vaccine of 25 mcg each mRNA-1273 and mRNA-1273.351. The results showed that following booster vaccination, a robust response to similar titers was observed in all three groups to 614D S-2P at Day 15 [monovalent prototype 62,272 AUC (95% CI 59,973, 64,659); monovalent variant 61,373 (95% CI 58,622, 64,254); bivalent 62,025 (95% CI 59,468, 64,691). In all groups, the third dose of mRNA vaccine induced similar responses against B.1.351 [monovalent prototype 47,733 AUC (95% CI 44,932, 50,710); monovalent variant 49,768 (95% CI 46,282, 53,517); bivalent 48,126 (95% 44,728, 51,781)] that were only 20% lower than the Day 15 responses to 614D . Spike-specific CD4+ and CD8+ T cells increased to similar levels to that after the second dose.
Chalkias et al. was a phase 2/3 non-randomized trial conducted in the United States as part of a larger study registered as NCT04927065. Its aim was to evaluate the safety, reactogenicity and immunogenicity of a single booster dose of the bivalent beta-containing mRNA candidate vaccine mRNA-1273.211, in adults who received a primary schedule of mRNA-1273. The study included 300 participants who received 50 µg of mRNA-1273.211 booster, 595 participants who received 100 µg of mRNA-1273.211 booster, a historical cohort of 584 participants who received the 100 µg primary schedule and 171 participants who received a mRNA-1273 50 µg booster dose. Geometric Mean Titers (GMT) of neutralizing antibodies against the Beta variant were 953.9 (95% CI, 844.1–1,078.0) for the mRNA-1273.211 (50 µg) group and 1,574.6 (95% CI, 1,439.4–1,722.5) for the mRNA-1273.211 (100 µg) group. [Chalkias S, 2022 ]
Delta (B.1.617.2)
Lafon et al. used data from samples of 116 patients who had been vaccinated with AstraZeneca, Pfizer, or Moderna COVID-19 vaccines or had recovered from COVID-19. The study found that all the vaccines induced a neutralizing response against the Alpha variant that was higher than the wild-type virus. The mRNA vaccines generated an 82% increase in neutralizing activity, while the AstraZeneca vaccine induced a 13% increase. Responses against the Beta and Delta variants were lower for all vaccines than for wild-type viruses. Neutralizing activity against the Beta variant was 42 and 47% lower in AstraZeneca and Pfizer recipients while only 25% lower for Moderna recipients. The AstraZeneca vaccine had an 82% reduction in neutralizing activity against the Delta variant, and the Pfizer and Moderna vaccines had a decrease of 2% and 14% respectively [Lafon E, 2022 ].
Kanokudom S et al. recruited 222 adults with a complete CoronaVac regimen who received a booster dose of 15μg Pfizer-BioNTech vaccine (n=59), and 50μg Moderna vaccine (n=51), standard Pfizer-BioNTech vaccine (n=54)or standard Moderna vaccine (n=58). The booster dose induced a neutralizing response against the Delta and Omicron variants in previously seronegative participants that were not affected by dosage. On day 28 the GMT of neutralizing antibodies against the Delta variant increased to 1,505 and 2,088 in the reduced dose Pfizer-BioNTech and Moderna vaccine groups. [Kanokudom S, 2022 ].
Chuang et al. was a randomized controlled study made in Taiwan. It included data from samples of 340 health care workers (HCW) with prior Oxford-AstraZeneca homologous vaccination and that received one of the four vaccines as booster doses: Pfizer–BioNTech, half-dose Moderna, full dose Moderna or MVC-COV1901.The primary outcomes were humoral and cellular immunogenicity and the secondary outcomes safety and reactogenicity 28 days post-booster. The study found that the neutralizing activity increased significantly post boost (P < 0.0001) and the fold-rise ranged from 23.8 in MCV-COV1901 to 97.8 in mRNA1273 against the Delta variant. After each booster vaccine, the neutralization titers against the Delta variant were compatible with those of the wild type [Chih-Hsien Chuang, 2022 ].
ARNCOMBI was a randomized controlled trial conducted in France. The study included 414 individuals who received an mRNA vaccine first dose and a second dose of Pfizer-BioNTech or Moderna after 28 days. Measurement of neutralizing antibodies against the specific variants (Alpha, Beta, Delta) was performed on a representative population of 30 subjects randomly selected after stratification on vaccine schedule group, age (<40 years, ≥40 years, and <55 years, ≥55 years), and level of anti-spike IgG against the wild-type viral strains at D28 (<1000 BAU/mL, ≥1000 BAU/mL, and <5000 BAU/ml, ≥ 5000 BAU/mL). The study showed that the neutralizing antibodies titers against SARS-CoV-2 variants were not different between the homologous and heterologous vaccine groups [Janssen C, 2022 ].
Anderson et al. was a phase 2 randomized controlled trial conducted in the United States that included 96 participants with a primary schedule of Moderna: 48 with Monovalent prototype boost (100 mcg) of mRNA-1273, 25 with Monovalent variant boost of mRNA-1273.351 (50 mcg) and 23 with a bivalent boost of mRNA1273.351 (25 mcg ) and bivalent mRNA-1273 (25 mcg). This study assessed the immunogenicity after a third mRNA vaccination in adults who received the mRNA-1273 primary schedule approximately 9 to 10 months earlier. The booster vaccine formulations included 100 mcg of mRNA-1273, 50 mcg of mRNA1273.351 that encodes Beta variant spike protein, and a bivalent vaccine of 25 mcg each mRNA-1273 and mRNA-1273.351. The results showed that following booster vaccination, a robust response to similar titers was observed in all three groups to 614D S-2P at Day 15 [monovalent prototype 62,272 AUC (95% CI 59,973, 64,659); monovalent variant 61,373 (95% CI 58,622, 64,254); bivalent 62,025 (95% CI 59,468, 64,691). In all groups, the third dose of mRNA vaccine induced similar responses against B.1.351 [monovalent prototype 47,733 AUC (95% CI 44,932, 50,710); monovalent variant 49,768 (95% CI 46,282, 53,517); bivalent 48,126 (95% 44,728, 51,781)] that were only 20% lower than the Day 15 responses to 614D . Spike-specific CD4+ and CD8+ T cells increased to similar levels to that after the second dose.
Suntronwong N et al was a cohort study conducted in Thailand. 167 participants primed with heterologous CoronaVac/Oxford-AstraZeneca vaccination were enrolled to receive a booster dose of Oxford-AstraZeneca (n= 60), Pfizer-BioNTech (n= 55) of Moderna (n= 52) vaccines. This study assessed the capability of the booster vaccination to induce an increase in neutralizing antibodies and T-cell responses against SARS-CoV-2, Omicron (BA.1 and BA.2), and Delta variants. The study showed that, following the booster dose, individuals boosted with mRNA vaccines demonstrated a higher level of neutralizing activity than those boosted with Oxford-AstraZeneca [Suntronwong N, 2022 ].
Omicron (B.1.1.529.1)
Kanokudom S et al. recruited 222 adults with a complete CoronaVac regimen who received a booster dose of 15μg Pfizer-BioNTech vaccine (n=59), and 50μg Moderna vaccine (n=51), standard Pfizer-BioNTech vaccine (n=54) or standard Moderna vaccine (n=58). The booster dose induced a neutralizing response against the Delta and Omicron variants in previously seronegative participants that were not affected by dosage. On day 28 the GMTs against the Omicron variant reached 343.3 and 541.2 in the reduced dose Pfizer-BioNTech and Moderna vaccine groups. [Kanokudom S, 2022 ].
Branche A et al. recruited 602 adults with primary schedules and a single homologous or heterologous boost. The participants were randomized to six Moderna vaccine arms (50µg dose): 99 received prototype Moderna vaccine, 100 received 1 dose of Beta and Omicron BA.1 bivalent vaccine, 102 received 2 doses of Beta and Omicron BA.1 bivalent vaccine, 101 received 1 dose of Delta and Omicron BA.1 bivalent vaccine, 100 received 1 dose of Omicron BA.1 monovalent vaccine and 100 received 1 dose of Omicron BA.1 Moderna bivalent vaccine. Neutralization antibody titers (ID50) were assessed for D614G, Delta, Beta, and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination. The study found that the Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218- 4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907) [Angela R Branche, 2022 ].
Chuang et al. was a randomized controlled study made in Taiwan. It included data from samples of 340 health care workers (HCW) with prior Oxford-AstraZeneca homologous vaccination and that received one of the four vaccines as booster doses: Pfizer–BioNTech, half-dose Moderna, full dose Moderna or MVC-COV1901. The primary outcomes were humoral and cellular immunogenicity and the secondary outcomes safety and reactogenicity 28 days post-booster. The study found that the neutralizing activity increased significantly post boost (P < 0.0001) and the fold-rise ranged from 2.1 in MCV-COV1901 to 14.4 in Pfizer against the omicron variant. The neutralization titers against the omicron variant were 6.4 to 13.5 times lower than those against the wild type. All except one participant who received mRNA vaccines as a booster had detectable neutralizing antibodies against the Omicron variant [Chih-Hsien Chuang, 2022 ].
mRNA-1273-P205 was an open-label, phase 2/3 study conducted in the United States that included 819 participants with a primary schedule of Moderna: 377 included in the mRNA-1273 (50 µg) booster group, and 437 included in the mRNA-1273.24 (50 µg) Omicron BA,.1-containing bivalent vaccine group. Geometric mean titers (GMT) of neutralizing antibodies against ancestral SARS-CoV-2 (D614G) were 5977.3 (95% CI, 5321.9 -6713.3) in the mRNA-1273.214 (50 µg) group and 5649.3 (95% CI, 5056.8-6311.2) in the mRNA-1273 (50 µg) group. The adjusted GMT ratio against the ancestral strain was 1.22 (97.5% CI, 1.08-1.37) which met the prespecified criterion for noninferiority. GMT of neutralizing antibodies against Omicron were 2372.4 (95% CI, 2070.6-2718.2) in the mRNA-1273.214 (50 µg) group and 1473.5 (95% CI, 1270.8-1708.4) in the mRNA-1273 (50 µg) group. Adjusted GMT ratio against Omicron was 1.75 (97.5% CI, 1.49-2.04) which met the prespecified criterion for noninferiority. The percentages of participants with a seroresponse against ancestral SARS-CoV-2 (D614G) were 100% (95% CI, 98.9% to 100%) for mRNA1273.214 and 100% (95% CI, 98.6% to 100%) for mRNA-1273 at 28 days after the booster doses, with an estimated difference of 0, which met the noninferiority criterion. [Chalkias S, 2022 ]
mRNA-1273-P205 was an open-label, phase 2/3 study conducted in the United States that included 887 participants with a primary schedule of Moderna and a first homologous booster: 176 received a second booster dose of mRNA-1273 (50 µg) and 511 received a second booster dose of the omicron BA.4/BA.5-containing mRNA-1273.222 (50 µg) vaccine. Geometric mean titers (GMT) of neutralizing antibodies against the ancestral SARS-CoV-2 (D614G) strain were 7322.4 (95% CI, 6386.2-8395.7), and 5651.4 (95% CI, 5055.7-6317.3) for mRNA-1273.222 (50 µg) and mRNA-1273 (50 µg), respectively. GMT of neutralizing antibodies against Omicron were 2324.6 (95% CI, 1921.2-2812.7), and 488.5 (95% CI, 427.4-558.4) for mRNA-1273.222 (50 µg), and mRNA-1273 (50 µg), respectively. [Spyros Chalkias, 2022 ]
SWITCH ON was an open-label randomized trial conducted in the Netherlands that included 187 healthcare workers: 42 with Ad26.COV2.S primary schedule and BNT162b2 Omicron BA.1 booster, 45 with Ad26.COV2.S primary schedule and mRNA-1273.214 Omicron BA.1 booster, 44 with mRNA-based primary schedule and BNT162b2 Omicron BA.1 booster and 56 mRNA-based primary schedules and mRNA-1273.214 Omicron BA.1 booster. The aim was to assess the fold change in S1-specific IgG antibodies before and 28 days after booster vaccination. Fold change of S1-specific binding antibody levels between baseline and 28 days after bivalent booster vaccination was 2.9, 3.6, 4.3, and 3.5-fold for participants with Ad26.COV2.S+BNT162b2 Omicron BA.1 booster, mRNA-based primary schedule+BNT162b2 Omicron BA.1 booster, Ad26.COV2.S+mRNA-1273.214 Omicron BA.1 booster, and mRNA-based primary schedule+mRNA-1273.214 Omicron BA.1 booster, respectively. [Ngoc Tan, 2022 ]
Prasert Assantachai et al was a randomized controlled trial conducted in Thailand that included 210 participants aged ≥65 years with AstraZeneca primary schedule: 35 received intradermal mRNA-1273, 35 intramuscular mRNA-1273, 70 intradermal BNT162b2, and 70 intramuscular BNT162b2. The group that reported the highest geometric mean titers against the ancestral strain and Omicron BA.1 variant was the group that received the intramuscular mRNA-1273 vaccine (GMT 1,717.9 and 617), followed by the group that received the intradermal mRNA-1273 vaccine (GMT 1,212 and 318), the group that received the intramuscular BNT162b2 vaccine (GMT 713 and 230 and the group that received the intradermal BNT162b2 vaccine (GMT 587 and 148), respectively. [Prasert Assantachai, 2022 ].
Lee I et al was a phase 3 randomized trial conducted in the United Kingdom that assessed the immunogenicity and safety of 50 µg doses of Omicron BA.1- monovalent mRNA1273.529 and bivalent mRNA-1273.214 booster vaccines compared with 50 µg mRNA-1273. Neutralizing antibody geometric mean concentrations against Omicron BA.1 were 537.7 (95% CI, 478.2−604.6) for mRNA-1273.529 booster and 307.4 (95% CI, 279.5−338.2) for mRNA-1273 booster [Lee, I. T., 2023 ].
Effectiveness outcomes
Alpha (B.1.1.7)
Nasreen et al. was a case-control study (test-negative) conducted in Canada. The study included 421,073 SARS-CoV-2-positive symptomatic cases (707 with Alpha variant receive 1 or 2 doses of Moderna) and 351,540 SARS-CoV-2-negative symptomatic controls. The study evaluates the effectiveness of mRNA-1273 vaccines against symptomatic SARS-CoV-2 infection and severe outcomes caused by the Alpha (B.1.1.7) variant, from December 2020 to May 2021. Effectiveness against symptomatic infection was 92% (95% CI, 86–96%) and effectiveness against hospitalization or death was 94% (95% CI, 89–97%). [Nasreen, S., 2021 ].
Fabiani M et al conducted a comparative cohort study in Italy that included 33,250,344 individuals aged ≥16 years who received the first dose of BNT162b2 (Pfizer-BioNTech) or mRNA1273 (Moderna) vaccine and did not have a previous diagnosis of SARS-CoV-2 infection. The aim of the study was to estimate the effectiveness of mRNA vaccines against SARS-CoV-2 infection and severe covid-19 at different times after vaccination during predominant circulation of the delta variant. The results showed vaccine effectiveness against infection during the Alpha variant predominance period (aggregated data from 2 mRNA vaccines: Pfizer and Moderna) was 79.0% (95% CI 76.8 to 80.9), >14 days after the second dose. Furthermore, Vaccine effectiveness against severe infection during Alpha variant predominance period (aggregated data from 2 mRNA vaccines: Pfizer and Moderna) was 89.4% (95 CI 87.6 to 91.0), > 14 days after second dose [Fabiani M, 2022 ].
Delta (B.1.617.2)
Nasreen et al. was a case-control study (test-negative) conducted in Canada. The study included 421,073 SARS-CoV-2 positive symptomatic cases (participants ≤61 years of age with Delta variant infection receive 1 or 2 doses of Moderna) and 351,540 SARS-CoV- 2 negative symptomatic controls. The study evaluates the efficacy of the Moderna COVID-19 vaccine against the symptomatic infection of SARS-CoV-2 and the serious outcomes caused by the Delta variant (B.1.617.2) during December 2020 to May 2021. Effectiveness against symptomatic infection was 72% (95% CI, 57–82%) and effectiveness against hospitalization or death was 96% (95% CI, 72 to 99%) [Nasreen, S., 2021 ].
Accorsi EK et al included 23 391 cases and 46 764 controls (3 doses= 12 476; 2 doses=19839; Unvaccinated= 17 177). Data were collected ≥14 days after dose 3 and ≥6 months between doses 2 and 3. The study showed that receiving three doses of Moderna COVID-19 vaccine compared to not receiving any or receiving only two doses, was associated with protection against both the Omicron and Delta. Comparison of 3 Doses vs Unvaccinated showed for Omicron variant OR 0.28 (95% CI 0.26 to 0.31) and for Delta variant OR 0.045 (95% CI 0.038 to 0.053). Comparison of 3 doses versus 2 doses showed for Omicron variant OR 0.31 (95% CI 0.28 to 0.34) and for Delta variant OR 0.13 (95% CI 0.11 to 0.15) [Accorsi EK, 2022 ].
Buchan et al. conducted a test-negative case-control study using linked provincial databases for SARS-CoV-2 laboratory testing, reportable disease, COVID-19 vaccination and health administration in Ontario (Canadá) to estimate the vaccine effectiveness (VE) against symptomatic infections and severe outcomes associates with these infections. Of 134,435, 4261 were Delta-positive cases, and 114 087 were test-negative controls. VE against Delta symptomatic infection: 97% (95% CI 95-98). VE against Delta severe outcome:100% (95% CI 98-100). [Buchan SA, 2022 ]
Johnson AG et al was a cohort study conducted in the United States. The study enrolled 6,812,040 COVID-19 cases in unvaccinated persons and 2,866,517 cases in fully vaccinated persons. Data were collected between April 4, 2021, and December 25, 2021. During periods of Delta and Omicron variant emergence. The protection against infection during the Delta predominant period (October-November) was higher among booster recipients, especially among persons over 50 years of age. The average weekly IRR was 4.6 (95% CI 4.2 to 5.1) for the group without a booster and IRR 17.4 (95% CI 14.5 to 21.1) for the booster group.[Johnson AG, 2022 ]
The VISION Network study included 222,772 encounters from 383 emergency departments (ED) and urgent care (UC), and 87,904 hospitalizations from 259 hospitals. Data were collected during periods of Delta and Omicron variant predominance between august 2021 to and January 2022. Based on all results combined, during the Delta-predominant period, vaccine effectiveness against Lab-confirmed COVID-19 was significantly lower among patients who received the second dose ≥180 days earlier (76%; 95% CI 75 to 77) than among those who received the third dose (94%; 95% CI 93 to 94). In the omicron-predominant period, vaccine effectiveness against the same outcome was significantly lower among those who received the second dose ≥180 days earlier (38%; 95% CI 32 to 43) than those who received the third dose (82%; 95% CI 79 to 84). [Thompson MG, 2022 ]
Fabiani M et al conducted a comparative cohort study in Italy that included 33,250,344 individuals aged ≥16 years who received the first dose of BNT162b2 (Pfizer-BioNTech) or mRNA1273 (Moderna) vaccine and did not have a previous diagnosis of SARS-CoV-2 infection. The aim of the study was to estimate the effectiveness of mRNA vaccines against SARS-CoV-2 infection and severe covid-19 at different times after vaccination during predominant circulation of the delta variant. The results showed vaccine effectiveness against infection during the Delta variant predominance period (aggregated data from 2 mRNA vaccines: Pfizer and Moderna) was 69% (95% CI 66.7 to 71.2), >14 days after the second dose. Furthermore,Vaccine effectiveness against severe infection during Delta variant predominance period (aggregated data from 2 mRNA vaccines: Pfizer and Moderna) was 91.1% (95% CI 89.7 to 92.2), > 14 days after second dose [Fabiani M, 2022 ].
Kislaya I et al. was a case-control study conducted in Portugal. The study enrolled 15,001 participants, 3,737 were eligible for a booster dose of Pfizer-BioNTech or Moderna. Based on data from RT-PCR SARS-CoV-2 positive cases were notified in the mandatory National Epidemiological Surveillance Information System (SINAVE) in Portugal from December 6 to 26, 2021. The effectiveness against the Delta variant was 62.5% (95% CI: 61 to 63.9) for the primary scheme and 94% (95% CI: 93.4 to 94.6) for the booster [Irina Kislaya, 2022 ].
Andrews N et al. was a case-control study conducted in England. The study enrolled 2,663,549 vaccinated participants: 204,154 cases for Delta variant, 886,774 cases for Omicron variant and 1,572, 621 test-negative controls. The study analyzed information from national databases, Pillar 1, Pillar 2, NIMS and NHS regarding Covid-19 vaccination, testing, and variants from November 25, 2021, through January 12, 2022. Moderna effectiveness against Delta variant for symptomatic infection was 57.4% (95% CI 52.6 to 61.8) 4 weeks after the first dose, 80.4% (95% CI 67.3 to 88.2) 25 weeks after the second dose, 94.7% (95% CI 89.3 to 97.3) 2-4 weeks after a Pfizer-BioNTech booster and 96.4% (95% CI 91.4 to 98.5) 2-4 weeks after Moderna booster [Andrews N, 2022 ].
Young-Xu Y et al. was a case-control study with matched test-negative design conducted in the United States. The study used records and COVID-19 laboratory test data from the Veterans Health Administration (VHA), which includes 1,293 healthcare facilities that attend US veterans. Positive tests during November 2021 were presumed to be delta SARS-CoV-2 infections. Each case (positive test) was matched with up to four controls (negative tests). Vaccine effectiveness was estimated through the number of infections, hospitalizations, and death within 30 days of a positive test. The vaccine effectiveness (VE) against delta infection after two mRNA vaccine doses was 54% (95% CI 50 to 57) and increased to 90% (95% CI 88 to 92) after the booster mRNA dose. The VE against hospitalizations was 75% (95% CI 69 to 80) after two mRNA vaccine doses and increased to 94% (95% CI 90 to 96) after the booster mRNA dose. The VE against death after two mRNA vaccine doses was 95% (95% CI 85 to 97) and was similar after the booster mRNA dose (96%; 95% CI 87 to 99) [Young-Xu Y, 2022 ].
Buchan et al. conducted a test-negative case-control study using linked provincial databases for SARS-CoV-2 laboratory testing, reportable disease, COVID-19 vaccination and health administration in Ontario (Canadá) to estimate the vaccine effectiveness (VE) against symptomatic infections and severe outcomes associates with these infections. Of 134,435 total participants (> 18 years older), 4261 were Delta-positive cases (mean [SD] age, 44.2 [16.8] years; 2199 [51.6%] female), and 114 087 were test-negative controls (mean [SD] age, 42.0 [16.5] years; 7 884 [59.5%] female). Symptomatic Infection DELTA (VE %, 95% CI) BNT16b2: 97 (96-98) and mRNA-1273: 97 (95-98). Severe Outcome DELTA (VE %, 95% CI) BNT16b2: 99 (98-99) and mRNA-1273: 100 (98-100). [Buchan SA, 2022 ]
Ferdinands JM et al was a test-negative case-control study conducted in United States. The study included data from 259,006 hospital admissions: 213,103 with SARS-CoV-2 negative test and 45,903 with SARS-CoV-2 positive test. The main outcome was waning of vaccine effectiveness with BNT162b2 or mRNA-1273 vaccine during the omicron and delta periods. Vaccine effectiveness (VE) against COVID-19-associated hospitalizations during the Delta-predominant period for Moderna vaccine was 98% (95% CI, 97-99) (less than two months after the second dose) and 97% (95% CI, 96-98) with the third booster dose. [Ferdinands JM, 2022 ]
Rennert L. was an observational study conducted in the United States that included 21,261 university students undergoing repeated surveillance testing during which Delta was the dominant SARS-CoV-2 variant. The estimated Moderna vaccine effectiveness against any SARS-CoV-2 infection was 75.4% (95% CI, 70.5-79.5). Between 0 and 6 months post-vaccination, the estimated protection decreased from 88.9% to 58.3% for mRNA-1273 vaccine. [Rennert L, 2022 ]
Castelli JM et al was a test-negative case-control study conducted in Argentina that included 844,460 children and adolescents without previous SARS-CoV-2 infection eligible to receive a primary vaccination schedule. The aim was to assess the effectiveness of different combinations of mRNA vaccines in children and adolescents. Vaccine effectiveness (VE) for the Pfizer/Moderna heterologous schedule was 88.9% (95% CI, 66.1% to 96.4%) during the Delta predominance period. VE for the Moderna primary schedule was 70.2% (95% CI, 66.8 to 73.1) during the Delta predominance period. [Castelli JM, 2022 ]
Yuanyuan F et al. was an observational study to analyze vaccination status and SARS-CoV-2 infection data from more than 10.4 million participants in the national COVID Cohort Collaborative during an 18-month-period (December 2020 to June 2022) in the United States. Vaccine Effectiveness (VE) against COVID-19 infection during the Delta predominance period was 47.64% (95% CI, 45.47% to 49.73%) for the Moderna/Moderna/Moderna schedule, 36.15% (95% CI, 29.02% to 42.56%) for the Moderna/Moderna/Pfizer schedule, and 34.19% (95% CI, 26.21% to 41.3%) for the Pfizer/Pfizer/Moderna schedule. VE against COVID-19-related death during the Delta predominance period was 91.87% (95% CI, 84.88% to 95.63%) for the Pfizer/Pfizer/Moderna schedule, 81.09% (95% CI, 79.17% to 82.85%) for the Moderna/Moderna/Moderna schedule, and 83.99% (95% CI, 77.19% to 88.76%) for the Moderna/Moderna/Pfizer schedule. [Yuanyuan Fu, 2022 ]
Rane MS et al was a case control study conducted in the United States that included data from 931,972 patients with vaccine records: 39,185 with a positive test and 892,787 with a negative test. The study estimated Vaccine Effectiveness (VE) against symptomatic infection in a population of patients seeking care at CityMD, a large ambulatory care center in New York and neighboring areas. VE against symptomatic infection for the BioNTech BNT162b and mRNA-1273 vaccines combined was 96% (95% CI, 95% to 97%) in pre-Delta period and 79% (95% CI, 77% to 81%) in the Delta period. Adjusted VE against any infection was higher in all subgroups in the pre-Delta period compared with the Delta period. VE for participants aged 12 to 15 years was 85% (95% CI, 81% to 88%) during the Delta period. VE was lower for adults aged 64 years and older compared to <64 years, even in the pre-Delta period. [Rane MS, 2022 ]
Huiberts A et al. was a prospective cohort study conducted in Netherlands that included 27,646 participants from the Omicron period: 3,802 received primary vaccination schedule, 23,352 received first booster dose and 492 were unvaccinated. The primary outcome was contracting SARS-CoV-2 between July 12th 2021 and June 6th 2022. Vaccine effectiveness (VE) against contracting COVID-19 during the Omicron BA.1-2 period was 15.8% (95% CI, -26.3% to 43.9%), 68.3% (95% CI, 63.1% to 72.8%) and 67.6% (95% CI, 60.1% to 73.7%) for Moderna primary schedule, mRNA primary schedule with Moderna booster and AstraZeneca primary schedule with Moderna booster, respectively. VE against contracting COVID-19 during the Delta period was 100% (95% CI, 0% to 100%) and 100% (95% CI, 0% to 100%) for Moderna primary schedule and mRNA primary schedule with Moderna booster, respectively. [Anne J. Huiberts, 2023 ]
Omicron (B.1.1.529.1)
Accorsi EK et al included 23 391 cases and 46 764 controls (3 doses= 12 476; 2 doses=19839; Unvaccinated= 17 177). Data were collected ≥14 days after dose 3 and ≥6 months between doses 2 and 3. The study showed that receiving three doses of Moderna COVID-19 vaccine compared to not receiving any or receiving only two doses, was associated with protection against both the Omicron and Delta. Comparison of 3 Doses vs Unvaccinated showed for Omicron variant OR 0.28 (95% CI 0.26 to 0.31) and for Delta variant OR 0.045 (95% CI 0.038 to 0.053). Comparison of 3 doses versus 2 doses showed for Omicron variant OR 0.31 (95% CI 0.28 to 0.34) and for Delta variant OR 0.13 (95% CI 0.11 to 0.15) [Accorsi EK, 2022 ].
Buchan et al. conducted a test-negative case-control study using linked provincial databases for SARS-CoV-2 laboratory testing, reportable disease, COVID-19 vaccination and health administration in Ontario (Canadá) to estimate the vaccine effectiveness (VE) against symptomatic infections and severe outcomes associates with these infections. Of 134,435 total participants (> 18 years older), 16,087 were Omicron-positive cases , and 114 087 were test-negative controls. VE against Omicron symptomatic infection: 65% (95% CI 55-72). VE against Omicron severe outcome: 93% (95% CI 74-98). [Buchan SA, 2022 ]
Chemaitelly H et al was a case-control study conducted in Qatar, based on data from a test-negative design study that seeks to assess the duration of protection of Pfizer-BioNTech after the second dose and after third/booster dose against symptomatic Omicron infection and against COVID-19 hospitalization and death, between December 23, 2021, and February 2, 2022. Vaccine effectiveness was 53.1% (95% CI 40.7 to 62.8) 2 to 3 weeks after receiving the booster dose [Hiam Chemaitelly, 2022 ].
Johnson AG et al was a cohort study conducted in the United States. The study enrolled 6,812,040 COVID-19 cases in unvaccinated persons and 2,866,517 cases in fully vaccinated persons. Data were collected between April 4, 2021, and December 25, 2021. During periods of Delta and Omicron variant emergence. The protection against infection during the Delta predominant period (October-November) was higher among booster recipients, especially among persons over 50 years of age. The average weekly IRR was 4.6 (95% CI 4.2 to 5.1) for the group without a booster and IRR 17.4 (95% CI 14.5 to 21.1) for the booster group.[Johnson AG, 2022 ]
The VISION Network study included 222,772 encounters from 383 emergency departments (ED) and urgent care (UC), and 87,904 hospitalizations from 259 hospitals. Data were collected during periods of Delta and Omicron variant predominance between august 2021to and January 2022. Based on all results combined, during the Delta-predominant period, vaccine effectiveness against Lab-confirmed COVID-19 was significantly lower among patients who received the second dose ≥180 days earlier (76%; 95% CI 75 to 77) than among those who received the third dose (94%; 95% CI 93 to 94). In the omicron-predominant period, vaccine effectiveness against the same outcome was significantly lower among those who received the second dose ≥180 days earlier (38%; 95% CI 32 to 43) than those who received the third dose (82%; 95% CI 79 to 84)[Thompson MG, 2022 ].
Shrestha NK et al. was a cohort study conducted in the United States, based on data from Cleveland Clinic Health System in Ohio, United States; all employees who had been vaccinated (with either Pfizer-BioNTech or Moderna) or had previous COVID-19 infection by November 26, 2021, were included. With a follow-up period of 90 days. The vaccine effectiveness during the Omicron surge was 57% (95%CI: 54% to 59%) for the complete scheme and a booster of mRNA vaccine [Nabin K Shrestha, 2022 ].
Kislaya I et al. was a case-control study conducted in Portugal. The study enrolled 15,001 participants; 3.737 were eligible for a booster dose of Pfizer-BioNTech or Moderna. Based on data from RT-PCR SARS-CoV-2 positive cases were notified in the mandatory National Epidemiological Surveillance Information System (SINAVE) in Portugal from December 6 to 26, 2021. The effectiveness against the Delta variant was 62.5% (95% CI: 61 to 63.9) for the primary scheme and 94% (95% CI: 93.4 to 94.6) for the booster [Irina Kislaya, 2022 ].
Abu-Raddad LJ et al. was a study conducted in Qatar including data from 2,239,193 vaccinated individuals: 1,299,010 with Pfizer-BioNTech and 890,619 with Moderna. The study also included matched unvaccinated controls. The study analyzed information from national, federated databases regarding Covid-19 vaccination, laboratory testing, hospitalization, and death from December 19, 2021, through January 26, 2022. The vaccine effectiveness against the Omicron variant of the booster dose compared to the two-dose regimen was 47.3% (95% CI 40.7 to 53.3) for symptomatic infection [Abu-Raddad LJ, 2022 ].
Andrews N et al. was a case-control study conducted in England. The study enrolled 2,663,549 vaccinated participants: 204,154 cases for Delta variant, 886,774 cases for Omicron variant and 1,572, 621 test-negative controls. The study analyzed information from national databases, Pillar 1, Pillar 2, NIMS and NHS regarding Covid-19 vaccination, testing, and variants from November 25, 2021, through January 12, 2022. Moderna effectiveness against Delta variant for symptomatic infection was 57.4% (95% CI 52.6 to 61.8) 4 weeks after the first dose, 80.4% (95% CI 67.3 to 88.2) 25 weeks after the second dose, 94.7% (95% CI 89.3 to 97.3) 2-4 weeks after a Pfizer-BioNTech booster and 96.4% (95% CI 91.4 to 98.5) 2-4 weeks after Moderna booster [Andrews N, 2022 ].
Young-Xu Y et al. was a case-control study with matched test-negative design conducted in the United States. The study used records and COVID-19 laboratory test data from the Veterans Health Administration (VHA), which includes 1,293 healthcare facilities that attend US veterans. Positive tests during January 2022 were presumed to be Omicron SARS-CoV-2 infections. Each case (positive test) was matched with up to four controls (negative tests). Vaccine effectiveness was estimated through the number of infections, hospitalizations, and death within 30 days of a positive test. The vaccine effectiveness (VE) against omicron infection after two mRNA vaccine doses was 12% (95% CI 10 to 15) and increased to 64% (95% CI 63 to 65) after the booster mRNA dose. The VE against hospitalizations was 63% (95% CI 58 to 67) after two mRNA vaccine doses and increased to 89% (95% CI 88 to 91) after the booster mRNA dose. The VE against death after two mRNA vaccine doses was 77% (95% CI 67 to 83) and after the booster mRNA dose increased to 94% (95% CI 90 to 96) [Young-Xu Y, 2022 ].
Ng OT et al was cohort study conducted in Singapore. The study included 2,441,581 eligible individuals. It was based on data from the Singapore Ministry of Health’s (MOH) official COVID-19 database, including individuals who had received 2 or 3 doses of mRNA vaccines (by Pfizer-BioNTech or Moderna) or inactivated vaccines (by Sinovac or Sinopharm) and notified infections from December 27th 2021 to March 10th 2022. Risk Infeccion (Incidence Rate Ratios) was 0.67% (95% CI 0.62 to 0.72) and 1.16% (95% CI 0.82 to 1.65) against Severe COVID Infeccion (Aggregated data from Moderna and Pfizer COVID-19 vaccines). [Ng OT, 2022 ]
Buchan et al. conducted a test-negative case-control study using linked provincial databases for SARS-CoV-2 laboratory testing, reportable disease, COVID-19 vaccination and health administration in Ontario (Canadá) to estimate the vaccine effectiveness (VE) against symptomatic infections and severe outcomes associates with these infections. Of 134,435 total participants (> 18 years older), 16,087 were Omicron-positive cases (mean [SD] age, 36.0 [14.1] years; 8249 [51.3%] female), and 114 087 were test-negative controls (mean [SD] age, 42.0 [16.5] years; 7 884 [59.5%] female). Symptomatic Infection OMICRON (VE %, 95% CI) BNT16b2: 60 (55-65) and mRNA-1273: 65 (55-72). Severe Outcome OMICRON (VE %, 95% CI) BNT16b2: 95 (87-98) and mRNA-1273: 93 (74-98). [Buchan SA, 2022 ]
Lin DY et al, was a comparative cohort study conducted in the USA. The study included 10,600,823 individuals, among which were 2,771,364 cases of COVID-19. IBased on data from the North Carolina COVID-19 Surveillance System and the Covid-19 Vaccine Management System, including data from residents of North Carolina from December 11, 2020, to September 8, 2021. Vaccine effectiveness of 2 doses of Moderna was 59% (95% CI 57.7% to 60.3%], when the Omicron variant emerged. [Lin DY, 2022 ].
González S et al was a retrospective cohort study conducted in Argentina including 1,536,435 participants: 689,552 in the BIBP vaccine group and 846,883 in mRNA vaccine group (539,093 with Pfizer/Pfizer schedule, 15,552 with Pfizer/Moderna schedule and 44,862 with Moderna/Pfizer schedule. mRNA-1273 and BNT162b2 vaccines were administered to 12−17- year subjects; and BBIBP-CorV to 3−11-year subjects. Vaccine effectiveness for the mRNA vaccine group was 80.0% (95% CI 64.3 to 88.0) for the 12−17 age (mRNA vaccines) subgroup. [González S, 2022 ]
Risk M et al was a retrospective cohort study conducted in the United States including 168,414 participants: 133,238 vaccinated with mRNA vaccines and 35,176 unvaccinated. Based on data from the Michigan Medicine health-care system, the Michigan State Registry and chart-reviewed COVID-19 hospitalization data. Including patients 18 years old and above, who received mRNA based COVID-19 vaccines. During the Omicron dominant period December 2021 to March 2022. The effectiveness of the Moderna vaccine during the Omicron period in immunocompetent participants was 16% (95%CI 5 to 26) for two doses and 57% (95%CI 51 to 62) for three doses. In immunocompromised participants the effectiveness was 57% (95%CI 29 to 74) for two doses and 60% (95%CI 42 to 73) for three doses. [Risk M, 2022 ]
Monge S et al, was a nationwide Cohort study conducted in Spain. This study included 7,036,433 participants older than 40 years: 3,111,159 in the booster group and 3,111,159 in the no booster group. The aim of this study was to estimate the effectiveness of mRNA-based vaccine boosters against infection during the period of the predominance of the omicron variant in Spain. Vaccine effectiveness with Moderna booster and AstraZeneca, JAnssen, Moderna or Pfizer primary schedule was 52,5% (95% CI, 51,3–53,7). Vaccine effectiveness of Moderna primary schedule and ARNm booster was 55.3% (95% CI, 52.3–58.2) (Moderna or Pfizer booster dose). [Monge S, 2022 ]
Ferdinands JM et al was a test-negative case-control study conducted in United States. The study included data from 259,006 hospital admissions: 213,103 with SARS-CoV-2 negative test and 45,903 with SARS-CoV-2 positive test. The main outcome was waning of vaccine effectiveness with BNT162b2 or mRNA-1273 vaccine during the omicron and delta periods. Vaccine effectiveness (VE) against COVID-19-associated hospitalizations during the Omicron-predominant period for Moderna vaccine was 87% (95% CI, 75-93) (less than two months after the second dose) and 91% (95% CI, 89-92)
with the third booster dose. [Ferdinands JM, 2022 ]
Ioannu et al. was a retrospective matched-cohort study conducted in the United States. The study included 981,676 participants: 490,838 boosted individuals and 490,838 non-boosted individuals. Based on data from the Veterans Association's (VA) Corporate Data Warehouse, a database of VA enrollees' comprehensive electronic health records, and the VA COVID-19 Shared Data Resource. It included patients 18 years old and above, who received mRNA based COVID-19 boosters and a matched cohort of participants that did not, during the Omicron dominant period between December 2021 and March 2022. The effectiveness of the Moderna vaccine booster during the Omicron dominance period was 44.6% (95% CI, 42.5-46.6) against infection and 52.9% (95% CI, 45.6-59.2) against hospitalization. [Ioannou GN, 2022 ]
Grewal R et al. was a case-control study (test negative design) conducted in the United States. The aim of this study was to estimate the marginal effectiveness of a fourth versus third dose and the vaccine effectiveness of the mRNA COVID-19 vaccines BNT162b2 and mRNA-1273 against any infection, symptomatic infection, and severe outcomes (hospital admission or death) related to the Omicron variant. Vaccine effectiveness of three doses of the Moderna vaccine against the Omicron variant to any infection was 44% (95% CI, 38% to 49%), against symptomatic infection was 61% (95% CI, 50% to 69%) and against severe outcomes 81% (95% CI, 74% to 86%). [Grewal R, 2022 ].
Agrawal et al was a retrospective cohort study conducted in the United Kingdom that included 16,208,600 participants, of which 7,589,080 received a Pfizer-BioNTech primary schedule and 8,619,520 received a ChAdOx1 primary schedule. The study was based on data from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database, Vaccine Management System, Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II), and Secure Anonymised Information Linkage Databank platform, during the Omicron period, between December 2021 and February 2022. The adjusted Rate Ratio (aRR) 3-5 weeks after booster vaccination against hospitalization was 0.58 (95% CI, 0.46-0.73) for the Pfizer-BioNTech primary schedule and Moderna booster group, and 0.41 (95% CI, 0.33-0.50) for the ChAdOx1 primary schedule and Moderna booster group. [Agrawal U, 2022 ]
Hung FT et al was a case-control study conducted in the United States that included 123,236 participants, 30,809 cases and 92,427 controls. Based on data from KPSC electronic health records, California Immunizations Registry (CAIR) and Care Everywhere, during the Omicron predominance period (between January and June 2022). The study assessed the effectiveness of 3 and 4 doses of the mRNA-1273 vaccine against SARS-CoV-2 Omicron variants. The adjusted vaccine effectiveness against infection 14-30 days after the third dose against the BA.4 variant was 72.6% (95% CI, -54.7% to 96.6%) and against the BA.5 variant was 90.6% (95% CI, 30.6% to 98.7%). Vaccine effectiveness after the fourth dose against BA.4: 75.7% (95% CI, 44.7% to 91%) and 30.8% (95% CI, -9.2% to 56.5%) against BA.5. The adjusted effectiveness against hospitalization after the third dose against BA.4/BA.5 was 72.4% (95% CI, 23.9% to 90%), and 88.5% (95% CI, 51.8% to 97.2%) after the fourth dose. [Hung Fu Tseng, 2022 ]
Baum U et al was a cohort study conducted in Finland including 896,220 participants aged 70 years and older. The study was based on a nationwide register-based cohort, between December 27th 2020 and March 31st 2022. Vaccine effectiveness (VE) against hospital admission during the Omicron period was 79% (95% CI, 43% to 92%) for the primary schedule, 96% (95% CI, 91% to 98%) for the Moderna schedule+Moderna booster, 91% (95% CI, 87% to 94%) for the Pfizer schedule + Moderna booster, 92% (95% CI, 80% to 97%) for the Moderna schedule + Pfizer Booster, and 94% (95% CI, 81% to 98%) for the AstraZeneca schedule + Moderna booster. [Baum U, 2022 ]
Castelli JM et al was a test-negative case-control study conducted in Argentina that included 844,460 children and adolescents without previous SARS-CoV-2 infection eligible to receive a primary vaccination schedule. The aim was to assess the effectiveness of different combinations of mRNA vaccines in children and adolescents. Vaccine effectiveness (VE) for the Pfizer/Moderna heterologous schedule was 40.6% (95% CI, 29.4% to 50.0%) during the Omicron predominance period. VE for the Moderna primary schedule was 17.9% (95% CI, 14.0% to 21.5%) during the Omicron predominance period. [Castelli JM, 2022 ]
Intawong K et al was a test-negative case-control study conducted in Thailand that included 36,170 participants, 14,682 cases and 21,488 controls. Based on data from the Epid-CM platform, including participants aged 18 years and older, between October 2021 and April 2022.The aim was to assess the effectiveness of different booster doses. The adjusted vaccine effectiveness (VE) against infection during the Omicron predominance period after the third dose was 31% (95% CI, 15% to 44%) for the Pfizer-BioNTech booster, 26% (95% CI, 8% to 40%) for the AstraZeneca booster and 31% (95% CI, 13% to 45%) for the Moderna booster. The adjusted VE after the fourth dose was 71% (95% CI, 60% to 79%) for the Pfizer-BioNTech booster, 73% (95% CI, 48% to 89%) for the AstraZeneca booster and 71% (95% CI, 59% to 79%) for the Moderna booster. [Intawong K, 2022 ]
Grewal R was a case-control study conducted in Canada that included data from 3,736 Omicron positive cases and 77,695 SARS-CoV-2 negative controls. The aim was to estimate the effectiveness of a fourth dose of an mRNA vaccine against Omicron infections and severe outcomes over time. Vaccine effectiveness (VE) against symptomatic infection was 51% (95% CI, 42% to 60%), and 69% (95% CI, 61% to 75%) after the third and fourth doses, respectively. VE against severe outcomes was 77% (95% CI, 68% to 83%), and 79% (95% CI, 71% to 84%) after the third and fourth doses, respectively. [Grewal R, 2022 ]
Huiberts A et al. was a prospective cohort study conducted in Netherlands that included 27,646 participants from the Omicron period: 3,802 received primary vaccination schedule, 23,352 received first booster dose and 492 were unvaccinated. The primary outcome was contracting SARS-CoV-2 between July 12th 2021 and June 6th 2022. Vaccine effectiveness (VE) against contracting COVID-19 during the Omicron BA.1-2 period was 15.8% (95% CI, -26.3% to 43.9%), 68.3% (95% CI, 63.1% to 72.8%) and 67.6% (95% CI, 60.1% to 73.7%) for Moderna primary schedule, mRNA primary schedule with Moderna booster and AstraZeneca primary schedule with Moderna booster, respectively. VE against contracting COVID-19 during the Delta period was 100% (95% CI, 0% to 100%) and 100% (95% CI, 0% to 100%) for Moderna primary schedule and mRNA primary schedule with Moderna booster, respectively. [Anne J. Huiberts, 2023 ]
Tseng HF et al was a test negative case control study conducted in United States. This study included data from 123,236 participants: 30,809 with a SARS-CoV-2 positive test and 92,427 with SARS-CoV-2 negative test. This study assessed vaccine effectiveness against infection and hospitalization with omicron sub-variants. Adjusted vaccine effectiveness against hospitalization for Omicron sub-variants for 3 doses was 97.5% (95% CI, 96.3% to 98.3%), 82% (95% CI, 64.5% to 90.8%) and 72.4% (95% CI, 23.9% to 90.0%) for BA.1, BA.2 and BA.4/BA.5 sub-variants, respectively. Adjusted vaccine effectiveness against hospitalization for Omicron sub-variants for 4 doses was 96.4% (95% CI, 88.4% to 98.9%) and 88.5% (95% CI, 51.8% to 97.2%) for BA.2 and BA.4/BA.5 sub-variants, respectively. [Tseng HF, 2023 ]
Cerqueira-Silva T et al was a case-control study, test-negative design, conducted in Brazil and Scotland. The study included 5,832,210 participants: 5,276,385 from Brazil and 555,825 from Scotland. This study assessed vaccine effectiveness of a mRNA booster after AstraZeneca or Pfizer primary schedule during the period of Omicron dominance. Vaccine effectiveness against severe outcomes was 93.5% (95% CI, 93% to 94%), 94.4% (95% CI, 87.7% to 97.5%) and 92.7% (95% CI, 91% to 94%) with AstraZeneca primary schedule and Pfizer booster, AstraZeneca primary schedule and Moderna booster, and Pfizer homologous booster, respectively. [Cerqueira-Silva T, 2023 ]
Weng C et al was a comparative study conducted in United States that included 38,602 participants: 22,247 with at least one SARS-CoV-2 PCR test. The aim was to assess mRNA vaccine effectiveness (VE) in preventing SARS-CoV-2 infections. Adjusted VE of 2 doses of Moderna was 97.5% (95% CI, 82.5% to 99.7%). Adjusted VE against Omicron (2 doses of Moderna) was 25.6% (95% CI, 10.7% to 39.0%). Adjusted VE against Omicron (3 doses of Moderna) was 71.2% (95% CI, 24.0% to 90.8%). [Weng CH, 2023 ]
Vella et al was a cohort study conducted in Italy that included 913,382 participants: 456,690 received 2 doses and 456,692 received a booster (3 doses). Based on data from the Sicilian Regional Health Office, from January 1st to March 31st 2022. The study included all residents in Sicily aged ≥ 18 years without previous SARS-CoV-2 infection and with a complete mRNA vaccine primary cycle. Vaccine effectiveness of the booster dose was 74.7% (95% CI, 72.7% to 76.7%) against infection, 79.7% (95% CI, 77.2% to 82.1%) against severe disease and 73.1% (95% CI, 70.6% to 75.7%) against intubation/death. [Vella G, 2023 ]
Tenforde MW et al was a case-control study conducted in the United States that included data from 78,170 emergency department encounters: 8,986 cases and 69,184 controls. This study assessed the effectiveness of a bivalent booster dose among immunocompetent adults during September 13th to November 18th 2022 (Omicron BA.5 sublineage predominance). Vaccine effectiveness of bivalent booster dose against emergency department or urgency care encounters was 56% (95% CI, 50% to 61%). [Tenforde MW, 2023 ]
Maeda H et al was a case-control study (test-negative design) conducted in Japan that included data from 7,931 participants: 3,055 test-positive cases and 4,876 test-negative cases. The aim was to assess vaccine effectiveness of primary and booster vaccination against symptomatic SARS-CoV-2 infections during the Omicron outbreak. Vaccine effectiveness was 67.1% (95% CI, 56.6% to 75.1%), 69.9% (95% CI, 49.3% to 82.2%) and 75.7% (95% CI, 57.7% to 86.0%) for Pfizer homologous booster, Pfizer primary schedule and Moderna booster and Moderna homologous booster, respectively. [Maeda H, 2023 ]
Vaccine efficacy and effectiveness for booster dose
Immunogenicity results
Benotmane I et al. was a non-comparative study conducted in France. The study included 159 participants (kidney transplant). This study found that a third dose of Moderna vaccine induced a serologic response in 49% of kidney transplant recipients who did not respond after 2 doses. Based on data from the French National Authority for Health that assesses the administration of a third vaccine dose in immunosuppressed patients who did not respond after two doses. [Benotmane I, 2021 ].
Hall VG et al was a phase 4, randomized, placebo-controlled trial sponsored by University Health Network, Toronto and conducted Canada May 2021 to August 2021. It was registered with trial registry number NCT04885907. The trial included organ-transplant recipients who had received two doses of mRNA-1273. The sample size was 120. The mean age of the participants was 66.6 years. The proportion of women in the mRNA-1273 group was 38.3% and in the placebo group was 30%. Participants were randomly assigned in a 1:1 ratio to receive a third dose of mRNA-1273 or a placebo. The intervention was administered as a third dose of mRNA-1273 vaccine or saline placebo 2 months after the second dose of mRNA-1273 (dosing schedule: 0, 1, and 3 months). [Hall VG, 2021 ]
Branche A et al. recruited 602 adults with primary schedules and a single homologous or heterologous boost. The participants were randomized to six Moderna vaccine arms (50µg dose): 99 received prototype Moderna vaccine, 100 received 1 dose of Beta and Omicron BA.1 bivalent vaccine, 102 received 2 doses of Beta and Omicron BA.1 bivalent vaccine, 101 received 1 dose of Delta and Omicron BA.1 bivalent vaccine, 100 received 1 dose of Omicron BA.1 monovalent vaccine and 100 received 1 dose of Omicron BA.1 Moderna bivalent vaccine. Neutralization antibody titers (ID50) were assessed for D614G, Delta, Beta, and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination. The study found that the Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218- 4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907) [Angela R Branche, 2022 ].
Anderson et al was a phase 2 randomized controlled trial conducted in the United States that included 96 participants with a primary schedule of Moderna: 48 with Monovalent prototype boost (100 mcg) of mRNA-1273, 25 with Monovalent variant boost of mRNA-1273.351 (50 mcg) and 23 with a bivalent boost of mRNA1273.351 (25 mcg ) and bivalent mRNA-1273 (25 mcg). This study assessed the immunogenicity after a third mRNA vaccination in adults who received the mRNA-1273 primary schedule approximately 9 to 10 months earlier. The booster vaccine formulations included 100 mcg of mRNA-1273, 50 mcg of mRNA1273.351 that encodes Beta variant spike protein, and a bivalent vaccine of 25 mcg each mRNA-1273 and mRNA-1273.351. The results showed that following booster vaccination, a robust response to similar titers was observed in all three groups to 614D S-2P at Day 15 [monovalent prototype 62,272 AUC (95% CI 59,973, 64,659); monovalent variant 61,373 (95% CI 58,622, 64,254); bivalent 62,025 (95% CI 59,468, 64,691). In all groups, the third dose of mRNA vaccine induced similar responses against B.1.351 [monovalent prototype 47,733 AUC (95% CI 44,932, 50,710); monovalent variant 49,768 (95% CI 46,282, 53,517); bivalent 48,126 (95% 44,728, 51,781)] that were only 20% lower than the Day 15 responses to 614D . Spike-specific CD4+ and CD8+ T cells increased to similar levels to those after the second dose. [Anderson E, 2022 ]
Chalkias S et al was an open-label, ongoing phase 2–3 study conducted in United States. The study included 819 participants with primary schedule of Moderna: 377 included in the mRNA-1273 (50 µg) booster group and 437 included in the mRNA-1273.24 (50 µg) booster omicron-containing bivalent group. This study assessed the immunogenicity, safety, and reactogenicity of bivalent booster vaccine mRNA-1273.214 as compared with the previously authorized mRNA-1273 booster vaccine in adults who had received a two-dose primary series (100 μg) and first booster dose (50 μg) of mRNA-1273. Geometric mean titers of neutralizing antibodies against Ancestral SARS-CoV-2 (D614G) were 5977.3 (95% CI 5321.9 to 6713.3) in the mRNA-1273.214 (50 µg) group and 5649.3 (95% CI 5056.8 to 6311.2) in the mRNA-1273 (50 µg) group. Adjusted geometric mean titer ratio against wild type was 1.22 (97.5% CI 1.08 to 1.37) wich met the prespecified criterion for noninferiority. Geometric mean titers of neutralizing antibodies against Omicron were 2372.4 (95% CI 2070.6 to 2718.2) in the mRNA-1273.214 (50 µg) group and 1473.5 (95% CI 1270.8 to 1708.4) in the mRNA-1273 (50 µg) group. Adjusted geometric mean titer ratio against Omicron was 1.75 (97.5% CI 1.49 to 2.04) wich met the prespecified criterion for noninferiority. The percentages of participants with a seroresponse against ancestral SARS-CoV-2 (D614G) were 100% (95% CI, 98.9 to 100) for mRNA1273.214 and 100% (95% CI, 98.6 to 100) for mRNA-1273 at 28 days after the booster doses, with an estimated difference of 0, which met the noninferiority criterion. [Chalkias S, 2022 ]
Haggenburg S et al was a cohort study conducted in Netherlands. The study included 584 immunocompromised patients with hematologic cancers. The aim of this study was to assess whether a third mRNA-1273 vaccination is associated with increased neutralizing antibody concentrations in immunocompromised patients with hematologic cancers comparable to levels obtained in healthy individuals after the standard 2-dose mRNA-1273 vaccination schedule. A third mRNA-1273 vaccination was associated with a significant increase in S1-IgG concentration. Seroconversion rates improved from 68.9% (399 of 579) to 78.8% (443 of 562), and 378 of 562 (67.3%) patients obtained S1-IgG concentration of 300 BAU/mL or greater. The rise in S1-IgG concentration after the third vaccination was most pronounced in patients with a recovering immune system, but potent responses were also observed in patients with persistent immunodeficiencies. [Haggenburg S, 2022 ]
Chalkias et al, was a phase 2/3 non-randomized trial conducted in the United States as part of a larger study registered as NCT04927065. Its aim was to evaluate the safety, reactogenicity and immunogenicity of a single booster dose of the bivalent beta-containing mRNA candidate vaccine mRNA-1273.211, in adults who received a primary schedule of mRNA-1273. The study included 300 participants who received 50 µg of mRNA-1273.211 booster, 595 participants who received 100 µg of mRNA-1273.211 booster, a historical cohort of 584 participants who received the 100 µg primary schedule and 171 participants who received a mRNA-1273 50 µg booster dose. The Geometric Mean Titers (GMT) of neutralizing antibodies against the ancestral strain were 1,996.2 (95% CI, 1,777.9–2,241.4) for the mRNA-1273.211 (50 µg) group and 4,324.7 (95% CI, 3,974.6–4,705.6) for the mRNA-1273.211 (100 µg) group. The GMT of neutralizing antibodies against the Beta variant were 953.9 (95% CI, 844.1–1,078.0) for the mRNA-1273.211 (50 µg) group and 1,574.6 (95% CI, 1,439.4–1,722.5) for the mRNA-1273.211 (100 µg) group. [Chalkias S, 2022 ]
BOOST-TX was a randomized controlled trial conducted in Austria, of a third dose of SARS-CoV-2 vaccine in kidney transplant recipients who had not developed antibodies to SARS-CoV-2 spike protein after 2 dose of an mRNA vaccine. 197 patients were analyzed, 99 received a booster of a homologous vaccine (mRNA), 98 received a heterologous vaccine (Ad26COVS1). 39% developed SARS-CoV-2 antibodies after the third vaccination. There were no statistically significant differences between groups, with an antibody response rate of 35% and 42% for the mRNA and vector vaccines, respectively. Only 22% of seroconverted patients had neutralizing antibodies. Similarly, the IGRA-assessed T-cell response was low and only 17 patients showed a positive response after the third vaccination. Receiving nontriple immunosuppression (odds ratio [OR], 3.59 (95% CI, 1.33-10.75)), longer time after kidney transplant (OR, 1.44 (95% CI, 1.15 -1.83), for doubling of years) and torque teno virus plasma (OR, 0.92 (95% CI, 0.88-0.96), for doubling of levels) were associated with response to vaccine. The third dose of an mRNA vaccine was associated with a higher frequency of local pain at the injection site compared with the vector vaccine, while systemic symptoms were comparable between groups. [Reindl-Schwaighofer R, 2021 ]
Heinzel et al was a secondary analysis of the randomized trial BOOST-TX conducted in Austria. The study enrolled 201 kidney transplant recipients without detectable SARS-CoV-2 specific antibodies following two doses of an mRNA vaccine. Participants were randomized to a third dose of the same mRNA vaccine (the mRNA group) or a dose of the vector vaccine (Janssen, Ad26COVS1). A total of 169 patients were available for the 3-month follow-up. Overall, seroconversion at 3 months was similar between both groups (45% vs. 50% for mRNA and the vector group, respectively; p = 0.539). However, when applying higher cut-off levels, a significantly larger number of individuals in the vector group reached antibody levels > 141 and > 264 BAU/ml at the 3-month follow-up (141 BAU/ml: 4% vs. 15%, p = 0.009 and 264 BAU/ml: 1% vs. 10%, p = 0.018 for mRNA vs. the vector vaccine group, respectively). [Heinzel A, 2022 ]
Effectiveness results
mBoost was an open-label trial conducted in Qatar. The study included 2,232,224 vaccinated persons with at least two doses. This study compared protection afforded by booster doses of Moderna vaccine, compared to the primary series of only two doses in Qatar. Study results showed that there were fewer cases of severe COVID-19 in booster-dose cohorts than in primary-series cohorts, but cases of severe COVID-19 were rare in all cohorts. Booster effectiveness relative to primary series was 50.8% (95% CI: 43.4-57.3%)[Laith J Abu-Raddad, 2022 ].
Accorsi EK et al included 23 391 cases and 46 764 controls (3 doses= 12 476; 2 doses=19839; Unvaccinated= 17 177). Data were collected ≥14 days after dose 3 and ≥6 months between doses 2 and 3. The study showed that receiving three doses of Moderna COVID-19 vaccine compared to not receiving any or receiving only two doses, was associated with protection against both the Omicron and Delta. Comparison of 3 Doses vs Unvaccinated showed for Omicron variant OR 0.28 (95% CI 0.26 to 0.31) and for Delta variant OR 0.045 (95% CI 0.038 to 0.053). Comparison of 3 Doses vs 2 Doses showed for Omicron variant OR 0.31 (95% CI 0.28 to 0.34) and for Delta variant OR 0.13 (95% CI 0.11 to 0.15)[Accorsi EK, 2022 ].
McConeghy KW et al. included 14,259 participants (8,538 control and 5,721 boosted residents). Data were collected 42 days after the booster dose. The combined results showed that a Pfizer or Moderna COVID-19 vaccine booster dose reduced infections by 50.4% (95% CI 29.4% to 64.7%) in nursing home residents and 58.2% (95% CI 32.3% to 77.8%) in veterans residing in community living centers. Nursing homes residents with booster dose also had a 97.3% (95% CI 86.9% to 100.0%) reduction in SARS-CoV-2 associated death, but too few events for comparison in veterans residing in community living centers [Kevin W McConeghy, 2022 ].
Buchan S et al. included 134,435 tests (Omicron-positive cases=16,087; Delta-positive cases= 4,261 test-negative controls= 114,087). Data were collected from December 6 to 26, 2021. The study showed that 2 doses of COVID-19 vaccines only offer modest and short-term protection against symptomatic Omicron infection. A third dose improves protection against symptomatic infection and provides excellent protection against severe outcomes for Delta and Omicron variants. Vaccine efficacy against Delta variant was 97% (95% CI 95 to 98) and 65% (95% CI 55 to 72) for Omicron in symptomatic infection 7 days after a third dose [Buchan, S. A., 2022 ].
Johnson AG et al was a cohort study conducted in the United States. The study enrolled 6,812,040 COVID-19 cases in unvaccinated persons and 2,866,517 cases in fully vaccinated persons. Data were collected between April 4, 2021, and December 25, 2021. During periods of Delta and Omicron variant emergence. The protection against infection during the Delta predominant period (October-November) was higher among booster recipients, especially among persons over 50 years of age. The average weekly IRR was 4.6 (95% CI 4.2 to 5.1) for the group without a booster and IRR 17.4 (95% CI 14.5 to 21.1) for the booster group.[Johnson AG, 2022 ]
The VISION Network study included 222,772 encounters from 383 emergency departments (ED) and urgent care (UC) and 87,904 hospitalizations from 259 hospitals. Data were collected during periods of Delta and Omicron variant predominance between august 2021to and January 2022. Based on all results combined, during the Delta-predominant period, vaccine effectiveness against Lab-confirmed COVID-19 was significantly lower among patients who received the second dose ≥180 days earlier (76%; 95% CI 75 to 77) than among those who received the third dose (94%; 95% CI 93 to 94). In the omicron-predominant period, vaccine effectiveness against the same outcome was significantly lower among those who received the second dose ≥180 days earlier (38%; 95% CI 32 to 43) than those who received the third dose (82%; 95% CI 79 to 84). In addition, vaccine effectiveness against hospitalization was 90% (95% CI 89 to 90) in those who received the second dose <180 days earlier, 81% (95% CI 80 to 82) in those who received the second dose ≥180 days earlier and 94% (95% CI 93 to 95) in those who received the third dose, during Delta period. In the Omicron period, vaccine effectiveness against hospitalization was 81% (95% CI 65 to 90) in those who received the second dose <180 days earlier, 57% (95% CI 39 to 70) in those who received the second dose ≥180 days earlier and 90% (95% CI 80 to 94) in those who received a third dose [Thompson MG, 2022 ].
Chemaitelly H et al.was a case-control study conducted in Qatar based on data from a test-negative design study that seeks to assess the duration of protection of Pfizer-BioNTech after the second dose and after the third/booster dose against symptomatic Omicron infection and against COVID-19 hospitalization and death, between December 23, 2021, and February 2, 2022. Vaccine effectiveness was 53.1% (95% CI 40.7 to 62.8) 2 to 3 weeks after receiving the booster dose. [Hiam Chemaitelly, 2022 ].
Draws PE et al. was a case-control study conducted in the United States. The study enrolled 4,547,945 participantes: 1,732,112 were fully vaccinated with Pfizer–BioNTech and 1,066,645 were fully vaccinated with Moderna. A Pfizer–BioNTech booster was administered to 609,153 individuals and a Moderna booster was administered to 395,634 individuals The study is based on statewide COVID-19 vaccination data from the Minnesota Immunization Information Connection (MIIC) linked via a privacy-preserving record linkage process with distributed electronic health record (EHR) data from the 11 largest health systems in Minnesota. The main results showed that vaccine effectiveness after 26 weeks from the second dose was 65% (95% CI 65 to 66) for the Moderna COVID-19 Vaccine. [Drawz PE, 2022 ]
Shrestha NK et al. was a cohort study conducted in the United States, Based on data from the Cleveland Clinic Health System in Ohio, United States, all employees vaccinated (with both Pfizer-BioNTech and Moderna) or who have a history of prior COVID-19 infection until November 26, 2021 were included, with a follow-up period of 90 days. Vaccine effectiveness during the Omicron variant boost was 57% (95% CI: 54% to 59%) for the full schedule and a boost with mRNA [Nabin K Shrestha, 2022 ] vaccines.
Tan SHX et al. was a comparative cohort study conducted in China. Rates and severity of SARS-CoV-2 infections between September 15 and October 31, 2021, among those eligible to receive vaccine boosters between September 15 and October 15, 2021, were analyzed based on official data reported to the Singapore Ministry of Health. The adjusted incidence rate ratios (3 doses of mRNA-1273) for individuals with PCR–confirmed infections was 0.198 (95% CI 0.144 to 0.271) [Tan SHX, 2022 ].
Kislaya I et al. was a case-control study conducted in Portugal, the study enrolled 15,001 participants, 3.737 were eligible for a booster dose of Pfizer-BioNTech. Based on data from RT-PCR SARS-CoV-2 positive cases were notified in the mandatory National Epidemiological Surveillance Information System (SINAVE) in Portugal. The booster effectiveness against Delta variant was 94% (95% CI: 93.4 to 94.6) and for Omicron variant the booster effectiveness was 68.8% (95% CI: 46.4 to 81.7) [Irina Kislaya, 2022 ].
Abu-Raddad LJ et al. was a study conducted in Qatar including data from 2,239,193 vaccinated individuals: 1,299,010 with Pfizer-BioNTech and 890,619 with Moderna, the study also included matched unvaccinated controls. The study analyzed information from national, federated databases regarding Covid-19 vaccination, laboratory testing, hospitalization, and death from December 19, 2021, through January 26, 2022. The vaccine effectiveness against the Omicron variant of the booster dose compared to the two-dose regimen was 47.3% (95% CI 40.7 to 53.3) for symptomatic infection. [Abu-Raddad LJ, 2022 ].
Andrews N et al. was a case-control study conducted in England. The study enrolled 2,663,549 vaccinated participants: 204,154 cases for Delta variant, 886,774 cases for Omicron variant and 1,572, 621 test-negative controls. The study analyzed information from national databases, Pillar 1, Pillar 2, NIMS and NHS regarding Covid-19 vaccination, testing, and variants from November 25, 2021, through January 12, 2022. Moderna effectiveness against Delta variant for symptomatic infection was 57.4% (95% CI 52.6 to 61.8) 4 weeks after the first dose, 80.4% (95% CI 67.3 to 88.2) 25 weeks after the second dose, 94.7% (95% CI 89.3 to 97.3) 2-4 weeks after a Pfizer-BioNTech booster and 96.4% (95% CI 91.4 to 98.5) 2-4 weeks after Moderna booster [Andrews N, 2022 ].
Ng OT et al was cohort study conducted in Singapore. The study included 2,441,581 eligible individuals. It was based on data from the Singapore Ministry of Health’s (MOH) official COVID-19 database, including individuals who had received 2 or 3 doses of mRNA vaccines (by Pfizer-BioNTech or Moderna) or inactivated vaccines (by Sinovac or Sinopharm) and notified infections from December 27th 2021 to March 10th 2022. Effectiveness of booster dose against COVID-19 Infeccion was 35.6% (95%CI 32.8-38.3) and 97.5% (95% CI 89.7 - 99.4) against Severe COVID Infeccion. [Ng OT, 2022 ]
Lin DY et al, was a comparative cohort study conducted in the USA. The study included 10,600,823 individuals, among which were 2,771,364 cases of COVID-19. IBased on data from the North Carolina COVID-19 Surveillance System and the Covid-19 Vaccine Management System, including data from residents of North Carolina from December 11, 2020, to September 8, 2021. Vaccine effectiveness of Moderna homologous booster was 62.1% (95%CI 60.7 to 63.5) after 1 month. [Lin DY, 2022 ].
Risk M et al was a retrospective cohort study conducted in the United States including 168,414 participants: 133,238 vaccinated with mRNA vaccines and 35,176 unvaccinated. Based on data from the Michigan Medicine health-care system, the Michigan State Registry and chart-reviewed COVID-19 hospitalization data. Including patients 18 years old and above, who received mRNA based COVID-19 vaccines. During the Omicron dominant period December 2021 to March 2022. The effectiveness of the Moderna vaccine during the Omicron period was 16% (95%CI 5 to 26) for two doses and 57% (95%CI 51 to 62) for three doses. [Risk M, 2022 ]
Monge S et al, was a nationwide Cohort study conducted in Spain. This study included 7,036,433 participants older than 40 years: 3,111,159 in the booster group and 3,111,159 in the no booster group. The aim of this study was to estimate the effectiveness of mRNA-based vaccine boosters against infection during the period of the predominance of the omicron variant in Spain. Vaccine effectiveness with Moderna booster and AstraZeneca, JAnssen, Moderna or Pfizer primary schedule was 52,5% (95% CI, 51,3–53,7). Vaccine effectiveness of Moderna primary schedule and ARNm booster was 55.3% (95% CI, 52.3–58.2) (Moderna or Pfizer booster dose). [Monge S, 2022 ]
Ferdinands JM et al was a test-negative case-control study conducted in United States. The study included data from 259,006 hospital admissions: 213,103 with SARS-CoV-2 negative test and 45,903 with SARS-CoV-2 positive test. The main outcome was waning of vaccine effectiveness with BNT162b2 or mRNA-1273 vaccine during the omicron and delta periods. Vaccine effectiveness (VE) against COVID-19-associated hospitalizations during the Omicron-predominant period for Moderna vaccine was 87% (95% CI, 75-93) (less than two months after the second dose) and 91% (95% CI, 89-92) with the third booster dose. Vaccine effectiveness (VE) against COVID-19-associated hospitalizations during the Delta-predominant period for Moderna vaccine was 98% (95% CI, 97-99) (less than two months after the second dose) and 97% (95% CI, 96-98) with the third booster dose.[Ferdinands JM, 2022 ]
Grewal R et al. was a case-control study (test negative design) conducted in the United States. The aim of this study was to estimate the marginal effectiveness of a fourth versus third dose and the vaccine effectiveness of mRNA COVID-19 vaccines BNT162b2 and mRNA-1273 against any infection, symptomatic infection, and severe outcomes (hospital admission or death) related to the Omicron variant. Vaccine effectiveness of three doses of Moderna vaccine against the Omicron variant to any infection was 44% (95% CI, 38% to 49%), against symptomatic infection was 61% (95% CI, 50% to 69%) and against severe outcomes 81% (95% CI, 74% to 86%).[Grewal R, 2022 ].
Mehta HB et al was a retrospective cohort study conducted in the United States that included 3,940,475 boosted individuals and 3,940,475 controls. Based on data from Medicare beneficiaries who received 2 doses of Pfizer or 2 doses of Moderna vaccine as the primary vaccination series from December 11th 2020 to December 31st 2021. The vaccine effectiveness against hospitalization of an mRNA booster dose after a mRNA primary schedule was 81% (95% CI, 80% to 82%). [Mehta HB, 2022 ]
Hung FT et al fue un estudio de casos y controles conducido en Estados Unidos que incluyó 123.236 participantes, 30.809 casos y 92.427 controles. Basado en datos de KPSC, registros electrónicos, el registro de inmunización de California (CAIR) y el servicio Care Everywhere, durante el período de predominancia de Ómicron (entre enero y junio de 2022). El estudio evaluó la efectividad de una tercera y cuarta dosis de Moderna. La efectividad ajustada contra la infección 14-30 días después de la tercera dosis fue de 72,6% (IC 95%, -54,7% a 96,6%) contra BA.4 y 90,6% (IC 95%, 30,6% a 98,7%) contra BA.5. Luego de la cuarta dosis la efectividad de la vacuna fue de 75,7% (IC 95%, 44,7% a 91%) contra BA.4 y 30,8% (IC 95%, -9,2% a 56,5%) contra BA.5. La efectividad ajustada contra la hospitalización luego de la tercera dosis fue de 72,4% (IC 95%, 23,9% a 90%) contra BA.4/BA.5 y luego de la cuarta dosis fue de 88,5% (IC 95%, 51,8% a 97,2%). [Hung Fu Tseng, 2022 ]
Baum U et al was a cohort study conducted in Finland including 896,220 participants aged 70 years and over. The study was based on a nationwide register-based cohort, between December 27th 2020 and March 31st 2022. Vaccine effectiveness of the booster against hospital admission was 97% (95% CI, 93% to 98%). [Baum U, 2022 ]
Grewal R was a case-control study conducted in Canada that included data from 3,736 Omicron positive cases and 77,695 SARS-CoV-2 negative controls. The aim was to estimate the effectiveness of a fourth dose of an mRNA vaccine against Omicron infections and severe outcomes over time. Vaccine effectiveness (VE) against symptomatic infection was 51% (95% CI, 42% to 60%), and 69% (95% CI, 61% to 75%) after the third and fourth doses, respectively. VE against severe outcomes was 77% (95% CI, 68% to 83%), and 79% (95% CI, 71% to 84%) after the third and fourth doses, respectively. [Grewal R, 2022 ]
Yuanyuan F et al. was an observational study to analyze vaccination status and SARS-CoV-2 infection data from more than 10.4 million participants in the national COVID Cohort Collaborative during an 18-month-period (December 2020 to June 2022) in the United States. Vaccine Effectiveness for a Moderna homologous booster dose was 47.59% (95% CI, 46.72% to 48.45%) against COVID-19 infection, and 81.09% (95% CI, 79.17% to 82.85%) against COVID-19-related death. [Yuanyuan Fu, 2022 ]
Huiberts A et al. was a prospective cohort study conducted in Netherlands that included 27,646 participants from the Omicron period: 3,802 received primary vaccination schedule, 23,352 received first booster dose and 492 were unvaccinated. The primary outcome was contracting SARS-CoV-2 between July 12th 2021 and June 6th 2022. Vaccine effectiveness (VE) against contracting COVID-19 during the Omicron BA.1-2 period was 15.8% (95% CI, -26.3% to 43.9%), 68.3% (95% CI, 63.1% to 72.8%) and 67.6% (95% CI, 60.1% to 73.7%) for Moderna primary schedule, mRNA primary schedule with Moderna booster and AstraZeneca primary schedule with Moderna booster, respectively. VE against contracting COVID-19 during the Delta period was 100% (95% CI, 0% to 100%) and 100% (95% CI, 0% to 100%) for Moderna primary schedule and mRNA primary schedule with Moderna booster, respectively. [Anne J. Huiberts, 2023 ]
Tseng HF et al was a test negative case control study conducted in United States that included data from 123,236 participants: 30,809 with a SARS-CoV-2 positive test and 92,427 with SARS-CoV-2 negative test. This study assessed vaccine effectiveness against infection and hospitalization with Omicron sub-variants. Adjusted vaccine effectiveness against hospitalization for Omicron sub-variants for 3 doses was 97.5% (95% CI, 96.3% to 98.3%), 82% (95% CI, 64.5% to 90.8%) and 72.4% (95% CI, 23.9% to 90.0%) for BA.1, BA.2 and BA.4/BA.5 sub-variants, respectively. Adjusted vaccine effectiveness against hospitalization for Omicron sub-variants for 4 doses was 96.4% (95% CI, 88.4% to 98.9%) and 88.5% (95% CI, 51.8% to 97.2%) for BA.2 and BA.4/BA.5 sub-variants, respectively. [Tseng HF, 2023 ]
Weng C et al was a comparative study conducted in United States that included 38,602 participants: 22,247 with at least one SARS-CoV-2 PCR test. The aim was to assess mRNA vaccine effectiveness (VE) in preventing SARS-CoV-2 infections. Adjusted VE of 2 doses of Moderna was 97.5% (95% CI, 82.5% to 99.7%). Adjusted VE against Omicron (2 doses of Moderna) was 25.6% (95% CI, 10.7% to 39.0%). Adjusted VE against Omicron (3 doses of Moderna) was 71.2% (95% CI, 24.0% to 90.8%). [Weng CH, 2023 ]
Maeda H et al was a case-control study (test-negative design) conducted in Japan that included data from 7,931 participants: 3,055 test-positive cases and 4,876 test-negative cases. The aim was to assess vaccine effectiveness of primary and booster vaccination against symptomatic SARS-CoV-2 infections during the Omicron outbreak. Vaccine effectiveness was 67.1% (95% CI, 56.6% to 75.1%), 69.9% (95% CI, 49.3% to 82.2%) and 75.7% (95% CI, 57.7% to 86.0%) for Pfizer homologous booster, Pfizer primary schedule and Moderna booster and Moderna homologous booster, respectively. [Maeda H, 2023 ]
Vaccine efficacy and effectiveness for heterologous schedule
Immunogenicity results
Macchia et al, was a randomized noninferiority clinical trial conducted in Argentina. The study compared the immune response generated by the homologous Sputnik V regimen to heterologous Sputnik V vaccine regimens with Moderna, Sinopharm BIBP, or AstraZeneca vaccines. The study showed that all but the Moderna regimen were statistically inferior to the standard Sputnik V regimen (rAd26/rAd5). The Moderna regimen showed a 3.53-fold increase in antibody concentrations compared to the standard Sputnik V regimen. [Macchia A, 2022 ]
ARNCOMBI was a randomized controlled trial conducted in France. The study included 414 individuals who received a first dose mRNA vaccine and a second dose of Pfizer-BioNTech or Moderna after 28 days. The primary outcome was to compare the immune response generated by the homologous Pfizer-BioNTech schedule to Pfizer-BioNtech/Moderna schedule. The study showed that the GMT antibodies were higher with the heterologous schedule compared to the Pfizer-BioNTech homologous regimen. [Janssen C, 2022 ]
Pascuale CA et al was a comparative cohort sutdy conducted in Argentina. The study enrolled 1,314 participants who had received the first dose of Sputnik V C1 (n = 669), AstraZeneca (n = 448), or BBIBPCorV (n = 197): 148 with Moderna second dose and Sputnik first dose, 67 Moderna second dose and AstraZeneca first dose, and 42 Moderna second dose and BBIBPCorV first dose. The study assessed the immunogenicity and reactogenicity by comparing homologous vaccination programs using either Sputnik V, ChAdOx1-S, or BBIBP-CorV with different heterologous schemes to define strategies to accelerate vaccination plans. A second dose of mRNA-1273 induced the highest antibody response in all cohorts. The levels of IgG anti-spike antibodies and the serum neutralizing capacity of the heterologous combinations with mRNA-1273 in all arms were similar to those obtained with the homologous two-dose schedule with mRNA1273, used as the reference. In all three cohorts, heterologous vaccination with mRNA-1273 resulted in a significant (p < 0.01) increase in the serum neutralizing titers compared with the homologous schemes. [Pascuale CA, 2022 ]
RECOVAC was a randomized trial conducted in the Netherlands that enrolled 333 kidney transplant recipients (KTR) who did not seroconvert after an initial mRNA vaccine schedule: 230 KTRs were randomly assigned in a 1:1:1 manner to receive 100 μg mRNA-1273, 2 × 100 μg mRNA-1273, or Ad26.COV2-S vaccination. In addition, 103 KTRs receiving 100 μg mRNA-1273, were randomly assigned 1:1 to continue (mycophenolate mofetil+) or discontinue (mycophenolate mofetil-) mycophenolate mofetil or mycophenolic acid treatment for 2 weeks. The primary outcome was the percentage of participants with a spike protein (S1)-specific IgG concentration of at least 10 binding antibody units per mL at 28 days after vaccination. The seroreponse rates were 68% (95% CI, 56% to 79%) for the 2 × mRNA-1273 group, 63% (95% CI, 51% to 74%) for the Ad26.COV2-S group and 68% (95% CI, 57% to 79%) for the single mRNA-1273 group. The seroresponse rate in mycophenolate mofetil- was 80% (95% CI, 66% to 91%) and 67% (95% CI, 52% to 80%) in mycophenolate mofetil+. [Kho MML, 2022 ]
Effectiveness results
Chung et al. conducted a case-control study with a test-negative design to estimate vaccine effectiveness (VE) against SARS-CoV-2 infection after the primary schedule of any combination of BNT162b2, mRNA-1273, and ChAdOx1 between January 11th and November 21st 2021 in Ontario, Canada. They included 261,360 test-positive cases (of any SARS-CoV-2 lineage) and 2,783,699 individuals as test-negative controls. VE for ChAdOx1/mRNA-1273 7-59 days after second dose was 91% (95% CI, 89% to 93%) against any infection, 96% (95% CI, 93% to 97%) against symptomatic infection and 99% (95% CI, 95% to 100%) against severe outcomes. VE for ChAdOx1/mRNA-1273 60-119 days after second dose was 87% (95% CI, 85% to 89%) against any infection, 93% (95% CI, 91% to 94%) against symptomatic infection and 99% (95% CI, 98% to 100%) against severe outcomes. [Chung H, 2022 ]
Castelli JM et al was a test-negative case-control study conducted in Argentina that included 844,460 children and adolescents without previous SARS-CoV-2 infection eligible to receive a primary vaccination schedule. The aim was to assess the effectiveness of different combinations of mRNA vaccines in children and adolescents. Vaccine effectiveness for the Pfizer/Moderna heterologous schedule was 88.9% (95% CI, 66.1% to 96.4%) during the Delta predominance period, and 40.6% (95% CI, 29.4 to 50.0) during the Omicron predominance period. [Castelli JM, 2022 ]
Yuanyuan fu et al. was an observational study to analyzed vaccination status and SARS-CoV-2 infection data from more tha 10.4 million participants in the national COVID Cohort Collaborative (N3C) during an 18-month-period (December 2020 to June 2022) in the United States. Vaccine Effectiveness against COVID-19 infection was 35.17% (95% CI, 31.71% to 38.50%) for the Moderna/Pfizer schedule. [Yuanyuan Fu, 2022 ]
Vaccine efficacy and effectiveness for heterologous booster schedule
Immunogenicity results
Bonelli M et al. was a clinical trial that evaluated the efficacy and safety of a booster dose in patients in whom serconversion did not occur after the second dose. The additional booster dose was delivered with the AstraZeneca or mRNA vaccines against COVID-19. Efficacy was measured by the difference in the SARS-CoV-2 antibody seroconversion rate between patients vaccinated with the AstraZeneca vaccine (heterologous) and the mRNA vaccines (homologous) at the fourth week. The results demonstrated that seroconversion rates at week four were comparable between patients who received the AstraZenaca vaccine (6/27 patients, 22%) versus the mRNA vaccines (9/28, 32%) (p = 0, 6). Overall, 27% of the patients seroconverted; furthermore, no serious adverse events related to immunization were observed. [Michael Bonelli, 2021 ].
COV-BOOST was a clinical trial that evaluated the immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer–BioNtech, hearafter referred to as BNT). Efficacy was measured by neutralizing antibody titers at 28 days post-boost dose. The results demonstrated that all study vaccines boosted antibody and neutralising responses after AstraZeneca/AstraZeneca initial course and all except one after Pfizer/Pfizer, with no safety concerns [Munro, Alasdair P S, 2021 ].
SWITCH was a randomized trial sponsored by Erasmus Medical Center and conducted in the Netherlands between June 2021 to September 2022. Immunogenicity was assessed 28 days after homologous or heterologous booster vaccination. Results showed that the Janssen COVID-19 vaccine and mRNA boosters vaccines were immunogenic in health care workers who had received a priming dose of the Janssen vaccine. In addition, the Moderna and Pfizer COVID-19 boosters vaccines led to higher T-cell responses than the Janssen COVID-19 booster vaccine. The immune response was 91.7% with the Moderna booster and 91.5% with the Pfizer booster; both performed better than the homologous booster (response, 72.7%) [Sablerolles RSG, 2022 ].
SWITCH was a randomized trial sponsored by Erasmus Medical Center and conducted in the Netherlands between June 2021 to September 2022. Immunogenicity was assessed 28 days after homologous or heterologous booster vaccination. Results showed that the Janssen COVID-19 vaccine and mRNA boosters vaccines were immunogenic in health care workers who had received a priming dose of the Janssen vaccine. In addition, the Moderna and Pfizer COVID-19 boosters vaccines led to higher T-cell responses than the Janssen COVID-19 booster vaccine. The immune response was 91.7% with the Moderna booster and 91.5% with the Pfizer booster; both performed better than the homologous booster (response, 72.7%) [Sablerolles RSG, 2022 ].
Kanokudom S et al. recruited 222 adults with a complete CoronaVac regimen who received a booster dose of 15μg Pfizer-BioNTech vaccine (n=59), and 50μg Moderna vaccine (n=51), standard Pfizer-BioNTech vaccine (n=54)or standard Moderna vaccine (n=58). The study found no significant differences in binding antibody levels between standard and reduced doses. 28 days after the booster dose binding antibody levels were 41,171 U/mL and 51,979 U/mL for the reduced and standard Moderna vaccines. Boosting elicited an increase in median IFN-γ CD4+ T cell and CD4+ CD8+ T cell counts; there were no differences in T cell counts between the standard and reduced dose groups. [Kanokudom S, 2022 ].
Poh X et al. is an ongoing phase 4 randomized clinical trial conducted in Singapore, assessing the humoral response elicited by homologous and heterologous booster vaccination regimens based on a primary regimen with Pfizer-BioNTech. Interim results of two groups have been published. The study recruited 100 participants who either received a Pfizer-BioNTech (n=51) booster or a Moderna booster (n=49). Results show a booster dose increases antibody titers in all participants by 35- to 49- fold on day 7, with only a modest increase by day 17. Antibody titers were higher in the Moderna group, particularly in the ≥60 years age subgroup. On day 28 antibody titer reached 29.751 (IC 95%: 25.281-35.011) UI/mL for the Moderna group and 22 382 (IC del 95 %: 18 210-27 517) UI/mL for the Pfizer-BioNTech group. Neutralization against the Omicron variant was higher in the Moderna group at day 7 but similar at day 28 [Xuan Ying Poh, 2022 ].
Chuang et al. was a randomized controlled study made in Taiwan. It included data from samples of 340 health care workers (HCW) with prior Oxford-AstraZeneca homologous vaccination and that received one of the four vaccines as booster doses: Pfizer–BioNTech, half-dose Moderna, full dose Moderna or MVC-COV1901. The primary outcomes were humoral and cellular immunogenicity and the secondary outcomes safety and reactogenicity 28 days post-booster. The study found that, compared with pre-boost, all study vaccines elicited significantly higher anti-spike IgG at 28 days post-boost (P < 0.0001). The mRNA vaccines had more reactogenicity than the protein vaccine [Chih-Hsien Chuang, 2022 ].
COV-BOOST was a phase 2 randomized clinical trial conducted in the United Kingdom. This study enrolled 166 participants who had received Pfizer-BioNTech as their third dose and randomly assigned them to receive a fourth dose of either Pfizer-BioNTech (30 µg in 0.30 mL; full dose) or Moderna (50 µg in 0.25 mL; half dose). It was compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. The results showed a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25,317 ELU/mL, 95% CI 20,996–30,528) to 14 days after a fourth dose of Moderna (54 936 ELU/mL, 46,826–64,452), with a geometric mean fold change of 2,19 (1,90–2,52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12,19 (95% CI 10,37–14,32) and 15,90 (12,92–19,58) in the Pfizer–BioNTech and Moderna groups, respectively. T-cell responses were also boosted after the fourth dose (the fold changes for the wild-type variant from before to after the fourth dose were 7,32 [95% CI 3,24–16,54] in the Pfizer–BioNTech group and 6,22 [3,90–9,92] in the Moderna group). [Munro APS, 2022 ]
Suntronwong N et al. was a cohort study conducted in Thailand. One hundred and sixty-seven participants primed with heterologous CoronaVac/Oxford-AstraZeneca vaccination were enrolled to receive a booster dose of Oxford-AstraZeneca (n= 60), Pfizer-BioNTech (n= 55) of Moderna (n= 52) vaccines. This study assessed the capability of the booster vaccination to induce an increase in neutralizing antibodies and T-cell responses against SARS-CoV-2, Omicron (BA.1 and BA.2), and Delta variants. The study showed that, following the booster dose, the anti-RBD IgG significantly increased and peaked at day 14 for all vaccines (p< 0.001). Comparing pre and post-boost, the Moderna vaccine induced an anti-RBD IgG 23-fold increase (126.9 vs. 2921 BAU/ml) and showed a higher level than the other vaccine groups. 90-97% of individuals boosted with Pfizer and Moderna induced IFN-γ responses at 14 days. [Suntronwong N, 2022 ]
BOOST-TX was a randomized controlled trial conducted in Austria, assessing a third vaccine dose against SARS-CoV-2 in kidney transplant recipients who had not developed SARS-CoV-2 spike protein antibodies after 2 doses of an mRNA vaccine. 197 patients were analyzed, 99 received an homologous booster (mRNA) vaccine, 98 received an heterologous (Ad26COVS1) vaccine. 39% developed SARS-CoV-2 antibodies after the third vaccine. There was no statistically significant difference between groups, with an antibody response rate of 35% and 42% for the mRNA and vector vaccines, respectively. Only 22% of seroconverted patients had neutralizing antibodies. Similarly, T-cell response assessed by IGRA was low with only 17 patients showing a positive response after the third vaccination. Associated with vaccine response were cases receiving nontriple immunosuppression (Odds Ratio [OR] 3.59 (95% CI, 1.33-10.75)), longer time after kidney transplant (OR 1.44 (95% CI, 1.15-1.83), per doubling of years), and torque teno virus plasma levels (OR, 0.92 (95% CI, 0.88-0.96), per doubling of levels). The third dose of an mRNA vaccine was associated with a higher frequency of local pain at the injection site compared with the vector vaccine, while systemic symptoms were comparable between groups. [Reindl-Schwaighofer R, 2021 ]
Bonelli et al was a randomized controlled trial in Austria that assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 or mRNA-1273, to receive a third dose, either using the same mRNA (28/30) or the vector vaccine ChAdOx1 nCoV-19 (27/30). Seroconversion rates at week 4 were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccines (p=0.6). Overall, 27% of patients seroconverted; specific T cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. 3/37 (8%) of patients without and 12/18 (67%) of the patients with detectable peripheral B cells seroconverted. No serious adverse events, related to immunization, were observed. [Bonelli M, 2022 ]
mRNA-1273-P205 was an open-label, phase 2/3 study conducted in the United States that included 819 participants with a primary schedule of Moderna: 377 included in the mRNA-1273 (50 µg) booster group, and 437 included in the mRNA-1273.24 (50 µg) Omicron BA,.1-containing bivalent vaccine group. Geometric mean titers (GMT) of neutralizing antibodies against ancestral SARS-CoV-2 (D614G) were 5977.3 (95% CI, 5321.9-6713.3) in the mRNA-1273.214 (50 µg) group and 5649.3 (95% CI, 5056.8-6311.2) in the mRNA-1273 (50 µg) group. The adjusted GMT ratio against the wild type was 1.22 (97.5% CI, 1.08-1.37) which met the prespecified criterion for noninferiority. GMT of neutralizing antibodies against Omicron were 2372.4 (95% CI, 2070.6-2718.2) in the mRNA-1273.214 (50 µg) group and 1473.5 (95% CI, 1270.8.1708.4) in the mRNA-1273 (50 µg) group. Adjusted GMT against Omicron was 1.75 (97.5% CI, 1.49-2.04) which met the prespecified criterion for noninferiority. The percentages of participants with a seroresponse against ancestral SARS-CoV-2 (D614G) were 100% (95% CI, 98.9% to 100%) for mRNA1273.214 and 100% (95% CI, 98.6% to 100%) for mRNA-1273 at 28 days after the booster doses, with an estimated difference of 0, which met the noninferiority criterion. [Chalkias S, 2022 ]
mRNA-1273-P205 was an open-label, phase 2/3 study conducted in the United States that included 887 participants with a primary schedule of Moderna and a first homologous booster: 176 received a second booster dose of mRNA-1273 (50 µg) and 511 received a second booster dose of the Omicron BA.4/BA.5-containing mRNA-1273.222 (50 µg) vaccine. Geometric mean titers (GMT) of neutralizing antibodies against the ancestral SARS-CoV-2 (D614G) strain were 7322.4 (95% CI, 6386.2-8395.7), and 5651.4 (95% CI, 5055.7-6317.3) for mRNA-1273.222 (50 µg) and mRNA-1273 (50 µg), respectively. GMT of neutralizing antibodies against Omicron were 2324.6 (95% CI, 1921.2-2812.7), and 488.5 (95% CI, 427.4-558.4) for mRNA-1273.222 (50 µg), and mRNA-1273 (50 µg), respectively. [Spyros Chalkias, 2022 ]
SWITCH ON was an open-label randomized trial conducted in the Netherlands that included 187 healthcare workers: 42 with Ad26.COV2.S primary schedule and BNT162b2 Omicron BA.1 booster, 45 with Ad26.COV2.S primary schedule and mRNA-1273.214 Omicron BA.1 booster, 44 with mRNA-based primary schedule and BNT162b2 Omicron BA.1 booster and 56 mRNA-based primary schedules and mRNA-1273.214 Omicron BA.1 booster. The aim was to assess the fold change in S1-specific IgG antibodies before and 28 days after booster vaccination. Fold change of S1-specific binding antibody levels between baseline and 28 days after bivalent booster vaccination was 2.9, 3.6, 4.3, and 3.5-fold for participants with Ad26.COV2.S+BNT162b2 Omicron BA.1 booster, mRNA-based primary schedule+BNT162b2 Omicron BA.1 booster, Ad26.COV2.S+mRNA-1273.214 Omicron BA.1 booster, and mRNA-based primary schedule+mRNA-1273.214 Omicron BA.1 booster, respectively. [Ngoc Tan, 2022 ]
Prasert Assantachai et al was a randomized controlled trial conducted in Thailand that included 210 participants aged ≥65 years with AstraZeneca primary schedule: 35 received intradermal mRNA-1273, 35 intramuscular mRNA-1273, 70 intradermal BNT162b2, and 70 intramuscular BNT162b2. The group that reported the highest geometric mean titers against the ancestral strain and Omicron BA.1 variant was the group that received the intramuscular mRNA-1273 vaccine (GMT 1,717.9 and 617), followed by the group that received the intradermal mRNA-1273 vaccine (GMT 1,212 and 318), the group that received the intramuscular BNT162b2 vaccine (GMT 713 and 230 and the group that received the intradermal BNT162b2 vaccine (GMT 587 and 148), respectively. [Prasert Assantachai, 2022 ].
Lee I et al was a phase 3 randomized trial conducted in the United Kingdom that assessed the immunogenicity and safety of 50 µg doses of Omicron-BA.1- monovalent mRNA-1273.529 and bivalent mRNA-1273.214 booster vaccines compared with 50 µg mRNA-1273. Neutralizing antibody geometric mean concentrations against Omicron BA.1 were 537.7 (95% CI, 478.2−604.6) for mRNA-1273.529 booster and 307.4 (95% CI, 279.5−338.2) for mRNA-1273 booster. [Lee, I. T., 2023 ]
Jäger M et al was a comparative cohort study conducted in Austria that included 137 participants, of which 79 were vaccinated with AstraZeneca primary schedule and mRNA vaccine booster, and 40 with 3 doses of mRNA vaccine. The aim was to assess humoral and cellular response. Median IgG titers were 1655.0 (95% CI, 1163.0-1901.0), 2673.0 (95% CI, 2189.0-3517.0) and 2891.0 (95% CI, 1582.0-4458.0) for particpants with 2 AstraZeneca doses and Pfizer booster group, 2 AstraZeneca doses and Moderna booster and 3 Pfizer doses, respectively. [Jäger M, 2023 ]
2019nCoV-307 was a phase 3 randomized trial conducted in United States that included data from 911 participants boosted with three different manufacturing lots of NVXCoV2373 COVID-19 vaccines: 298 from group 1, 303 from group 2 and 304 from group 3. This study assessed whether NVX-CoV2373 would induce similar responses when used as a heterologous or homologous booster. Geometric mean fold rise (day 29 vs baseline) was 4.0 (95% CI, 1.0-16.0) for homologous booster. Geometric mean fold rise (day 29 vs baseline) was 2.7 (95% CI, 2.3-3.2), 2.4 (95% CI, 1.9-2.9) and 2.7 (95% CI, 1.6-4.4) for participants with Pfizer, Moderna and Janssen primary schedules. [Dunkle, L. M., 2023 ]
Effectiveness results
Andrews N et al. was a case-control study (Test-negative) conducted in the United Kingdom. The study included 893,845 eligible tests in those aged 18 years and over. The objective was to estimate the effectiveness of the Pfizer and Moderna booster vaccines against the symptomatic disease, hospitalization, and death in adults in England. The study results showed that the booster dose was associated with an absolute vaccine efficacy from 14-34 days after a Pfizer booster of 94.4% (95% CI 94.1 to 94.7) following either an AstraZeneca or Pfizer primary scheme in individuals 50 years and older. With a Moderna booster, absolute vaccine effectiveness was 97.0 (95% CI 96.0 to 97.8) after an AstraZeneca primary scheme and 94.8% (95% CI 92.7 to 96.3%) Pfizer primary scheme [Andrews N, 2022 ].
Tan SHX et al was a comparative cohort study conducted in China. Rates and severity of SARS-CoV-2 infections between September 15 and October 31, 2021, among those eligible to receive vaccine boosters between September 15 and October 15, 2021, were analyzed based on official data reported to the Singapore Ministry of Health. The adjusted incidence rate ratio (2 doses of BNT162b2 plus mRNA-1273 booster) for PCR–confirmed infections was 0.177 (95% CI 0.138 to 0.227) and 0.078 (95% CI 0.011 to 0.560) for severe infection. The Adjusted incidence rate ratio (2 doses of mRNA-1273 plus BNT162b2) for PCR–confirmed infections was 0.140 (95% CI 0.052 to 0.376) [Tan SHX, 2022 ].
Andrews N et al. was a case-control study conducted in England. The study enrolled 2,663,549 vaccinated participants: 204,154 cases for Delta variant, 886,774 cases for Omicron variant and 1,572, 621 test-negative controls. The study analyzed information from national databases, Pillar 1, Pillar 2, NIMS and NHS regarding Covid-19 vaccination, testing, and variants from November 25, 2021, through January 12, 2022. Moderna effectiveness against Delta variant for symptomatic infection was 57.4% (95% CI 52.6 to 61.8) 4 weeks after the first dose, 80.4% (95% CI 67.3 to 88.2) 25 weeks after the second dose, 94.7% (95% CI 89.3 to 97.3) 2-4 weeks after a Pfizer-BioNTech booster and 96.4% (95% CI 91.4 to 98.5) 2-4 weeks after Moderna booster [Andrews N, 2022 ].
Young-Xu Y et al. was a case-control study with matched test-negative design conducted in the United States. The study used records and COVID-19 laboratory test data from the Veterans Health Administration (VHA), which includes 1293 healthcare facilities that attend US veterans. Positive tests during January 2022 were presumed to be Omicron SARS-CoV-2 infections. Each case (positive test) was matched with up to four controls (negative tests). Vaccine effectiveness was estimated through the number of infections, hospitalizations, and death within 30 days of a positive test. The vaccine effectiveness (VE) against omicron infection after two mRNA vaccine doses was 12% (95% CI 10 to 15) and increased to 64% (95% CI 63 to 65) after the booster mRNA dose. The VE against hospitalizations was 63% (95% CI 58 to 67) after two mRNA vaccine doses and increased up to 89% (95% CI 88 to 91) after the booster mRNA dose. The VE against death after 2 mRNA vaccine doses was 77% (95% CI 67 to 83) and increased to 94% (CI 95% CI 90 to 96) after the booster mRNA dose [Young-Xu Y, 2022 ].
Ng OT et al was cohort study conducted in Singapore. The study included 2,441,581 eligible individuals. It was based on data from the Singapore Ministry of Health’s (MOH) official COVID-19 database, including individuals who had received 2 or 3 doses of mRNA vaccines (by Pfizer-BioNTech or Moderna) or inactivated vaccines (by Sinovac or Sinopharm) and notified infections from December 27th 2021 to March 10th 2022. Effectiveness Heterologous Booster against COVID-19 Infeccion was 35.6% (95%CI 32.8-38.3) (wo doses of Moderna and booster dose with Pfizer.[Ng OT, 2022 ]
Buchan et al. conducted a test-negative case-control study using linked provincial databases for SARS-CoV-2 laboratory testing, reportable disease, COVID-19 vaccination and health administration in Ontario (Canadá) to estimate the vaccine effectiveness (VE) against symptomatic infections and severe outcomes associates with these infections. Of 134,435 total participants (> 18 years older), 16,087 were Omicron-positive cases , 4261 were Delta-positive cases, and 114 087 were test-negative controls. Symptomatic Infection against OMICRON BNT16b2: 60% (CI 95% 55-65). VE against Omicron severe outcome BNT16b2: 95% (95% CI 87-98). VE against Delta symptomatic infection BNT16b2: 97% (95% CI 96-98). VE against Delta severe outcome BNT16b2: 99% (95% CI 98-99). [Buchan SA, 2022 ]
Lin DY et al, was a comparative cohort study conducted in the USA. The study included 10,600,823 individuals, among which were 2,771,364 cases of COVID-19. IBased on data from the North Carolina COVID-19 Surveillance System and the Covid-19 Vaccine Management System, including data from residents of North Carolina from December 11, 2020, to September 8, 2021. Vaccine effectiveness of Moderna booster after Pfizer-BioNTech primary schedule was 68.4% (95%CI 66.2 to 70.5) after 1 month, the effectiveness of Pfizer-BioNTech vaccine booster after Moderna primary schedule was 66.1% (95%CI 61.9 to 70.0). [Lin DY, 2022 ].
Vivaldi et al conducted a population based cohort study (COVIDENCE UK) to identify risk factors for SARS-CoV-2 infection after primary and booster vaccinations. This UK study in adults (≥16 years) vaccinated against SARS-CoV-2, assessed risk of breakthrough SARS-CoV-2 infection up to February 2022, for participants who completed a primary vaccination course (ChAdOx1 nCoV-19 or BNT162b2) and those who received a booster dose (BNT162b2 or mRNA-1273). Primary vaccination with ChAdOx1 (vs BNT162b2) was associated with higher risk of infection in both post-primary analysis (adjusted hazard ratio 1,63, 95% CI 1,41–1,88) and after an mRNA-1273 booster (1,26 [1,00–1,57] vs primary and booster BNT162b2 schedules). [Vivaldi G, 2022 ]
Monge S et al, was a nationwide Cohort study conducted in Spain. We linked data from three nationwide population registries in Spain (Vaccination Registry, Laboratory Results Registry, and National Health System registry) . In this study were included 7, 036, 433 participantes ≥ 40 years . The aim of this study was to estimate the effectiveness of mRNA-based vaccine boosters against infection with the omicron variant. The estimated effectiveness from day 7 to 34 after a booster was 51.3% (95%CI 50.2-52.4), with Pfizer Booster was 46,2% (95% CI 43,5–48,7). Estimated effectiveness was 43,6% (95% CI 40,0 –47,1) when the booster was administered between 151 days and 180 days after complete vaccination and 52,2% (95% CI 51,0–53,3) if administered more than 180 days after primary scheduled completion.[Monge S, 2022 ]
Stowe et al. conducted a test-negative case-control study in UK, to estimate Vaccine Effectiveness (VE) against hospitalisation with the Omicron and Delta variants using PCR testing linked hospital records (Emergency Care Data Set; ECDS). The total number of tests in the study period was 409,985 of which 115,720 were cases and 294,265 controls.
VE against hospital admissions from ECDS within 14 days of the test date by the Omicron variant in symptomatic individuals 18 to 64 years of age:
Primary Schedule ChAd0x1-S Booster mRNA-1273
After 14-34 days: 88.3% (95% CI 84.3 to 91.3)
After 70+ days: 74.1% (95% CI 56.3 to 84.7)
Primary Schedule BNT162b2 Booster mRNA-1273
After 14-34 days: 87.3% (95% CI 81.2 to 91.3)
After 70+ days: 60.6% (95% CI 27.7 to 78.5)
VE against hospital admissions from ECDS within 14 days of the test date by the Omicron variant in symptomatic individuals 65 years of age and older:
Primary Schedule ChAd0x1-S Booster mRNA-1273
After 14-34 days: 98.1% (95% CI 92.1 to 99.5)
After 70+ days: 89.6% (95% CI 73.8 to 95.9)
Primary Schedule BNT162b2 Booster mRNA-1273
After 7-13 days: 89.0% (95% CI 17.2 to 98.5)
After 14-34 days: 91.2% (95% CI 75.5 to 96.9)
Grewal R et al. was a case-control study (test negative design) conducted in the United States. The aim of this study was to estimate the marginal effectiveness of a fourth versus third dose and the vaccine effectiveness of the mRNA COVID-19 vaccines BNT162b2 and mRNA-1273 against any infection, symptomatic infection, and severe outcomes (hospital admission or death) related to the Omicron variant. Vaccine effectiveness of two doses of Pfizer and Moderna booster against the Omicron variant against any infection was 36% (95% CI, 28% to 44%), against symptomatic infection was 57% (95% CI, 40% to 69%) and against severe outcomes 81% (95% CI, 67% to 89%). [Grewal R, 2022 ].
Agrawal et al was a retrospective cohort study conducted in the United Kingdom that included 16,208,600 participants, of which 7,589,080 received a Pfizer-BioNTech primary schedule and 8,619,520 received a ChAdOx1 primary schedule. The study was based on data from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database, Vaccine Management System, Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II), and Secure Anonymised Information Linkage Databank platform, during the Omicron period, between December 2021 and February 2022. The adjusted Rate Ratio (aRR) 3-5 weeks after booster vaccination against hospitalization was 0.58 (95% CI, 0.46-0.73) for the Pfizer-BioNTech primary schedule and Moderna booster group and 0.41 (95% CI, 0.33-0.50) for the ChAdOx1 primary schedule and Moderna booster group. [Agrawal U, 2022 ]
Baum U et al was a cohort study conducted in Finland including 896,220 participants aged 70 years and older. The study was based on a nationwide register-based cohort, between December 27th 2020 and March 31st 2022. Vaccine effectiveness (VE) of the booster against hospital admission was 91% (95% CI, 87% to 94%) for the Pfizer schedule+Moderna booster, 91% (95% CI, 81% to 96%) for the Moderna schedule+Pfizer booster, and 94% (95% CI, 92% to 98%) for the AstraZeneca schedule+Moderna booster. VE against ICU admission was 92% (95% CI, 79% to 97%) for the Pfizer schedule+Moderna booster, 100% for the Moderna schedule+Pfizer booster, and 100% for the AstraZeneca schedule+Moderna booster. [Baum U, 2022 ]
Intawong K et al was a test-negative case-control study conducted in Thailand that included 36,170 participants, 14,682 cases and 21,488 controls. Based on data from the Epid-CM platform, including participants aged 18 years and older, between October 2021 and April 2022. The aim was to assess the effectiveness of different booster doses. The adjusted vaccine effectiveness (VE) against infection during the omicron period after the third dose was 31% (95% CI, 15% to 44%) for the Pfizer-BioNTech booster, 26% (95% CI, 8% to 40%) for the AstraZeneca booster and 31% (95% CI, 13% to 45%) for the Moderna booster. The adjusted VE after the fourth dose was 71% (95% CI, 60% to 79%) for the Pfizer-BioNTech booster, 73% (95% CI, 48% to 89%) for the AstraZeneca booster, and 71% (95% CI, 59% to 79%) for the Moderna booster. [Intawong K, 2022 ]
Yuanyuan F et al. was an observational study to analyze vaccination status and SARS-CoV-2 infection data from more than 10.4 million participants in the national COVID Cohort Collaborative during an 18-month-period (December 2020 to June 2022) in the United States. Vaccine Effectiveness (VE) against COVID-19 infection was 46.19% (95% CI, 43.28% to 48.99%) for the Pfizer/Pfizer/Moderna schedule, and 42% (95% CI, 39.38% to 44.54%) for the Moderna/Moderna/Pfizer schedule. VE against COVID-19-related death was 89.56% (95% CI, 85.75% to 92.61%) for the Pfizer/Pfizer/Moderna schedule, and 85.83% (95% CI, 82.49% to 88.70%) for the Moderna/Moderna/Pfizer schedule. [Yuanyuan Fu, 2022 ]
Nittayasoot et al., conducted a test negative case-control study to examine the effectiveness of COVID-19 vaccines during January to April 2022 in Thailand. They analyzed secondary data from four main national health data bases: Co-Lab, Co-Ward, COVID-10 Death and MOPH-IC, using the national identification numbers of each individual as a unique identifier to link the same person across databases. They obtained a total of 3,059,616 records including: 1,015 cases of COVID-19 pneumonia requiring invasive ventilation from 652,854 cases with SARS-CoV-2 detection and 2,046,762 controls or non-SARS-CoV-2 detection. Vaccine Effectiveness against pneumonia requiring invasive ventilation for schedule: ChAdOx1 + ChAdOx1 + Moderna was 87.69% (95% CI, 46.60% to 97.16%), ChAdOx1 + Pfizer + Moderna was 100.00% (95% CI, 99.99% to 100.00%) and Coronavac + Coronavac + Moderna + Moderna was 100.00% (95% CI, 99.99% to 100.00%). [Nittayasoot N, 2022 ]
Huiberts A et al. was a prospective cohort study conducted in Netherlands that included 27,646 participants from the Omicron period: 3,802 received primary vaccination schedule, 23,352 received first booster dose and 492 were unvaccinated. The primary outcome was contracting SARS-CoV-2 between July 12th 2021 and June 6th 2022. Vaccine effectiveness (VE) against contracting COVID-19 during the Omicron BA.1-2 period was 15.8% (95% CI, -26.3% to 43.9%), 68.3% (95% CI, 63.1% to 72.8%) and 67.6% (95% CI, 60.1% to 73.7%) for Moderna primary schedule, mRNA primary schedule with Moderna booster and AstraZeneca primary schedule with Moderna booster, respectively. VE against contracting COVID-19 during the Delta period was 100% (95% CI, 0% to 100%) and 100% (95% CI, 0% to 100%) for Moderna primary schedule and mRNA primary schedule with Moderna booster, respectively. [Anne J. Huiberts, 2023 ]
Cerqueira-Silva T et al was a case-control study, test-negative design, conducted in Brazil and Scotland. The study included 5,832,210 participants: 5,276,385 from Brazil and 555,825 from Scotland. This study assessed vaccine effectiveness of a mRNA booster after AstraZeneca or Pfizer primary schedule during the period of Omicron dominance. Vaccine effectiveness against severe outcomes was 93.5% (95% CI, 93% to 94%), 94.4% (95% CI, 87.7% to 97.5%) and 92.7% (95% CI, 91% to 94%) with AstraZeneca primary schedule and Pfizer booster, AstraZeneca primary schedule and Moderna booster, and Pfizer homologous booster, respectively. [Cerqueira-Silva T, 2023 ]
Kamal SM et al was a comparative cohort study conducted in Saudi Arabia that included data from 1,500 vaccinated participants: 503 AstraZeneca, 521 Pfizer, and 476 Moderna, and 1,500 in the control group. The aim was to assess the effectiveness of the AstraZeneca, Pfizer, and Moderna vaccines, and two Pfizer boosters. Relative risk of infection after the first booster was 0.015 (95% CI, 0.0049-0.047). [Kamal SM, 2023 ]
Tenforde MW et al was a case-control study conducted in the United States that included data from 78,170 emergency department encounters: 8,986 cases and 69,184 controls. This study assessed the effectiveness of a bivalent booster dose among immunocompetent adults during September 13th to November 18th 2022 (Omicron BA.5 sublineage predominance). Vaccine effectiveness of bivalent booster dose against emergency department or urgency care encounters was 56% (95% CI, 50% a 61%). [Tenforde MW, 2023 ]
Safety of the vaccine
Safety of the vaccine in preclinical studies
The Moderna COVID-19 vaccine was tested in non-human primates. There were no vaccine-related adverse events noted. No cases of death or pathological changes in the lung were noted [Corbett KS, 2020 ].
Reproductive toxicity
A study performed in rats assessing postnatal reproductive toxicity of the Moderna COVID-19 vaccine was submitted to FDA on December 4, 2020. FDA review concluded that a dose of 100 μg given prior gestation periods did not have any adverse effects on female reproduction, fetal/embryonal development, or postnatal developmental [FDA, 2020 ]
Developmental and reproductive toxicology (DART) studies in rats concluded that the vaccine at a dose of 100 μg, given prior to mating and during gestation periods, did not have any adverse effects (including on female reproduction, fetal/embryonic development, or postnatal developmental).
Safety of the vaccine in clinical trials
Main safety outcomes of Moderna COVID-19 vaccine
Key messages
Moderna COVID-19 vaccine increase the risk of any adverse events.
Moderna COVID-19 vaccine did not increase the risk of serious adverse events.
Any adverse event after the 2nd dose (within 7 days after injection)
The relative risk of any adverse event after the 2nd dose in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 1.94 (95% CI 1.58 to 2.38). This means Moderna COVID-19 vaccine increased the risk of any adverse event after the 2nd dose by 94%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: any adverse event after the 2nd dose. Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 6255 people not receiving Moderna COVID-19 vaccine out of 14578 presented this outcome (439 per 1000) versus 13556 out of 14691 in the group that did receive it (851 per 1000). In other words, 412 more people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk increase of 41.2%, or that the intervention increased the risk of any adverse event after the 2nd dose by 41.2 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTH is 2. Which means that 2 people need to receive the vaccine for one of them to experienced any adverse event after the 2nd dose.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.
Local adverse events after the 2nd dose (within 7 days after injection)
The relative risk of local adverse events after the 2nd dose in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 3.67 (95% CI 2.26 to 5.95). This means Moderna COVID-19 vaccine increased the risk of local adverse events after the 2nd dose by 267%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: local adverse events after the 2nd dose. Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 2757 people not receiving Moderna COVID-19 vaccine out of 14578 presented this outcome (200 per 1000) versus 13029 out of 14691 in the group that did receive it (734 per 1000). In other words, 534 more people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk increase of 53.4%, or that the intervention increased the risk of local adverse events after the 2nd dose by 53.4 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTH is 2. Which means that 2 people need to receive the vaccine for one of them to experienced local adverse events after the 2nd dose.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.
Systemic adverse events after the 2nd dose (within 7 days after injection)
The relative risk of systemic adverse events after the 2nd dose in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 2.98 (95% CI 1.56 to 5.67). This means Moderna COVID-19 vaccine increased the risk of systemic adverse events after the 2nd dose by 198%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: systemic adverse events after the 2nd dose. Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 5343 people not receiving Moderna COVID-19 vaccine out of 14578 presented this outcome (342 per 1000) versus 11678 out of 14691 in the group that did receive it (1018 per 1000). In other words, 676 more people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk increase of 67.6%, or that the intervention increased the risk of systemic adverse events after the 2nd dose by 67.6 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTH is 1. Which means that 1 people need to receive the vaccine for one of them to experienced systemic adverse events after the 2nd dose.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.
Non-serious adverse events
The total number of non-serious adverse events was not reported as a group, so it was not possible to estimate the effect for this outcome.
The most common non-serious adverse reactions associated with Moderna COVID-19 vaccine were pain at the injection site (91.6%), followed by fatigue (68.5%), headache (63.0%), muscle pain (59.6%), joint pain (44.8%), and chills (43.4%); local adverse reactions occurred more frequently after second dose, and were generally less frequent in younger participants (≥65 years of age).
Serious adverse events (within 28 days after any injection)
The relative risk of serious adverse events in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 0.95 (95% CI 0.73 to 1.25). No statistically significant differences between groups were found for serious adverse events.
Figure - Forest plot of risk ratio meta-analysis. Outcome: any adverse event after the 2nd dose. Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 104 people not receiving Moderna COVID-19 vaccine out of 104 presented this outcome (65 per 10000) versus 98 out of 15184 in the group that did receive it (62 per 10000). In other words, 3 less people per 10000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk of 0.03%, or that the intervention reduced the risk of serious adverse events by 0.03 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTB is 3333. Which means that 3333 people need to receive the vaccine for one of them to experienced serious adverse events.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as moderate. The certainty of the evidence is based in the following judgments: Risk of bias: no concerns; Inconsistency: no concerns; Indirectness: no concerns; Imprecision: the information provides from a small sample; Publication bias: no concerns.
Safety of the vaccine in subgroups
Any adverse event after the 2nd dose (Females subgroup) (within 7 days after 2nd injection)
The relative risk of any adverse event after the 2nd dose in the females subgroup in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 1.96 (95% CI 1.91 to 2.01). This means Moderna COVID-19 vaccine increased the risk of any adverse event after the 2nd dose in the females subgroup by 96%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: any adverse event after the 2nd dose in the females subgroup. Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 3292 people not receiving Moderna COVID-19 vaccine out of 6847 presented this outcome (428 per 1000) versus 6635 out of 7045 in the group that did receive it (838 per 1000). In other words, 410 more people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk increase of 41%, or that the intervention increased the risk of any adverse event after the 2nd dose in the females subgroup by 41 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTH is 2. Which means that 2 people need to receive the vaccine for one of them to experienced any adverse event after the 2nd dose in the females subgroup.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.
Any adverse event after the 2nd dose (Males subgroup) (within 7 days after 2nd injection)
The relative risk of any adverse event after the 2nd dose in the males subgroup in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 2.36 (95% CI 2.29 to 2.43). This means Moderna COVID-19 vaccine increased the risk of any adverse event after the 2nd dose in the males subgroup by 136%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: any adverse event after the 2nd dose in the males subgroup. Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 2963 people not receiving Moderna COVID-19 vaccine out of 7731 presented this outcome (428 per 1000) versus 6921 out of 7646 in the group that did receive it (1011 per 1000). In other words, 583 more people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk increase of 58.3%, or that the intervention increased the risk of any adverse event after the 2nd dose in the males subgroup by 58.3 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTH is 2. Which means that 2 people need to receive the vaccine for one of them to experienced any adverse event after the 2nd dose in the males subgroup.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.
Any adverse event after the 2nd dose (≥65 years) (within 7 days after 2nd injection)
The relative risk of any adverse event after the 2nd dose in the ≥65 year old participants in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 2.45 (95% CI 2.34 to 2.56). This means Moderna COVID-19 vaccine increased the risk of any adverse event after the 2nd dose in the ≥65 year old participants by 145%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: any adverse event after the 2nd dose in the ≥65 year old participants . Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 1334 people not receiving Moderna COVID-19 vaccine out of 3649 presented this outcome (428 per 1000) versus 3304 out of 3691 in the group that did receive it (1048 per 1000). In other words, 620 more people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk increase of 62%, or that the intervention increased the risk of any adverse event after the 2nd dose in the ≥65 year old participants by 62 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTH is 2. Which means that 2 people need to receive the vaccine for one of them to experienced any adverse event after the 2nd dose in the ≥65 year old participants .
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.
Any adverse event after the 2nd dose (12-17 years) (within 7 days after 2nd injection)
The relative risk of any adverse event after the 2nd dose in children between 12 to 17 years of age in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 1.74 (95% CI 1.66 to 1.83). This means Moderna COVID-19 vaccine increased the risk of any adverse event after the 2nd dose in children between 12 to 17 years of age by 74%, compared with placebo vaccine.
Figure - Forest plot of risk ratio meta-analysis. Outcome: any adverse event after the 2nd dose in children between 12 to 17 years of age. Comparison: Moderna COVID-19 vaccine versus placebo vaccine
In the trial identified in this review, 680 people not receiving Moderna COVID-19 vaccine out of 1220 presented this outcome (428 per 1000) versus 2405 out of 2478 in the group that did receive it (745 per 1000). In other words, 317 more people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk increase of 31.7%, or that the intervention increased the risk of any adverse event after the 2nd dose in children between 12 to 17 years of age by 31.7 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTH is 3. Which means that 3 people need to receive the vaccine for one of them to experienced any adverse event after the 2nd dose in children between 12 to 17 years of age.
Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.
Summary of findings (iSoF)
Safety of the vaccine in subgroups
Sex
Randomized trials
The proportion of females in the COVE trial was 47.3% (14366 out of 30351 participants) [Baden LR, 2021 ].
Safety profile of Moderna COVID-19 vaccine was similar across sex groups.
Other comparative studies
Li LL et al. included 3,118,802 participants who had received one dose of a SARS-CoV-2 mRNA vaccine and 2,979,326 who had received two doses (1,389,401 Pfizer and 1,589,925 Moderna). Data were collected during the period from December 12, 2020, to August 21, 2021. The study results showed that, Overall, two-dose mRNA vaccine regimens are safe in a population with many comorbidities. Weakness, muscle aches, fever, mental status changes, falls, dehydration and acute kidney injury were transiently increased after vaccination, especially after the second dose. Among patients with prior SARS-CoV-2 infection, there was an increased risk of hospitalization (absolute risk 1:1000) [Li LL, 2022 ].
Age
Randomized trials
25% (7512/30351) of the participants in the COVE trial were aged 65 years or over (mean age: 70.6 years; range: 40-95 years) [Baden LR, 2021 ].
Severe adverse reactions were generally less frequent in participants ≥65 years of age as compared to younger participants [FDA, 2020 ].
Lymphadenopathy (axillary swelling and tenderness of the vaccination arm) was observed in 12.4% of vaccine recipients ≥65 years of age, as compared with 5.8% of placebo recipients [FDA, 2020 ].
The phase 2, open-label study QHD00028 is currently evaluating the efficacy/safety of the vaccine in fully vaccinated adults with mRNA-1273 65 years of age and older [Sanofi Pasteur, a Sanofi Company, 2021 ].
The phase 4, randomized controlled trial mRNA-1273-D3-2021 is currently evaluating the efficacy/safety of the vaccine in vaccinated residents ≥65 years that received [Mark Loeb, 2021 ].
Children and adolescents
Randomized trials
The TeenCove or study P203 (NCT04649151) was a phase 2/3 trial sponsored by Moderna evaluating vaccine efficacy in adolescents from 12 to 17 years of age. Results of the study showed that in the mRNA-1273 group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 93.1% and 92.4%, respectively), headache (in 44.6% and 70.2%, respectively), and fatigue (in 47.9% and 67.8%, respectively); in the placebo group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 34.8% or 30.3%, respectively), headache (in 38.5% and 30.2%, respectively), and fatigue (in 36.6% and 28.9%, respectively). No serious adverse events related to mRNA-1273 or placebo were noted [Ali K, 2021 ].
P204 study (mRNA-1273-P204) is an ongoing phase 2/3, randomized trial sponsored by ModernaTX, Inc. It was first registered in March 15, 2021 and plans to enroll 6750 participants with children between 6 months of age and less than 12 years of age, finalizing in June 10, 2023. Participants will be randomized to receive intramuscular injections of the vaccine at different doses (defined in the different states of the study), 28 days apart, on Day 1 and Day 29. [ModernaTX, Inc., 2021 ].
Other comparative studies
Cheng DR et al was a population based study conducted in Australia. The study included 454,974 12 to17 years old participants who had received 871,689 mRNA doses (782,964 Pfizer and 88,725 Moderna). The aim was to describe myocarditis adverse events following immunisation reported following any COVID-19 mRNA vaccines in the adolescent population. Confirmed myocarditis reporting rates were8.3 per 100 000 doses in this age group (aggregated data for both mRNA vaccines). [Cheng DR, 2022 ]
Cristina Morciano et al was a self-controlled case series study that included 15,986,009 participants who received at least one dose of Covid-19 vaccine: 10,833,284 with Pfizer vaccine, 1,706,979 with Moderna vaccine, 2,863,950 with AstraZeneca vaccine and 581,796 with Janssen vaccine. This study investigated the risk of Guillain Barré Syndrome after vaccination with anti-COVID-19 vaccines. Relative incidence of Guillain Barré Syndrome for the second dose of Moderna was 6,83 (95% CI, 2,14-21,85). [Cristina Morciano, 2023 ]
Pregnancy
Other comparative studies
Nakahara A et al. included 83 vaccinated pregnant women that received mRNA COVID-19 vaccines (Moderna or Pfizer). These pregnant women were age-matched with 166 female controls. Safety was assessed as any vaccine-related complaint as defined in the original safety data. Results showed a frequency of complaint following vaccine administration of 18.1% in the pregnant group and 16.9% in the non-pregnant group. The most frequent local and systemic reactions in Pregnant females were: fever 4.8%, Cough/Shortness of Breath 4.8 %, Vomiting/Diarrhea 4.8%. Complaint frequency was higher after the second dose (12.3 %) than after the first dose (6%) [Nakahara A, 2022 ].
Aharon D et al. included 222 vaccinated (Pfizer =119 or Moderna =103) patients and 983 unvaccinated patients who underwent controlled ovarian hyperstimulation cycles between February and September 2021. Data collected included oocyte, fertilization, and embryo development parameters, as well as results of preimplantation genetic testing for aneuploidy among cycles in which testing was performed. The study showed that the administration of Pfizer or Moderna COVID-19 vaccine was not associated with an adverse effect on stimulation or early pregnancy outcomes after in vitro fertilization. The fertilization rate for the controlled ovarian hyperstimulation cohort was 80.7% (95% CI 78.4 to 83.0) in the vaccinated group and 78.7% in unvaccinated groups (95% CI 77.5 to 80.0). No differences were observed between vaccinated and unvaccinated patients on univariate analysis in the secondary outcomes of eggs retrieved, mature oocytes retrieved, mature oocytes ratio, or blastulation rate. In cycles in which preimplantation genetic testing for aneuploidy was performed, vaccinated patients had a proportion of euploid embryos of 48.8% (95% CI 44.1 to 53.6) compared with 42.5% (95% CI 40.2 to 44.9) in unvaccinated patients [Aharon D, 2022 ].
Kachikis et al . analyzed a convenience sample of adults enrolled in the online prospective study who were pregnant, lactating, or neither pregnant nor lactating at the time of their booster or third dose was eligible for this follow-up survey; 17,014 (97.2%) completed the follow-up survey. 16, 989 individuals who reported their vaccine type for their booster or third dose, most received the BNT162b2 (10,319 [60.7%]) or mRNA-1273 (6651 [39.2%]) vaccines. After a COVID-19 booster or third dose, 82.8% reported a local reaction, and 67.9% reported at least 1 systemic symptom. Compared with individuals who were neither pregnant nor lactating, pregnant participants were more likely to report any local reaction to a COVID-19 booster or third dose (adjusted odds ratio [aOR], 1.2; 95% CI, 1.0-1.4; P = 0.01) but less likely to report any systemic reaction (aOR, 0.7; 95% CI, 0.6-0.8; P<0.001). Most pregnant (1961 of 2009 [97.6%]) and lactating (9866 of 10,277 [96.0%]) individuals reported no obstetric or lactation concerns after vaccination. [Kachikis A, 2022 ]
Sadarangani M et al was a cohort study conducted in Canada. This study aimed to determine the frequency and nature of significant health events among pregnant females after COVID-19 vaccination, compared with unvaccinated pregnant controls and vaccinated non-pregnant individuals. Data were collected primarily by self-reported survey after both vaccine doses. Most pregnant participants had received BNT162b2 (3414 received dose one and 1892 received dose two) or mRNA-1273 (2183 received dose one and 1216 received dose two) COVID-19 vaccines. Pregnant vaccinated females had decreased odds of a significant health event compared with non-pregnant vaccinated females after both dose one (aOR 0.63 95% CI 0.55 to 0.72]) and dose two (aOR 0.62 [0.54 to 0.71]) of any mRNA vaccination. Pregnant vaccinated females had an increased odds of a significant health event within 7 days of the vaccine after dose two of mRNA-1273 (adjusted odds ratio 4.4 95% CI 2.4 to 8.3]) compared with pregnant unvaccinated controls and 1.3 (95% CI 0.67 to 2.42) after second dose of Pfizer vaccine. [Sadarangani M, 2022 ]
DeSilva et al. was a retrospective matched-cohort study including 45,232 pregnant women between 16-49 years, who received the Pfizer-BioNTech, Moderna or Janssen vaccines and matched unvaccinated controls. The adjusted rate ratios (aRR) for acute maternal outcomes during days 0-21 after receiving the Moderna vaccine were 1.99 (95% CI, 1.14-3.46) for skin and soft tissue or local allergic reactions, 4.65 (95% CI, 2.13-10.15) for fever, 2.88 (95% CI, 1.93-4.3) for malaise and 1.78 (95% CI, 0.93-3.4) for lymphadenopathy. [DeSilva M, 2022 ]
Mansour O et al was a prospective cohort study conducted in the United States including 2129 pregnant women from the C-VIPER cohort who received at least one dose of Pfizer or Moderna vaccines. The estimated overall cumulative risk of spontaneous abortion (SAB) by gestational week 20 was 13.4% (95% CI, 8.3% to 16.9%), which is within the range estimated by both population-based cohorts and v-safe. The cumulative risk of SAB by week 20 for Pfizer was 10.9% (95% CI, 5.9% to 14.7%), The cumulative risk of SAB by week 20 for Moderna was 20.6% (95% CI, 8.8% to 29.4%). [Mansour O, 2023 ]
Morgan et al was a retrospective cohort study conducted in the United States that included 15,865 pregnant patients: 2,069 in the vaccinated group and 13,796 in the unvaccinated group. The study compared the frequency of adverse outcomes in between pregnant patients who received mRNA vaccines and unvaccinated patients. Vaccination was associated with a lower incidence of perinatal death (aOR 0.20 [95% CI, 0.05–0.88]), rates of preterm delivery (aOR 0.63 [95% CI, 0.48–0.82]), neonates with very low birth weight (aOR 0.35 [95% CI, 0.15–0.84]), and neonatal intensive care unit admission (aOR 0.66 [95% CI, 0.52–0.85]) aOR = adjusted Odds Ratio. [Morgan JA, 2023 ]
Breast-feeding
Randomized trials
No clinical trial evaluating vaccines to prevent COVID-19 has included breast-feeding females.
Other comparative studies
Kachikis et al . analyzed a convenience sample of adults enrolled in the online prospective study who were pregnant, lactating, or neither pregnant nor lactating at the time of their booster or third dose was eligible for this follow-up survey; 17,014 (97.2%) completed the follow-up survey. 16, 989 individuals who reported their vaccine type for their booster or third dose, most received the BNT162b2 (10,319 [60.7%]) or mRNA-1273 (6651 [39.2%]) vaccines. After a COVID-19 booster or third dose, 82.8% reported a local reaction, and 67.9% reported at least 1 systemic symptom. Compared with individuals who were neither pregnant nor lactating, pregnant participants were more likely to report any local reaction to a COVID-19 booster or third dose (adjusted odds ratio [aOR], 1.2; 95% CI, 1.0-1.4; P = 0.01) but less likely to report any systemic reaction (aOR, 0.7; 95% CI, 0.6-0.8; P<0.001). Most pregnant (1961 of 2009 [97.6%]) and lactating (9866 of 10,277 [96.0%]) individuals reported no obstetric or lactation concerns after vaccination. [Kachikis A, 2022 ]
Immunocompromised persons
Randomized trials
The phase 3, multicenter randomized controlled, open-label, 2-arm sub-study pilot trial COVERALL is currently evaluating the efficacy/safety of the vaccine in patients included in the Swiss HIV Cohort Study or the Swiss Transplant Cohort Study [University Hospital, Basel, Switzerland, 2021 ].
The randomized, multi-site, adaptive, open-label clinical trial DAIT ACV01 is currently evaluating the efficacy/safety of the vaccine in participants with autoimmune disease requiring immunosuppressive medications [National Institute of Allergy and Infectious Diseases (NIAID), 2021 ].
The phase 2, randomized, single blinded study Boost-TX is currently evaluating the efficacy/safety of the vaccine in kidney transplant recipients [Medical University of Vienna, 2021 ].
Safety of the vaccine post-authorization
Comparative studies
Albalawi O et al. was a study conducted in the United States. The study enrolled the general population that received Pfizer-BioNTech, Moderna, and Janssen vaccines. Based on data from Vaccine Adverse Event Reporting System (VAERS) between 15 December 2020 to 19 March 2021. Total non-serious reporting rate was 28.4 per 100,000 doses administered and total serious reporting rate was 5.6 per 100,000 doses administered. Results of the study showed that the Moderna group had more deaths than the Pfizer-BioNTech group (7% 95% CI-14% to 33%). [Albalawi OM, 2021 ].
Maxime Taquet et al. was a retrospective cohort conducted in the United States. The study enrolled 537 913 participants: 389,034 with COVID-19 and 389,034 with mRNA vaccine. The aim was to estimate the absolute risk of cerebral venous thrombosis (CVT) and portal vein thrombosis (PVT) in the two weeks following a diagnosis of COVID-19, and to assess the relative risks (RR) compared to influenza or the administration of an mRNA vaccine against COVID-19. RR for CVT was 6.33 (95% CI, 1.87-21.4) for Pfizer or Moderna vaccine versus COVID-19 (control) and 2.67 (95% CI, 1.04-6.81) for Pfizer or Moderna vaccine versus Influenza (control). RR of PVT was 4.46 (95% CI, 3.12-6.37) for Pfizer or Moderna vaccine versus COVID-19 (control) and 1.43 (95% CI, 1.10-1.88) for Pfizer or Moderna vaccine versus Influenza (control). [Taquet M, 2021 ]
Magnus MC et al. was a case-control study conducted in Norway. The study enrolled 13,956 participants, with 103 participants receiving Moderna vaccine. Based on data from Norwegian registries on first-trimester pregnancies, Covid-19 vaccination, background characteristics, and underlying health conditions of all women who were registered between February 15 and August 15, 2021, the study reported a miscarriage Adjusted Odds Ratio of 0.84 (95%CI 0.56 to 1.25) in vaccinated individuals [Magnus MC, 2021 ].
Kharbanda EO et al. was a case-control study conducted in the United States. The study enrolled 105,446 participants and was based on a validated pregnancy algorithm, which incorporates diagnostic and procedure codes and electronic health records from 8 health systems data to identify and assign gestational ages for spontaneous abortions and ongoing pregnancies between December 15, 2020, and June 28, 2021. The study results showed a Spontaneous abortions adjusted Odds Ratio of 1.03 (95%CI 0.94 to 1.11) in vaccinated individuals. [Kharbanda EO, 2021 ]
Edelman A et al. was a cohort study conducted in the United States. The study enrolled 3,959 participants: 2,403 vaccine group (55% Pfizer, 35% Moderna, 7% Janssen); 1,556 control group. Based on prospectively tracked menstrual cycle data using the application "Natural Cycles”, between October 2020 and September 2021, the study assessed whether coronavirus disease 2019 (COVID-19) vaccination is associated with changes in cycle or menses length in those receiving vaccination as compared with an unvaccinated cohort. The study results showed a change in menstrual cycle length of less than 1 day compared with prevaccine cycles. The study also reports a mean change of 0.64 days, (98.75% CI 0.27-1.01) after the first dose and a mean change of 0.79 days, (98.75% CI 0.40-1.18) after the second dose when comparing with unvaccinated individuals [Edelman A, 2022 ].
Wesselink AK et al. was a cohort study conducted in the United States and Canada. The study enrolled 2,126 participants: 1,299 vaccine group; 897 control group. Based on questionnaires on sociodemographics, lifestyle, and reproductive and medical histories with follow-up every 8 weeks during December 2020 - September 2021 and followed them through November 2021, the study objective was to examine the associations of female and male COVID-19 vaccination with fecundability, the per-cycle probability of conception. The study results showed that COVID-19 vaccination was not appreciably associated with fecundability, with a female Fecundability Rate (FR) of 1.08 (95% CI 0.95 to 1.23) and a male FR=0.95 (95% CI 0.83 to 1.10) in vaccinated individuals. [Wesselink AK, 2022 ].
Tu TM et al. was a comparative cohort study conducted in Singapore. The study enrolled 62,447 individuals diagnosed with SARS-CoV-2 and 3,006,662 individuals with at least one dose of mRNA-based SARS-CoV-2 vaccine. It was conducted between January 23, 2020, and August 3, 2021, at all public acute hospitals in Singapore, where patients hospitalized with cerebral venous thrombosis (CVT) within 6 weeks of SARS-CoV-2 infection or after mRNA-based SARS-CoV-2 vaccination (Pfizer-BioNTech or Moderna) were identified. Annualized incidence rate of hospitalized CVT cases per 100,000 person-years for Moderna COVID-19 Vaccine was 2.23 (95% CI 0.06 to 12.4) for individuals who received only one dose and 5.18 (95% CI 0.63 to 18.7) for individuals who received 2 doses [Tu TM, 2022 ].
Gallo K et al. was a comparative study conducted in the United State. The study evaluated 580.000 cases from the Vaccination Adverse Event Reporting System. Data for vaccination associated side effects were obtained from VAERS between 1 January and 24 September 2021. The prevalence of adverse events in the general population was assessed based on previously published studies concerning each condition. The OR for Moderna adverse events compared to the general population was: 1 for cerebral thrombosis, 2.2 for Guillán-Barre syndrome, 0.4 for myocarditis and 0.5 for pericarditis [Gallo K, 2022 ].
Goddard K et al. was a comparative cohort study conducted in the United States. The study included 2,891,498 individuals with administered doses of the BNT162b2 vaccine and 1,803,267 with doses of the mRNA-1273 vaccine. Participants aged 18 to 39 years were followed with weekly updated data, supplemented by a review of medical records for cases of myocarditis and pericarditis. The adjusted RR of myocarditis and pericarditis for the 0-7 day risk interval was 9.2 after an mRNA-1273 vaccine. After the second dose of mRNA-1273, RR for myocarditis and pericarditis was 18.8 (95% CI 6.7-64.9) [Goddard K, 2022 ].
Massari M et al. was a self-controlled case study conducted in Italy. The study included 2,861,809 persons aged 12 to 39 years received mRNA vaccines: 2,405,759 received Pfizer–BioNTech vaccine and 456,050 received Moderna vaccine. This study used data on COVID-19 vaccination linked to emergency care/hospital discharge databases. The outcome was the first diagnosis of myocarditis/pericarditis between 27 December 2020 and 30 September 2021. Within the 21-day risk interval, 114 myocarditis/pericarditis events occurred, the relative incidences (RI) were 2.22 (1.00 to 4.91) and 2.63 (1.21 to 5.71) after the first and second dose of Moderna. During the (0 to 7) days risk period, an increased risk of myocarditis/pericarditis was observed after the first dose of Moderna, with an RI of 6.55 (2.73 to 15.72) [Massari M, 2022 ].
Botton J et al. was a self-controlled case series conducted in France. The study included participants (5,253 first dose of mRNA-1273; 4,099 Second dose of mRNA-1273; and 28 third mRNA-1273 dose) aged 18 to 74 years hospitalized for pulmonary embolism, acute myocardial infarction, hemorrhagic stroke, or ischemic stroke between December 27, 2020, and December 20, 2021. This study assessed the short-term risk for severe cardiovascular events after COVID-19 vaccination in France's 46.5 million adults. The primary outcome was hospitalizations for cardiovascular events (Myocardial infarction, pulmonary embolism, or stroke). The Relative Incidence during the second week after the second dose of the mRNA-1273 vaccine for Myocardial Infarction was 1.21 (95 % CI, 0.90 - 1.62), 0.88 (95 % CI, 0.56 - 1.40) for Pulmonary Embolism, 1.12 (95 % CI, 0.77 - 1.62) for Ischemic Stroke, and 0.45 (95 % CI, 0.16 - 1.23) for Hemorrhagic Stroke [Botton J, 2022 ].
Fell DB et al. was a retrospective cohort study conducted in Canada. The study included all liveborn and stillborn infants from pregnancies conceived at least 42 weeks before the end of the study period and with gestational age ≥20 weeks or birth weight ≥500 g [Vaccine product received for dose 1: 34,526 BNT162b2, 8,453 mRNA-1273 (Moderna), 120 Other (ChAdOx1); Vaccine product for those who received two doses of mRNA vaccine during pregnancy: 19,866 BNT162b2+BNT162b2, 5,321 mRNA-1273+mRNA-1273, 4,387 BNT162b2+mRNA-1273 or mRNA-1273+BNT162b2], between 1 May to 31 December 2021. This study assessed the risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy. The primary outcome was preterm birth and very preterm birth events as a live birth before 37 and 32 completed weeks of gestation. [Fell DB, 2022 ]. The adjusted hazard ratio for preterm birth <37 weeks in those who received ≥1 vaccine doses during pregnancy was 1.02 (95% CI 0.96-1.08), 0.96 (95% CI 0.90-1.03) for spontaneous preterm birth <37 weeks, 0.80 (95% CI 0.67 - 0.95) for very preterm birth <32 weeks, 0.98 (95% CI 50.93 - 1.03) for small for gestational age at birth, 0.65 (95% CI 0.51 - 0.84) for Stillbirth [Fell DB, 2022 ].
Imai et al. conducted a comparative case-control study in Japan, with the aim of evaluating the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunuzation stress-related responses (ISRR). 614,151 healthy adult participants received the Moderna vaccine. The individuals who presented IHSR were assigned to group 1, the individuals who presented ISRR were assigned to group 2 and the individuals who did not present any reaction to the control group. 3014 occasions post-immunization adverse reactions were observed in 2913 individuals, 101 individuals showed adverse effects at both doses. 318 events were IHSR in 306 patients (11%) and 2558 were ISRR in 2478 individuals (85%). [Imai K, 2022 ]
Wong HL et al was a retrospective cohort study conducted in United States. The study included data from 15,148,369 people aged 18–64 years with 411 myocarditis or pericarditis cases reported. This study used active surveillance from large health-care databases to quantify and enable the direct comparison of the risk of myocarditis or pericarditis, or both, after mRNA-1273 (Moderna) and BNT162b2 (Pfizer–BioNTech) vaccinations. Incidence rates (IR) for myocarditis or pericarditis in the first 1 to 7 days after COVID-19 mRNA vaccination after dose 2 was 2.17 (95% CI 1.55 to 3.04) per 100,000 person-days for mRNA-1273 vaccine and 32.2 (95% CI –33.90 to 98.30) per 100,000 person-days for Pfizer vaccine. [Wong HL, 2022 ]
Simone A et al was comparative retrospective study conducted in United States. The study included 3,076,660 participants with at least one dose of COVID-19 mRNA vaccines, 2,916,739 with at least two doses of COVID-19 mRNA vaccines and 1,146,254 with at least three doses of COVID-19 mRNA vaccines. This study aimed to evaluate whether a third dose of COVID-19 mRNA (BNT162b2 or mRNA-1273 mRNA) vaccine was associated with an increased risk of myocarditis. Incidence rate ratios of myocarditis in vaccinated individuals compared to control groups were 0.86 (95% CI 0.31 to 1.93) after the first dose, 4.22 (95% CI 2.63 to 6.53) after the second dose and 2.61 (95% CI 1.13 to 5.29) after the third dose (aggregated data from Pfizer-BioNTech and Moderna COVID-19 vaccines) (Aggregated data from Pfizer-BioNTech and Moderna COVID-19 vaccines). [Simone A, 2022 ]
Lloyd PC et al was a retrospective cohort study conducted in United States. The study included data from 9,604,918 doses from the Optum database, 14,146,413 doses from the HealthCore database and 14,146,413 doses from the CVS Health database. This study utilized sequential testing to detect potential safety signals following vaccination by comparing observed rates of adverse events following vaccination to historical background rates. Rate ratios (RR) of observed adverse events rates compared to historical (or expected) rates prior to COVID-19 vaccination from the Optum, HealthCore, and CVS Health Databases were RR 1.03, 0.91 and 1.15 for acute myocardial infarction, RR 0.90, 0.90 and 1.05 for deep vein thrombosis, RR 0.93, 1.19 and 1.36 for pulmonary embolism and RR 1.13, 0.67 and 0.78 for Disseminated Intravascular Coagulation. [Lloyd PC, 2022 ]
Buchan SA et al. was a retrospective cohort study conducted in Canada. The study included data from 19,740,741 doses of mRNA vaccines from Ontario’s COVID-19 vaccine registry and passive vaccine-safety surveillance system. This study aimed to estimate rates of reported myocarditis or pericarditis following receipt of a COVID-19 mRNA vaccine (BNT162b2 or mRNA-1273). The adjusted Rate Ratios (aRR) for myocarditis or pericarditis comparing Moderna with Pfizer-BioNTech by age groups for females were 9.6 (95% CI, 1.9-48.8) in the 18-24 years old group, 1.6 (95% CI, 0.4-6.3) in the 25-39 years old group and 0.5 (0.04-4.3) in the 40 and above years old group. For males, 6.6 (95% CI, 3.3-13.2) in the 18-24 years old group, 5.1 (95% CI, 2.3-11.5) in the 25-39 years old group and 0.8 (95% CI, 0.3-2.7) in the 40 years and above group. [Buchan SA, 2022 ]
Kim JE et al was a retrospective cohort study conducted in South Korea. The study included data from 1,731,147 adverse drug reaction reports related to COVID-19 vaccines from VigiBase, a WHO database, and aimed to evaluate the association between COVID-19 vaccination and the occurrence of Neuralgic Amyotrophy. The Reporting Odds Ratio (ROR) for Neuralgic Amyotrophy after mRNA vaccination was 4.35 (95% CI, 3.2-4.06). [Kim JE, 2022 ]
Calvert C et al was a comparative cohort study conducted in Scotland that data from the COPS study database, including 93,900 pregnant women, 18,780 vaccinated and 75,120 controls. The study assessed the incidence of adverse pregnancy outcomes after COVID-19 vaccination. The adjusted odds ratio after Moderna vaccination for miscarriage was 1.04 (95% CI, 0.76–1.43), and 1.28 (95% CI, 0.55–2.99) for ectopic pregnancy. [Calvert C, 2022 ]
Le Vu S et al. was a case control study conducted in France that used data from National Health Data System (SNDS), focused on the period from May 12th to October 31st 2021. It included 1,612 cases of myocarditis and 16,120 matched controls; 1,613 cases of pericarditis and 16,130 matched controls. The adjusted Odds Ratio (OR) 1-7 days following the second vaccine dose for developing myocarditis was 30 (95% CI, 21–43), and for pericarditis 5.5 (95% CI, 3.3–9). [Le Vu S, 2022 ]
Patone et al. conducted a case series study of 42 842 345 people aged 13 years and older receiving at least 1 dose of COVID-19 vaccines in England between December 1st 2020 and December 15th 2021. They evaluated the association between vaccination and myocarditis. The risk of myocarditis was increased in the first 1-28 days after a second dose of Moderna with an incidence rate ratio of 11.76 (95% CI, 7.25–19.08), and persisted to 2.64 (95% CI, 1.25–5.58) after a booster dose. [Patone M, 2022 ]
Straus W et al was a retrospective cohort study conducted in the United States including 568,668,391 doses of Moderna, based on data from the Moderna global safety database. The study evaluated the risk of myocarditis after vaccination. The observed versus expected rates of myocarditis and myopericarditis within 7 days after mRNA-1273 vaccination (rate ratio) was 0.80 (95% CI, 0.7–0.93) after the first dose, 2.71 (95% CI, 2.4–3.06) after the second dose, and 0.73 (95% CI, 0.59–0.91) after the booster dose. [Straus W, 2022 ]
Corrao G et al. was a retrospective cohort study conducted in Italy that included 9,184,146 vaccine recipients. The study was based on data from the Lombardy Vaccine Integrated Platform and evaluated the risk of myocarditis and pericarditis after vaccination. The adjusted hazard ratio for developing myocarditis was 4.58 (95% CI, 3.32–6.33) after the first dose, 3.54 (95% CI, 2.06–6.08) after the second dose and 5.49 (95% CI, 3.72–8.1) after the booster dose. The adjusted hazard ratio (aHR) for developing pericarditis was 1.59 (95% CI, 1.01–2.51) after the first dose, 2.18 (95% CI, 1.54–3.08) after the second dose and 2.02 (95% CI, 0.28–14.55) after the booster dose. [Corrao G, 2022 ]
Yih W et al was a comparative study conducted in the United States. The aim was to use a tree-based data-mining to assess the safety of the primary series of the three authorized COVID-19 vaccines in the U.S. during 2020–2021: Pfizer-BioNTech, Moderna, and Janssen considering it a screening tool capable of identifying unexpected adverse events. Clusters of local or systemic adverse effects were: urticaria, myalgia, nausea and vomiting, fever, headache, malaise and fatigue, syncope, pain, chills, and unspecified allergy. Most of these clusters began on days 28 or 29, presumably just after the second dose (p=0.0001). There were no clusters of myocarditis/pericarditis, although there was a non-statistically significant grouping of acute myocarditis on days 31–32 and one of acute pericarditis on the same days. [Yih WK, 2022 ]
Yih W et al conducted a comparative study in the United States to evaluate the safety of the first booster doses of the Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273) and Janssen (Ad26.COV2.S) COVID-19 vaccines using a previously described methodology [Yih WK, 2022 ]. The results of cluster screening to identify associations between the vaccine and mRNA booster safety outcomes showed that there were clusters of unspecified adverse effects (p = 0.0001), as well as fever, myalgia, syncope, malaise, and fatigue, headache (all with p = 0.0001), and pain (p = 0.0009), all within the first few days after vaccination. [Katherine Yih W, 2022 ]
Bots et al. was a population-based cohort study with nested self-controlled risk intervals using healthcare data from five European databases to estimate the association between COVID-19 vaccines and myo/pericarditis risk. Over 35 million participants were included and followed between January 2020 to December 2021, of which 54.7% received at least one COVID-19 vaccine dose. The Incidence Rate Ratio (IRR) of myocarditis after the second dose of a Moderna primary schedule was 5.28 (95% CI, 1.68–16.6). IRR of pericarditis after the second dose of a Moderna primary schedule was 1.11 (95% CI, 0.32–3.83). [Bots SH, 2022 ]
Trogstad et al. was a self-controlled case series conducted in Norway including 5,688 women who reported menstrual disturbances within the first six weeks after vaccination through mobile-phone-based questionnaires. 91.6% received two vaccine doses: 2,483 received Pfizer-BioNTech, and 2,736 Moderna. The relative risk of heavy menstrual bleeding was 1.90 (95% CI, 1.69-2.13) after the first dose, and 1.84 (95% CI, 1.66-2.03) after the second dose. [Lill Trogstad, 2022 ]
Hvid A et al. was a cohort study conducted in Denmark, Finland, Norway, and Sweden, including 8,859,339 individuals between 12-39 years old. The incidence rate ratio (IRR) for myocarditis after two doses was 12.56 (95% CI, 9.42-16.73) for males, and 3.82 (95% CI, 1.52-9.6) for females. The IRR after three doses was 6.47 (95% CI, 2.09-20.01) for males. [Anders Hviid, 2022 ]
Xu S et al was a retrospective cohort study conducted in the United States that reported the non-COVID-19 mortality risk following SARS-CoV-2 vaccination, including data from 6,974,817 individuals, from seven Vaccine Safety Datalink sites between December 14th 2020 through August 31st 2021. The adjusted hazard ratios (aHRs) were 0.46 (95% confidence interval [CI], 0.44-0.49) after dose 1 and 0.48 (95% CI, 0.46-0.50) after dose 2 of the BNT162b2 vaccine, 0.41 (95% CI, 0.39-0.44) after dose 1 and 0.38 (95% CI, 0.37-0.40) after dose 2 of the mRNA-1273 vaccine, and 0.55 (95% CI, 0.51-0.59) after receipt of Ad26.COV2.S. [Xu S, 2022 ]
Hanson KE et al was a cohort study conducted in the United States. This study analyzed data from 7,894, 989 vaccinatade individuals: 483,053 with Janssen doses, 8,806,595 with Pfizer doses and 5,830,425 with Moderna doses. The aim was to describe Guillain-Barré Syndrome cases and incidence following COVID-19 vaccinations from December 13, 2020, through November 13, 2021. Unadjusted incidence rate per 100 000 person-years was 32.4 (95% CI, 14.8-61.5) for Jansen vaccine and 1.3 (95% CI, 0.7-2.4) for both mRNA vaccine (aggregated data from Pfizer-BioNTech and Moderna COVID-19 vaccines). Jansen vaccine had an rate ratios of 20.56 (95% CI, 6.94-64.66) compared to mRNA vaccines. [Hanson KE, 2022 ]
Walker JL et al was a self-controlled case series study conducted in United Kingdom that included 7,783,441 participants with the AstraZeneca vaccine, 5,729,152 with the Pfizer vaccine and 255,446 with the Moderna vaccine. This study assessed the association of COVID-19 vaccination with Guillain-Barré Syndrome, transverse myelitis and Bell’s palsy. Incidence rate ratio for Bell’s palsy syndrome was 0.88 (95% CI, 0.32– 2.42). [Walker JL, 2022 ]
Tsang R et al was a self-controlled case series study conducted in England that included 781,200 participants: 300,641 with Pfizer vaccine, 368,898 with AstraZeneca vaccine, 12,024 with Moderna vaccine and 99,637 unvaccinated. The aim was to estimate the incidence of adverse events presenting to primary care following COVID-19 vaccination. Relative incidence of adverse events of interest were 1.20 (95% CI, 1.00-1.44) and 1.13 (95% CI, 0.91-1.39) after the first and second dose of Moderna, respectively. [Tsang RS, 2023 ]
Abara W was a retrospective cohort study conducted in United States that included data from 487,651,785 administered doses: 17,944,515 Janssen, 266,859,784 Pfizer, and 202,847,486 Moderna. The aim was to assess the risk of developing Guillain-Barré Syndrome after COVID-19 vaccination. Guillain-Barré Syndrome was more frequently reported after Janssen than after Pfizer with a reporting rate ratio of 11.40 (95% CI, 8.11-15.99). Guillain-Barré Syndrome was more frequently reported after Janssen than after Moderna with a reporting rate ratio of 9.26 (95% CI, 6.57-13.07). [Abara WE, 2023 ]
Nahab F et al was a retrospective cohort study conducted in the United States that included 4,980,068 participants with at least one dose of SARS-CoV-2 vaccine. The aim was to associate vaccine type and incidence of stroke early after vaccination. 21 days after vaccination the adjusted Odds Ratio for stroke was 1.57 (95% CI, 1.02-2.42) for Ad26.COV2.S vaccine compared to Pfizer, and there was no difference in risk of stroke between Moderna and Pfizer. [Fadi Nahab, 2023 ]
Su WJ et al was a comparative study conducted in Taiwan that included data from 3,566,249 participants with the first and second dose of Moderna and 5,497,108 with the first and second dose of the Pfizer vaccine. This study analyzed nationwide data to determine the risk of developing myocarditis or pericarditis. Crude reporting rate of myocarditis/pericarditis in males and females aged 18 years was 5.80 and 9.62, and 2.36 and 6.31 cases per million vaccines after the first and second doses, respectively. [Su WJ, 2023 ]
Duijster JW was a cohort study conducted in the Netherlands that analyzed data from 27,540 vaccines administered and reported adverse events following immunization over a six month period following vaccination with the Pfizer, AstraZeneca, Moderna or Janssen vaccines. Adjusted Odds Ratio (OR) of any adverse events following immunization after the first dose was 0.37 (95% CI, 0.32-0.41). Adjusted OR of any adverse events following immunization after the second dose was 6.81 (95% CI, 5.99-7.75). [Duijster JW, 2023 ]
Kim HJ et al was a retrospective study conducted in Korea that included data from 6,829 patients with Type 2 Diabetes Mellitus (T2DM) and 20,487 healthy controls. The aim was to assess the risk of severe adverse events after COVID-19 vaccine administration in patients with T2DM. The odds of developing Bell’s palsy, deep vein thrombosis, lymphadenopathy, pulmonary embolism, ischemic stroke and thrombocytopenia were 1.03 (95% CI, 0.60-1.91), 0.44 (95% CI, 0.24-0.87), 3.16 (95% CI, 1.91-5.69), 0.36 (95% CI, 0.21-0.63), 0.38 (95% CI, 0.17-0.94) and 0.24 (95% CI, 0.10-0.60), respectively, for the Pfizer vaccine (having the Janssen vaccine as reference). The odds of developing Bell’s palsy, deep vein thrombosis, lymphadenopathy, pulmonary embolism, ischemic stroke and thrombocytopenia were 1.14 (95% CI, 0.67-2.10), 0.38 (95% CI, 0.21-0.73), 2.24 (95% CI, 1.36-4.05), 0.50 (95% CI, 0.31-0.85), 0.43 (95% CI, 0.21-1.02) and 0.38 (95% CI, 0.18-0.88), respectively, for the Moderna vaccine (having the Janssen vaccine as reference). [Kim HJ, 2023 ]
Non-comparative studies
Pawlowsky C et al. conducted a non-comparative study in the United States, which included 266,094 participants. The frequencies of cerebral venous sinus thrombosis (CVST) observed among people who received FDA-cleared COVID-19 vaccines from Pfizer-BioNTech (n = 94,818 doses), Moderna (n = 36,350 doses), and Johnson & Johnson were studied. Johnson - J&J (n = 1,745 doses), and among people who received one of the 10 FDA-approved non-COVID-19 vaccines (n = 771,805 doses). When comparing CVST incidence rates in 30-day time windows before and after vaccination, no statistically significant differences were found for COVID-19 vaccines or any other vaccine studied in this population. In total, 3 cases of CVST were observed within 30 days of vaccination with Pfizer-BioNTech (2 female, 1 male; Ages (years): [79, 80, 84]), including one individual with a history of thrombosis and another individual with recent trauma in the past 30 days. No cases of CVST are believed among patients who received the Moderna or J&J vaccines in this study population. Overall, this real-world evidence-based study highlights that TSVC is rare and not significantly associated with the COVID-19 vaccine [Pawlowski C, 2021 ].
Pushkar A conducted a non-comparative study in the United States, in which he reported 68,123 adverse events (Pfizer, Moderna or Janssen vaccines). A statistically significant signal was found between cerebrovascular accidents (CVA) events and each of the three COVID-19 vaccines (Pfizer/BioNTech's, Moderna's, and Janssen's) in the vaccine adverse event reporting system (VAERS). Women and people 65 and older had a higher number of case reports of stroke events with COVID-19 vaccines. Women also had more reports of COVID-19 adverse events in which stroke was reported and resulted in the patient having permanent disability or death [Pushkar Aggarwal, 2021 ].
Zhao H et al. was a cross-sectional conducted in the United States. The study enrolled 15,785 adverse event reports (0.7% (113) urologic symptoms) from participants that received Pfizer-BioNTech and Moderna vaccines. Based on data from the FDA vaccine Adverse Event Reporting System (VAERS) as of February 12th, 2021 [Zhao H., 2021 ].
Schulz JB et al. was a non-comparative study carried out in Germany, which included 7,126,424 first doses (Pfizer-BioNTech, Moderna, AstraZeneca vaccines). The study aimed to estimate the incidence of cerebral sinus and venous thrombosis (CVT) within 1 month from first dose administration and the frequency of vaccine-induced immune thrombotic thrombocytopenia (VITT) as the underlying mechanism after vaccination. All reported cases occurred after vaccination with ChAdOx1 (85.5%) and BNT162b2 (14.5%). No cases were reported with mRNA-1273.[Schulz JB, 2021 ]
Presby D et al. is a retrospective cohort conducted in the United States. The study enrolled 50,977 (AstraZeneca (AZ, n=2,093), Janssen/Johnson & Johnson (J&J&J, n=3,888), Moderna (n=23,776; M1, 14,553 first dose; M2, 9,223 second dose), or Pfizer/BioNTech (n=35,929; P&B1, 22,387 first dose; P&B2, 13,542 second dose) participants. Based on data from subscribers to the WHOOP platform using data collected through April 14, 2021. [David Presby, 2021 ].
Gee j et al. conducted a non-comparative study in the United States, which included 1,602,065 vaccine recipients (Moderna or Pfizer). 814,648 (50.8%) received Pfizer-BioNTech and 787,417 (49.2%) received Moderna vaccines. The requested local and systemic reactions were similar among people who received the first doses of the Pfizer-BioNTech and Moderna vaccines. Injection site pain, fatigue, headache, myalgia, and chills were reported more frequently. Members reported more reactions on the day after vaccination than on any other day. [Gee J, 2021 ].
Shimabukuro T et al. (CDC Report) was a retrospective cohort study conducted in the United States. The study enrolled 35,691 (Moderna or Pfizer vaccines) pregnant women who received the Moderna or Pfizer COVID-19 vaccine. Although not directly comparable, the calculated proportions of adverse pregnancies and neonatal outcomes in people vaccinated against COVID-19 who had a full pregnancy were similar to the incidences reported in studies with pregnant women that were conducted before the COVID-19 pandemic. Among the 221 pregnancy-related adverse events reported to Vaccine Adverse Event Reporting System (VAERS), the most frequently reported event was miscarriage (46 cases) [Shimabukuro TT, 2021 ].
Abbattista M et al. conducted a non-comparative study in Europe, which included 748,248 reports of adverse drug reactions (Pfizer-BioNTech, Janssen, Moderna and AstraZeneca vaccines). The notification rate of cerebral venous thrombosis (CVT) per 1 million vaccinated persons-days was 1.92 (95% CI, 1.71-2.12) for Pfizer-BioNTech, 5.63 (95% CI, 4, 74-6.64) for Moderna, 21.60 (95% CI, 20.16-23.11) for AstraZeneca and 11.48 (95% CI, 9.57-13, 67) for Janssen. CVT occurred in conjunction with thrombocytopenia for all four vaccines. The observed-to-expected (OE) analysis ratio was greater than one for all four vaccines, both with the lowest and highest background incidence of CVT. [Abbattista M, 2021 ].
Naim Ouldali et al. was a non-comparative study conducted in France. The study enrolled 4,079,234 12-17-year-old children and assessed the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children using the French enhanced pharmacovigilance surveillance system for COVID-19 vaccines [Naim Ouldali, 2022 ].
Oster ME et al was a non-comparative study conducted in the United States. The study enrolled 192,405,448 persons aged 12 year or older receiving a total of 354,100,845 mRNA-based COVID-19 vaccines between December 2020 and August 2021, using data from the Vaccine Adverse Event Reporting System (VAERS) with the objective of describing reports of myocarditis and reporting rates after mRNA-based COVID-19 vaccination in the US. [Oster ME, 2022 ]
Kitagawa H et al was a non-comparative study conducted in Japan. The study enrolled 12,214 participants receiving Pfizer or Moderna COVID-19 vaccines and reporting adverse reactions an online survey of self-reported adverse reactions after mass vaccination. The study results showed that adverse reactions were more frequently reported in females, younger individuals, and after the mRNA-1273 vaccine [Kitagawa H, 2022 ].
Rolfes L et al. was a cohort study conducted in the Netherlands. The study enrolled 22,184 participants and explored factors that were associated with reactogenicity in general and systemic after the first dose of COVID-19 vaccine through a web-based design using patient reported outcomes between February 1st 2021 and May 9th 2021 [Rolfes L, 2022 ].
Marco Massari et al. was a self-controlled case series study conducted in Italy. The study included 2,861,809 participants and investigated the association between SARS-CoV-2 mRNA vaccines and myocarditis/pericarditis, using national data on COVID-19 vaccination and emergency care/hospital admissions. The study reported 441 participants aged 12-39 years developing myocarditis/pericarditis (346 received Pfizer COVID-19 vaccine and 95 received Moderna COVID-19 vaccine)[Marco Massari, 2022 ].
Kant A et al. was a non-comparative study conducted in the Netherlands. The study included 27,554 participants and assessed systemic adverse events following immunization and adverse events of special interest following immunization for Pfizer-BioNTech, Moderna, Janssen and AstraZeneca vaccines [Kant A, 2022 ].
Nguyen S et al. was a observational, cross-sectional, pharmacovigilance cohort study that examined individual case safety reports from VigiBase®, the World Health Organization’s pharmacovigilance database. The study aimed to identify cases of tranverse myelitis (TM) following SARS-CoV-2 vaccination with Pfizer/BioNTech, Moderna, Oxford–AstraZeneca and Novavax vaccines. The study results showed that 6,921,165 adverse events were reported, with 818 reports correspoding to TM. 84 (17%) of the cases were related to the Moderna vaccine. [Nguyen S, 2022 ].
Toledo-Salinas et al. conducted a nationwide observational study among recipients of 61,414,803 doses of seven different COVID-19 vaccines, between December 2020 - October 2021 in Mexico, to identify the observed incidence of anaphylaxis in recipients of different anti-SARS-CoV-2 vaccines. Unadjusted incidence of anaphylaxis per million doses administered was 5.28 (95% CI 2.42–11.52) for mRNA-1273. [Toledo-Salinas C, 2022 ]
Mascolo A et al. conducted an observational study to investigate the adverse events following immunization (AEFI) with COVID-19 vaccines during pregnancy from the EudraVigilance database. The study included 1,315,315 Individual Case Safety Reports from the European Union for the year 2021, of which 3,252 reports were related to COVID-19 vaccines during pregnancy. 967 persons received the Moderna vaccine. The most reported AEFI (54.91%) were non-pregnancy-specific adverse events. Among pregnancy-specific adverse events, the most frequent was the termination of pregnancy and risk of abortion. [Mascolo A, 2022 ]
García-Grimshaw M was a non-comparative study conducted in Mexico that reported the incidence of Guillain-Barré syndrome (GBS) following COVID-19 vaccination. The study informed the adverse events of 81,842,426 first or second doses of seven COVID-19 vaccines (Coronavac, Moderna, Pfizer, AstraZeneca, Sputnik V, CanSino, and Janssen), with 2,318,057 doses corresponding to the Moderna vaccine. 97 cases of GBS were identified through passive epidemiological surveillance, 3 of them related to the Moderna vaccination, with an unadjusted incidence of 1.29 (95% CI 0.44-3.81) per million doses administered. [García-Grimshaw M, 2022 ]
Naveed Z was a study conducted in Canada, including 3,095,414 individuals receiving 2 doses of mRNA vaccines: 2,223,454 received Pfizer and 871,960 received Moderna. The study assessed the risk of developing myocarditis, pericarditis and myopericarditis after COVID-19 mRNA vaccination. The rate per million doses for myocarditis, pericarditis and myopericarditis 21 days after the second dose was 35.55 (95% CI, 24.15-50.46), 22.93 (95% CI, 14.01-35.42) and 56.20 (95% CI, 41.58-74.30), respectively. [Naveed Z, 2022 ]
Naveed Z was a study conducted in Canada, including 10,255,385 doses of mRNA vaccines: 6,989,921 doses of BNT162b2 and 3,265,464 doses of mRNA-1273. The study assessed the risk of developing myocarditis after COVID-19 vaccination. The overall rate of myocarditis per 100,000 was 1.44 (95% CI, 1.06–1.91) for Moderna vaccine doses using a 7-day risk window, using a 21-day risk window the rate was 1.75 (95% CI, 1.32–2.26) for Pfizer vaccines. [8ba679dcd2ecc509a1a8dad29a49fc443bd9190]
Yih WK et al was comparative study conducted in United States. The aim was to use a tree-based data-mining to assess the safety of the primary series of the three authorized or approved COVID-19 vaccines in the U.S. during 2020–2021, Pfizer-BioNTech, Moderna, and Janssen, considering it a screening tool capable of identifying unexpected adverse events. Clusters of local or systemic adverse effects were urticaria, myalgia, nausea and vomiting, fever, headache, malaise and fatigue, syncope, pain, chills, and unspecified allergy. Most of these clusters began on days 28 or 29, presumably just after dose 2 (p=0.0001). There were no clusters of myocarditis/pericarditis, although there was a non-statistically significant grouping of acute myocarditis in days 31–32 and one of acute pericarditis also in days 31–32. [Yih WK, 2022 ]
Jacobs JW et al was a surveillance study conducted in the United States that reported autoimmune haemolytic anemia and immune thrombocytopenia following SARS-CoV-2 and non-SARS-CoV-2 vaccination, including 863 reports between 1990 and 2022. There were 26 cases of autoimmune haemolytic anemia and 126 cases of immune thrombocytopenia associated with the Moderna vaccine. [Jacobs JW, 2022 ]
Gallo AT et al was a non comparative study conducted in Australia that included 977,559 participants with Pfizer, AstraZeneca, Moderna and Novavax vaccine: 513,974 participants with Moderna vaccine, 161,857 with AstraZeneca vaccine, 258,606 with Pfizer vaccine and 11,967 with Novavax vaccine. 9 cases of anaphylactic reaction were reported after the first Moderna dose (0,01%), 1 case after the second dose (0,00%) and 5 cases after the third dose (0,00%). After the first dose of AstraZeneca 6 cases were reported for anaphylactic reactions (0,01%) and 1 case after the second dose (0,00%). After the first dose of Pfizer there were 0 cases of anaphylactic reactions, 1 case after the second dose and 0 cases after the third dose. No cases of anaphylaxis associated with the Novavax vaccine have been reported. [Gallo AT, 2022 ]
Xu S et al was a retrospective cohort study conducted in the United States that reported the non-COVID-19 mortality risk following SARS-CoV-2 vaccination, including data from 6,974,817 individuals, from seven Vaccine Safety Datalink sites between December 14th 2020 through August 31st 2021. The adjusted hazard ratios after Moderna were 0.41 (95% CI, 0.39–0.44) after dose one and 0.38 (95% CI, 0.37–0.40) after dose two. [Xu S, 2022 ]
Kajiwara S et al was a cross sectional study conducted in Japan that included 55 students (18-22 years) and the majority received Moderna vaccine (91%). The rest of the participants received the Pfizer vaccine. The aim was to investigate the effect of COVID-19 vaccines on the menstrual cycle. The difference between the predicted and actual menstrual cycle length was 1.9 ± 3.0, 1.6 ± 2.8 (p value = 0.557), and 2.5 ± 3.8 (p value = 0.219) days before vaccination and after the first and second dose of the vaccine, respectively. [Kajiwara S, 2023 ]
Monitoring
WHO indicates that after a vaccine is approved for use, regulators conduct robust monitoring of efficacy, as well as monitoring of safety and risk minimization (pharmacovigilance) activities. They need to continually monitor the safety of the vaccine to ensure that the benefits of the vaccine continue to outweigh the risks. [WHO, 2022 ]
Regarding safety surveillance and monitoring, serious adverse events, anaphylaxis and other severe allergic reactions, Bell's palsy, cases of multisystem inflammatory syndrome, cases of COVID-19 after vaccination resulting in hospitalization or death should be identified and recorded.
Regarding the effectiveness of the vaccine, the following should be monitored:
− Efficacy of the vaccine over time and whether protection can be prolonged with booster doses.
− Studies to investigate whether this vaccine reduces the transmission and viral spread of SARS-CoV-2.
− Evaluation and notification of vaccine failures and information on viral sequences.
Regarding the subgroups of interest
− Prospective studies on the safety of the COVID-19 vaccine in pregnant and lactating females.
− Occasional controlled trials on the safety and security of vaccination in children under 18 years of age.
− Safety data from vaccination in immunosuppressed people, including patients living with HIV and autoimmune diseases.
To review more information on the topic [WHO, 2022 ],[World Health Organization, 2021 ], [Organización Mundial de la Salud, 2022 ]
References
[WHO, 2021] WHO. WHO recommendation Moderna COVID-19 mRNA Vaccine (nucleoside modified). 2021; WHO. WHO recommendation Moderna COVID-19 mRNA Vaccine (nucleoside modified). 2021;
[WHO, 2022] WHO. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19. 2022; WHO. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19. 2022;
[EMA , 2021] EMA. EMA recommends COVID-19 Vaccine Moderna for authorisation in the EU. Press release - European Medicines Agency - 6 January 2021. 2021; EMA. EMA recommends COVID-19 Vaccine Moderna for authorisation in the EU. Press release - European Medicines Agency - 6 January 2021. 2021;
[EMA, 2021] EMA. COVID-19 vaccine Spikevax approved for children aged 12 to 17 in EU. 2021; EMA. COVID-19 vaccine Spikevax approved for children aged 12 to 17 in EU. 2021;
[EMA, 2022] EMA. EMA recommends approval of Spikevax for children aged 6 to 11. 2022; EMA. EMA recommends approval of Spikevax for children aged 6 to 11. 2022;
[MINISTERIO DE SALUD DE ARGENTINA, 2021] MINISTERIO DE SALUD DE ARGENTINA. Resolución 2711/2021 RESOL-2021-2711-APN-MS. 2021;
[Government of Canada, 2022] Government of Canada. Moderna Spikevax COVID-19 vaccine. 2022; Government of Canada. Moderna Spikevax COVID-19 vaccine. 2022;
[Instituto de Salud Pública de Chile, 2022] Instituto de Salud Pública de Chile. Vacunas Covid-19. 2022; Instituto de Salud Pública de Chile. Vacunas Covid-19. 2022;
[Instituo de Salud Pública, 2022] Instituo de Salud Pública. ISP amplía rango etario desde los seis meses de edad para vacunas contra COVID-19. 2022;
[INVIMA, 2021] INVIMA. Invima otorgó Autorización Sanitaria de Uso de Emergencia a la vacuna desarrollada por la farmacéutica Moderna Switzerland GmbH. Press release. 2021; INVIMA. Invima otorgó Autorización Sanitaria de Uso de Emergencia a la vacuna desarrollada por la farmacéutica Moderna Switzerland GmbH. Press release. 2021;
[INVIMA, 2021] INVIMA. Personas a partir de los 12 años podrán recibir la vacuna desarrollada por la farmacéutica Moderna Switzerland GmbH contra covid-19. Press release. 2021; INVIMA. Personas a partir de los 12 años podrán recibir la vacuna desarrollada por la farmacéutica Moderna Switzerland GmbH contra covid-19. Press release. 2021;
[FDA, 2022] FDA. Spikevax and Moderna COVID-19 Vaccine. 2022; FDA. Spikevax and Moderna COVID-19 Vaccine. 2022;
[FDA, 2022] FDA. Moderna COVID-19 Vaccine Regulatory Information. 2022; FDA. Moderna COVID-19 Vaccine Regulatory Information. 2022;
[Gobierno de México, 2021] Gobierno de México. COFEPRIS issues authorization for emergency use of Moderna vaccine. Press release - COFEPRIS - 18 de agosto de 2021. 2021; Gobierno de México. COFEPRIS issues authorization for emergency use of Moderna vaccine. Press release - COFEPRIS - 18 de agosto de 2021. 2021;
[EMA, 2022] EMA. Spikevax (previously COVID-19 Vaccine Moderna). 2022; EMA. Spikevax (previously COVID-19 Vaccine Moderna). 2022;
[Health Canada, 2022] Health Canada. Health Canada authorizes first bivalent COVID-19 booster for adults 18 years and older. 2022; Health Canada. Health Canada authorizes first bivalent COVID-19 booster for adults 18 years and older. 2022;
[ISP, 2022] ISP. ISP aprueba uso de emergencia de vacunas bivalentes de laboratorios Pfizer y Moderna. 2022; ISP. ISP aprueba uso de emergencia de vacunas bivalentes de laboratorios Pfizer y Moderna. 2022;
[Health Canada, 2022] Health Canada. Health Canada authorizes second bivalent COVID-19 booster targeting the Omicron BA.4/5 variants. 2022; Health Canada. Health Canada authorizes second bivalent COVID-19 booster targeting the Omicron BA.4/5 variants. 2022;
[World Health Organization, 2020] World Health Organization. WHO recommendation ModernaTX, Inc/USFDA COVID-19 mRNA vaccine (nucleoside modified). 2020; World Health Organization. WHO recommendation ModernaTX, Inc/USFDA COVID-19 mRNA vaccine (nucleoside modified). 2020;
[MODERNA TX INC. & LONZA SALES LTD, 2020] MODERNA TX INC. & LONZA SALES LTD.. GLOBAL LONG TERM AGREEMENT. Effective Date May 1, 2020 - Exhibit at U.S. Securities and Exchange Commission. 2020; MODERNA TX INC. & LONZA SALES LTD.. GLOBAL LONG TERM AGREEMENT. Effective Date May 1, 2020 - Exhibit at U.S. Securities and Exchange Commission. 2020;
[Rick Mullin, 2021] Rick Mullin. Pfizer, Moderna ready vaccine manufacturing networks. Chemical & Engineering News - NOVEMBER 25, 2020. 2021;98(46).
[Wrapp D, 2020] Wrapp D, Wang N, Corbett KS et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (New York, N.Y.). 2020;367(6483):1260-1263. Wrapp D, Wang N, Corbett KS et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (New York, N.Y.). 2020;367(6483):1260-1263.
[Corbett KS, 2020] Corbett KS, Edwards DK, Leist SR et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature. 2020;586(7830):567-571. Corbett KS, Edwards DK, Leist SR et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature. 2020;586(7830):567-571.
[Xia X, 2021] Xia X. Domains and Functions of Spike Protein in Sars-Cov-2 in the Context of Vaccine Design. Viruses. 2021;13(1). Xia X. Domains and Functions of Spike Protein in Sars-Cov-2 in the Context of Vaccine Design. Viruses. 2021;13(1).
[Hsieh CL, 2020] Hsieh CL, Goldsmith JA, Schaub JM et al. Structure-based design of prefusion-stabilized SARS-CoV-2 spikes. Science (New York, N.Y.). 2020;369(6509):1501-1505. Hsieh CL, Goldsmith JA, Schaub JM et al. Structure-based design of prefusion-stabilized SARS-CoV-2 spikes. Science (New York, N.Y.). 2020;369(6509):1501-1505.
[Karikó K, 2008] Karikó K, Muramatsu H, Welsh FA et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Molecular therapy : the journal of the American Society of Gene Therapy. Karikó K, Muramatsu H, Welsh FA et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Molecular therapy : the journal of the American Society of Gene Therapy.
[Schlake T, 2012] Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ. Developing mRNA-vaccine technologies. RNA biology. 2012;9(11):1319-30. Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ. Developing mRNA-vaccine technologies. RNA biology. 2012;9(11):1319-30.
[Hassett KJ, 2019] Hassett KJ, Benenato KE, Jacquinet E et al. Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines. Molecular therapy. Nucleic acids. 2019;15:1-11. Hassett KJ, Benenato KE, Jacquinet E et al. Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines. Molecular therapy. Nucleic acids. 2019;15:1-11.
[Stenler S, 2014] Stenler S, Blomberg P, Smith CI. Safety and efficacy of DNA vaccines: plasmids vs. minicircles. Human vaccines & immunotherapeutics. 2014;10(5):1306-8. Stenler S, Blomberg P, Smith CI. Safety and efficacy of DNA vaccines: plasmids vs. minicircles. Human vaccines & immunotherapeutics. 2014;10(5):1306-8.
[GAVI,2020] GAVI. Will an mRNA vaccine alter my DNA?. Vaccine work. 2020; GAVI. Will an mRNA vaccine alter my DNA?. Vaccine work. 2020;
[Pardi N, 2018] Pardi N, Hogan MJ, Porter FW et al. mRNA vaccines - a new era in vaccinology. Nature reviews. Drug discovery. 2018;17(4):261-279. Pardi N, Hogan MJ, Porter FW et al. mRNA vaccines - a new era in vaccinology. Nature reviews. Drug discovery. 2018;17(4):261-279.
[Liu MA, 2019] Liu MA. A Comparison of Plasmid DNA and mRNA as Vaccine Technologies. Vaccines. 2019;7(2). Liu MA. A Comparison of Plasmid DNA and mRNA as Vaccine Technologies. Vaccines. 2019;7(2).
[Pepini T, 2017] Pepini T, Pulichino AM, Carsillo T et al. Induction of an IFN-Mediated Antiviral Response by a Self-Amplifying RNA Vaccine: Implications for Vaccine Design. Journal of immunology (Baltimore, Md. : 1950). 2017;198(10):4012-4024. Pepini T, Pulichino AM, Carsillo T et al. Induction of an IFN-Mediated Antiviral Response by a Self-Amplifying RNA Vaccine: Implications for Vaccine Design. Journal of immunology (Baltimore, Md. : 1950). 2017;198(10):4012-4024.
[Stone CA, 2019] Stone CA, Rukasin CRF, Beachkofsky TM et al. Immune Mediated Adverse Reactions to Vaccines. British journal of clinical pharmacology. 2019;85(12):2694-2706. Stone CA, Rukasin CRF, Beachkofsky TM et al. Immune Mediated Adverse Reactions to Vaccines. British journal of clinical pharmacology. 2019;85(12):2694-2706.
[Stone CA, 2019] Stone CA, Liu Y, Relling MV et al. Immediate Hypersensitivity to Polyethylene Glycols and Polysorbates: More Common Than We Have Recognized. The journal of allergy and clinical immunology. In practice. 2019;7(5):1533-1540.e8. Stone CA, Liu Y, Relling MV et al. Immediate Hypersensitivity to Polyethylene Glycols and Polysorbates: More Common Than We Have Recognized. The journal of allergy and clinical immunology. In practice. 2019;7(5):1533-1540.e8.
[EMA, 2022] EMA. ECDC and EMA update recommendations on additional booster doses of mRNA COVID-19 vaccines. 2022; EMA. ECDC and EMA update recommendations on additional booster doses of mRNA COVID-19 vaccines. 2022;
[WHO, 2022] WHO. WHO SAGE Roadmap for prioritizing uses of COVID-19 vaccines. 2022; WHO. WHO SAGE Roadmap for prioritizing uses of COVID-19 vaccines. 2022;
[Moderna Inc., 2020] Moderna Inc.. Moderna Announces Longer Shelf Life for its COVID-19 Vaccine Candidate at Refrigerated Temperatures. Press release - Moderna - November 16, 2020 at 6:52 AM EST. 2020; Moderna Inc.. Moderna Announces Longer Shelf Life for its COVID-19 Vaccine Candidate at Refrigerated Temperatures. Press release - Moderna - November 16, 2020 at 6:52 AM EST. 2020;
[WHO, 2021] WHO. COVID-19 vaccination: supply and logistics guidance: interim guidance, 12 February 2021. WHO/2019-nCoV/vaccine_deployment/logistics/2021.1. 2021; WHO. COVID-19 vaccination: supply and logistics guidance: interim guidance, 12 February 2021. WHO/2019-nCoV/vaccine_deployment/logistics/2021.1. 2021;
[National Institute of Allergy and Infectious Diseases (NIAID), 2020] National Institute of Allergy and Infectious Diseases (NIAID). Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) to Prevent SARS-CoV-2 Infection. clinicaltrials.gov. 2020; National Institute of Allergy and Infectious Diseases (NIAID). Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) to Prevent SARS-CoV-2 Infection. clinicaltrials.gov. 2020;
[Jackson LA, 2020] Jackson LA, Anderson EJ, Rouphael NG et al. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. The New England journal of medicine. 2020;383(20):1920-1931. Jackson LA, Anderson EJ, Rouphael NG et al. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. The New England journal of medicine. 2020;383(20):1920-1931.
[Widge AT, 2021] Widge AT, Rouphael NG, Jackson LA et al. Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination. The New England journal of medicine. 2021;384(1):80-82. Widge AT, Rouphael NG, Jackson LA et al. Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination. The New England journal of medicine. 2021;384(1):80-82.
[Greaney AJ, 2021] Greaney AJ, Loes AN, Gentles LE et al. Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection. Science translational medicine. 2021;13(600). Greaney AJ, Loes AN, Gentles LE et al. Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection. Science translational medicine. 2021;13(600).
[Kai Wu, 2021] Kai Wu, Anne P. Werner, Matthew Koch et al. Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine - Preliminary Report. The New England Journal of Medicine. 2021; Kai Wu, Anne P. Werner, Matthew Koch et al. Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine - Preliminary Report. The New England Journal of Medicine. 2021;
[Anderson EJ, 2020] Anderson EJ, Rouphael NG, Widge AT et al. Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. The New England journal of medicine. 2020;383(25):2427-2438. Anderson EJ, Rouphael NG, Widge AT et al. Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. The New England journal of medicine. 2020;383(25):2427-2438.
[National Institute of Allergy and Infectious Diseases (NIAID), 2021] National Institute of Allergy and Infectious Diseases (NIAID). Safety and Immunogenicity Study of a SARS-CoV-2 (COVID-19) Variant Vaccine (mRNA-1273.351) in Naïve and Previously Vaccinated Adults. clinicaltrials.gov. 2021; National Institute of Allergy and Infectious Diseases (NIAID). Safety and Immunogenicity Study of a SARS-CoV-2 (COVID-19) Variant Vaccine (mRNA-1273.351) in Naïve and Previously Vaccinated Adults. clinicaltrials.gov. 2021;
[Anderson E, 2022] Anderson E, Jackson L, Rouphael N et al. Safety and Immunogenicity of a Third Dose of SARS-CoV-2 mRNA Vaccine — An Interim Analysis. ResearchSquare. 2022; Anderson E, Jackson L, Rouphael N et al. Safety and Immunogenicity of a Third Dose of SARS-CoV-2 mRNA Vaccine — An Interim Analysis. ResearchSquare. 2022;
[Chang Gung Memorial Hospital, 2021] Chang Gung Memorial Hospital. The Immune Response of Heterologous Boost Third Dose of mRNA and Protein COVID-19 Vaccine: a Single-blind, and Randomized Study. clinicaltrials.gov. 2021; Chang Gung Memorial Hospital. The Immune Response of Heterologous Boost Third Dose of mRNA and Protein COVID-19 Vaccine: a Single-blind, and Randomized Study. clinicaltrials.gov. 2021;
[Chih-Hsien Chuang, 2022] Chih-Hsien Chuang, Chung-Guei Huang, Ching-Tai Huang et al. Titers and capacity of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: a single-blinded Chih-Hsien Chuang, Chung-Guei Huang, Ching-Tai Huang et al. Titers and capacity of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: a single-blinded
[National Institute of Allergy and Infectious Diseases (NIAID), 2022] National Institute of Allergy and Infectious Diseases (NIAID). COVID-19 Variant Immunologic Landscape Trial (COVAIL Trial). clinicaltrials.gov. 2022; National Institute of Allergy and Infectious Diseases (NIAID). COVID-19 Variant Immunologic Landscape Trial (COVAIL Trial). clinicaltrials.gov. 2022;
[Angela R Branche, 2022] Angela R Branche, Nadine G Rouphael, David D Diemert et al. SARS-CoV-2 Variant Vaccine Boosters Trial: Preliminary Analyses. medRxiv. 2022; Angela R Branche, Nadine G Rouphael, David D Diemert et al. SARS-CoV-2 Variant Vaccine Boosters Trial: Preliminary Analyses. medRxiv. 2022;
[ModernaTX, Inc., 2020] ModernaTX, Inc.. Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 COVID-19 Vaccine in Adults Aged 18 Years and Older. clinicaltrials.gov. 2020; ModernaTX, Inc.. Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 COVID-19 Vaccine in Adults Aged 18 Years and Older. clinicaltrials.gov. 2020;
[Chu L, 2021] Chu L, McPhee R, Huang W et al. A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine. Vaccine. 2021;39(20):2791-2799. Chu L, McPhee R, Huang W et al. A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine. Vaccine. 2021;39(20):2791-2799.
[University Hospital Southampton NHS Foundation Trust, 2021] University Hospital Southampton NHS Foundation Trust. Evaluating COVID-19 Vaccination Boosters. ISRCTN registry. 2021; University Hospital Southampton NHS Foundation Trust. Evaluating COVID-19 Vaccination Boosters. ISRCTN registry. 2021;
[Munro, Alasdair P S, 2021] Munro, Alasdair P S, Janani, Leila, Cornelius, Victoria et al. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, con Munro, Alasdair P S, Janani, Leila, Cornelius, Victoria et al. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, con
[Munro APS, 2022] Munro APS, Feng S, Janani L et al. Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicen Munro APS, Feng S, Janani L et al. Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicen
[Liu X, 2022] Liu X, Munro APS, Feng S et al. Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: three month analyses of the COV-BOOST trial. The Journal of infection. 2 Liu X, Munro APS, Feng S et al. Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: three month analyses of the COV-BOOST trial. The Journal of infection. 2
[Medical University of Vienna, 2021] Medical University of Vienna. A Randomized, Parallel Group, Single-Blind, Phase 2 Study to Evaluate the immune response of two classes of SARS-CoV-2 Vaccines (COVID-19) employed as Second Boost in Patients under current Rituximab Therapy and no humoral re Medical University of Vienna. A Randomized, Parallel Group, Single-Blind, Phase 2 Study to Evaluate the immune response of two classes of SARS-CoV-2 Vaccines (COVID-19) employed as Second Boost in Patients under current Rituximab Therapy and no humoral re
[Michael Bonelli, 2021] Michael Bonelli, Daniel Mrak, Selma Tobudic et al. Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial. medRxiv Michael Bonelli, Daniel Mrak, Selma Tobudic et al. Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial. medRxiv
[Bonelli M, 2022] Bonelli M, Mrak D, Tobudic S et al. Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomised controlled trial. Annals of the rheumati Bonelli M, Mrak D, Tobudic S et al. Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomised controlled trial. Annals of the rheumati
[Janssen Vaccines & Prevention B.V., 2020] Janssen Vaccines & Prevention B.V.. A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults. clinicaltrials.gov. 2020; Janssen Vaccines & Prevention B.V.. A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults. clinicaltrials.gov. 2020;
[Heinzel A, 2022] Heinzel A, Schretzenmeier E, Regele F et al. Three-Month Follow-Up of Heterologous vs. Homologous Third SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Secondary Analysis of a Randomized Controlled Trial. Frontiers in medicine. 2022;9:936126. Heinzel A, Schretzenmeier E, Regele F et al. Three-Month Follow-Up of Heterologous vs. Homologous Third SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Secondary Analysis of a Randomized Controlled Trial. Frontiers in medicine. 2022;9:936126.
[Reindl-Schwaighofer R, 2021] Reindl-Schwaighofer R, Heinzel A, Mayrdorfer M et al. Comparison of SARS-CoV-2 Antibody Response 4 Weeks After Homologous vs Heterologous Third Vaccine Dose in Kidney Transplant Recipients: A Randomized Clinical Trial. JAMA internal medicine. 2021; Reindl-Schwaighofer R, Heinzel A, Mayrdorfer M et al. Comparison of SARS-CoV-2 Antibody Response 4 Weeks After Homologous vs Heterologous Third Vaccine Dose in Kidney Transplant Recipients: A Randomized Clinical Trial. JAMA internal medicine. 2021;
[ModernaTX, Inc., 2020] ModernaTX, Inc.. A Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 Vaccine in Adolescents 12 to <18 Years Old to Prevent COVID-19. clinicaltrials.gov. 2020; ModernaTX, Inc.. A Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 Vaccine in Adolescents 12 to <18 Years Old to Prevent COVID-19. clinicaltrials.gov. 2020;
[Ali K, 2021] Ali K, Berman G, Zhou H et al. Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents. The New England journal of medicine. 2021; Ali K, Berman G, Zhou H et al. Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents. The New England journal of medicine. 2021;
[ModernaTX, Inc., 2021] ModernaTX, Inc.. A Study to Evaluate Safety and Effectiveness of mRNA-1273 Vaccine in Healthy Children Between 6 Months of Age and Less Than 12 Years of Age. clinicaltrials.gov. 2021; ModernaTX, Inc.. A Study to Evaluate Safety and Effectiveness of mRNA-1273 Vaccine in Healthy Children Between 6 Months of Age and Less Than 12 Years of Age. clinicaltrials.gov. 2021;
[Creech CB, 2022] Creech CB, Anderson E, Berthaud V et al. Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age. The New England journal of medicine. 2022;386(21):2011-2023. Creech CB, Anderson E, Berthaud V et al. Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age. The New England journal of medicine. 2022;386(21):2011-2023.
[Anderson EJ, 2022] Anderson EJ, Creech CB, Berthaud V et al. Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age. The New England journal of medicine. 2022; Anderson EJ, Creech CB, Berthaud V et al. Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age. The New England journal of medicine. 2022;
[ModernaTX, Inc., 2021] ModernaTX, Inc.. A Study to Evaluate the Immunogenicity and Safety of mRNA-1273.211 Vaccine for COVID-19 Variants. clinicaltrials.gov. 2021; ModernaTX, Inc.. A Study to Evaluate the Immunogenicity and Safety of mRNA-1273.211 Vaccine for COVID-19 Variants. clinicaltrials.gov. 2021;
[Chalkias S, 2022] Chalkias S, Harper C, Vrbicky K et al. A Bivalent Omicron-Containing Booster Vaccine against Covid-19. The New England journal of medicine. 2022; Chalkias S, Harper C, Vrbicky K et al. A Bivalent Omicron-Containing Booster Vaccine against Covid-19. The New England journal of medicine. 2022;
[Chalkias S, 2022] Chalkias S, Eder F, Essink B et al. Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial. Nature medicine. 2022; Chalkias S, Eder F, Essink B et al. Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial. Nature medicine. 2022;
[Spyros Chalkias, 2022] Spyros Chalkias, Jordan Whatley, Frank Eder et al. Safety and Immunogenicity of an Omicron BA.4/BA.5 Bivalent Vaccine against Covid-19. medRxiv. 2022; Spyros Chalkias, Jordan Whatley, Frank Eder et al. Safety and Immunogenicity of an Omicron BA.4/BA.5 Bivalent Vaccine against Covid-19. medRxiv. 2022;
[ModernaTX, Inc., 2022] ModernaTX, Inc.. A Study to Evaluate the Immunogenicity and Safety of mRNA-1273.529 Vaccine for the COVID-19 Omicron Variant B.1.1.529. clinicaltrials.gov. 2022; ModernaTX, Inc.. A Study to Evaluate the Immunogenicity and Safety of mRNA-1273.529 Vaccine for the COVID-19 Omicron Variant B.1.1.529. clinicaltrials.gov. 2022;
[Lee, I. T., 2023] Lee, I. T., Cosgrove, C. A., Moore, P. et al. A Randomized Trial Comparing Omicron-Containing Boosters with the Original Covid-19 Vaccine mRNA-1273. medRxiv. 2023; Lee, I. T., Cosgrove, C. A., Moore, P. et al. A Randomized Trial Comparing Omicron-Containing Boosters with the Original Covid-19 Vaccine mRNA-1273. medRxiv. 2023;
[ModernaTX, Inc., 2020] ModernaTX, Inc.. A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19. clinicaltrials.gov. 2020; ModernaTX, Inc.. A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19. clinicaltrials.gov. 2020;
[Pajon R, 2022] Pajon R, Paila YD, Girard B et al. Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial. Nature medicine. 2022; Pajon R, Paila YD, Girard B et al. Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial. Nature medicine. 2022;
[Rojas C, 2022] Rojas C, Spector SA, Cale B et al. A framework and road map for rapid start-up and completion of a COVID-19 vaccine trial: A single clinical trial site experience. Journal of clinical and translational science. 2022;6(1):e21. Rojas C, Spector SA, Cale B et al. A framework and road map for rapid start-up and completion of a COVID-19 vaccine trial: A single clinical trial site experience. Journal of clinical and translational science. 2022;6(1):e21.
[Gilbert PB, 2021] Gilbert PB, Montefiori DC, McDermott AB et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science (New York, N.Y.). 2021;:eab3435. Gilbert PB, Montefiori DC, McDermott AB et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science (New York, N.Y.). 2021;:eab3435.
[El Sahly HM, 2021] El Sahly HM, Baden LR, Essink B et al. Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase. The New England journal of medicine. 2021;385(19):1774-1785. El Sahly HM, Baden LR, Essink B et al. Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase. The New England journal of medicine. 2021;385(19):1774-1785.
[Baden LR, 2021] Baden LR, El Sahly HM, Essink B et al. Phase 3 Trial of mRNA-1273 during the Delta-Variant Surge. The New England journal of medicine. 2021; Baden LR, El Sahly HM, Essink B et al. Phase 3 Trial of mRNA-1273 during the Delta-Variant Surge. The New England journal of medicine. 2021;
[Baden LR, 2021] Baden LR, El Sahly HM, Essink B et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. The New England journal of medicine. 2021;384(5):403-416. Baden LR, El Sahly HM, Essink B et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. The New England journal of medicine. 2021;384(5):403-416.
[El Sahly HM, 2022] El Sahly HM, Baden LR, Essink B et al. Humoral Immunogenicity of the mRNA-1273 Vaccine in the Phase 3 COVE Trial. The Journal of infectious diseases. 2022; El Sahly HM, Baden LR, Essink B et al. Humoral Immunogenicity of the mRNA-1273 Vaccine in the Phase 3 COVE Trial. The Journal of infectious diseases. 2022;
[Tan Tock Seng Hospital, 2021] Tan Tock Seng Hospital. Efficacy of Different COVID-19 Vaccine Combinations in Inducing Long-term Humoral Immunity [PRIBIVAC]. clinicaltrials.gov. 2021; Tan Tock Seng Hospital. Efficacy of Different COVID-19 Vaccine Combinations in Inducing Long-term Humoral Immunity [PRIBIVAC]. clinicaltrials.gov. 2021;
[Poh XY, 2022] Poh XY, Tan CW, Lee IR et al. Antibody response of heterologous vs homologous mRNA vaccine boosters against the SARS-CoV-2 Omicron variant: interim results from the PRIBIVAC study, A Randomized Clinical Trial. Clinical infectious diseases : an official pu Poh XY, Tan CW, Lee IR et al. Antibody response of heterologous vs homologous mRNA vaccine boosters against the SARS-CoV-2 Omicron variant: interim results from the PRIBIVAC study, A Randomized Clinical Trial. Clinical infectious diseases : an official pu
[Poh X, 2022] Poh X, Lee R, Lim C et al. Evaluation of the Safety and Immunogenicity of Different COVID-19 Vaccine Combinations in Healthy Individuals: Study Protocol for a Randomized, Subject-blinded, Controlled Phase 3 Trial [PRIBIVAC]. ResearchSquare. 2022; Poh X, Lee R, Lim C et al. Evaluation of the Safety and Immunogenicity of Different COVID-19 Vaccine Combinations in Healthy Individuals: Study Protocol for a Randomized, Subject-blinded, Controlled Phase 3 Trial [PRIBIVAC]. ResearchSquare. 2022;
[Poh XY, 2022] Poh XY, Lee IR, Lim C et al. Evaluation of the safety and immunogenicity of different COVID-19 vaccine combinations in healthy individuals: study protocol for a randomized, subject-blinded, controlled phase 3 trial [PRIBIVAC]. Trials. 2022;23(1):498. Poh XY, Lee IR, Lim C et al. Evaluation of the safety and immunogenicity of different COVID-19 vaccine combinations in healthy individuals: study protocol for a randomized, subject-blinded, controlled phase 3 trial [PRIBIVAC]. Trials. 2022;23(1):498.
[University Health Network, Toronto, 2021] University Health Network, Toronto. Third Dose of Moderna in Transplant Recipients. clinicaltrials.gov. 2021; University Health Network, Toronto. Third Dose of Moderna in Transplant Recipients. clinicaltrials.gov. 2021;
[Kumar D, 2021] Kumar D, Ferreira VH, Hall VG et al. Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine : Secondary Analysis of a Randomized Trial. Annals of internal medicine. 2021; Kumar D, Ferreira VH, Hall VG et al. Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine : Secondary Analysis of a Randomized Trial. Annals of internal medicine. 2021;
[Hall VG, 2021] Hall VG, Ferreira VH, Ku T et al. Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients. The New England journal of medicine. 2021; Hall VG, Ferreira VH, Ku T et al. Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients. The New England journal of medicine. 2021;
[University Medical Center Groningen, 2021] University Medical Center Groningen. RECOVAC Booster Vaccination Study. clinicaltrials.gov. 2021; University Medical Center Groningen. RECOVAC Booster Vaccination Study. clinicaltrials.gov. 2021;
[Kho MML, 2022] Kho MML, Messchendorp AL, Frölke SC et al. Alternative strategies to increase the immunogenicity of COVID-19 vaccines in kidney transplant recipients not responding to two or three doses of an mRNA vaccine (RECOVAC): a randomised clinical trial. The Lance Kho MML, Messchendorp AL, Frölke SC et al. Alternative strategies to increase the immunogenicity of COVID-19 vaccines in kidney transplant recipients not responding to two or three doses of an mRNA vaccine (RECOVAC): a randomised clinical trial. The Lance
[Erasmus Medical Center, 2021] Erasmus Medical Center. A Trial Among HealthCare Workers (HCW) Vaccinated With Janssen Vaccine: the SWITCH Trial. clinicaltrials.gov. 2021; Erasmus Medical Center. A Trial Among HealthCare Workers (HCW) Vaccinated With Janssen Vaccine: the SWITCH Trial. clinicaltrials.gov. 2021;
[Sablerolles RSG, 2022] Sablerolles RSG, Rietdijk WJR, Goorhuis A et al. Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming. The New England journal of medicine. 2022; Sablerolles RSG, Rietdijk WJR, Goorhuis A et al. Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming. The New England journal of medicine. 2022;
[Erasmus Medical Center, 2022] Erasmus Medical Center. SWITCH ON: Analysing the Immunogenicity of Additional Booster Vaccinations in HCW. clinicaltrials.gov. 2022; Erasmus Medical Center. SWITCH ON: Analysing the Immunogenicity of Additional Booster Vaccinations in HCW. clinicaltrials.gov. 2022;
[Ngoc Tan, 2022] Ngoc Tan, Daryl Geers, Roos Sablerolles et al. Evaluation of bivalent Omicron BA.1 booster vaccination after different priming regimens in healthcare workers (SWITCH ON): a randomized controlled trial. medRxiv. 2022; Ngoc Tan, Daryl Geers, Roos Sablerolles et al. Evaluation of bivalent Omicron BA.1 booster vaccination after different priming regimens in healthcare workers (SWITCH ON): a randomized controlled trial. medRxiv. 2022;
[Tan NH, 2022] Tan NH, Sablerolles RSG, Rietdijk WJR et al. Analyzing the immunogenicity of bivalent booster vaccinations in healthcare workers: The SWITCH ON trial protocol. Frontiers in immunology. 2022;13:1067749. Tan NH, Sablerolles RSG, Rietdijk WJR et al. Analyzing the immunogenicity of bivalent booster vaccinations in healthcare workers: The SWITCH ON trial protocol. Frontiers in immunology. 2022;13:1067749.
[Corbett KS, 2020] Corbett KS, Flynn B, Foulds KE et al. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. The New England journal of medicine. 2020;383(16):1544-1555. Corbett KS, Flynn B, Foulds KE et al. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. The New England journal of medicine. 2020;383(16):1544-1555.
[The GRADE Working Group, 2013] The GRADE Working Group. GRADE handbook for grading quality of evidence and strength of recommendations. Schünemann H, Bro?ek J, Guyatt G, Oxman A, editors. 2013; The GRADE Working Group. GRADE handbook for grading quality of evidence and strength of recommendations. Schünemann H, Bro?ek J, Guyatt G, Oxman A, editors. 2013;
[Sanofi Pasteur, a Sanofi Company, 2021] Sanofi Pasteur, a Sanofi Company. Study of a Quadrivalent High-Dose Influenza Vaccine and a Moderna COVID-19 Vaccine Administered Either Concomitantly or Singly in Participants 65 Years of Age and Older Previously Vaccinated With a 2-dose Schedule of Mode Sanofi Pasteur, a Sanofi Company. Study of a Quadrivalent High-Dose Influenza Vaccine and a Moderna COVID-19 Vaccine Administered Either Concomitantly or Singly in Participants 65 Years of Age and Older Previously Vaccinated With a 2-dose Schedule of Mode
[Mark Loeb, 2021] Mark Loeb. Third Dose of COVID-19 Vaccine in LTCF Residents. clinicaltrials.gov. 2021; Mark Loeb. Third Dose of COVID-19 Vaccine in LTCF Residents. clinicaltrials.gov. 2021;
[Rane MS, 2022] Rane MS, Robertson MM, Kulkarni SG et al. Effectiveness of Covid-19 vaccines against symptomatic and asymptomatic SARS-CoV-2 infections in an urgent care setting. Vaccine. 2022; Rane MS, Robertson MM, Kulkarni SG et al. Effectiveness of Covid-19 vaccines against symptomatic and asymptomatic SARS-CoV-2 infections in an urgent care setting. Vaccine. 2022;
[Levy M, 2021] Levy M, Recher M, Hubert H et al. Multisystem Inflammatory Syndrome in Children by COVID-19 Vaccination Status of Adolescents in France. JAMA. 2021; Levy M, Recher M, Hubert H et al. Multisystem Inflammatory Syndrome in Children by COVID-19 Vaccination Status of Adolescents in France. JAMA. 2021;
[González S, 2022] González S, Olszevicki S, Gaiano A et al. Effectiveness of BBIBP-CorV, BNT162b2 and mRNA-1273 vaccines against hospitalisations among children and adolescents during the Omicron outbreak in Argentina: A retrospective cohort study. Lancet Regional Health. González S, Olszevicki S, Gaiano A et al. Effectiveness of BBIBP-CorV, BNT162b2 and mRNA-1273 vaccines against hospitalisations among children and adolescents during the Omicron outbreak in Argentina: A retrospective cohort study. Lancet Regional Health.
[Castelli JM, 2022] Castelli JM, Rearte A, Olszevicki S et al. Effectiveness of mRNA-1273, BNT162b2, and BBIBP-CorV vaccines against infection and mortality in children in Argentina, during predominance of delta and omicron covid-19 variants: test negative, case-control stud Castelli JM, Rearte A, Olszevicki S et al. Effectiveness of mRNA-1273, BNT162b2, and BBIBP-CorV vaccines against infection and mortality in children in Argentina, during predominance of delta and omicron covid-19 variants: test negative, case-control stud
[Fleming-Dutra KE, 2023] Fleming-Dutra KE, Ciesla AA, Roper LE et al. Preliminary Estimates of Effectiveness of Monovalent mRNA Vaccines in Preventing Symptomatic SARS-CoV-2 Infection Among Children Aged 3-5 Years - Increasing Community Access to Testing Program, United States, J Fleming-Dutra KE, Ciesla AA, Roper LE et al. Preliminary Estimates of Effectiveness of Monovalent mRNA Vaccines in Preventing Symptomatic SARS-CoV-2 Infection Among Children Aged 3-5 Years - Increasing Community Access to Testing Program, United States, J
[Jorgensen SCJ, 2023] Jorgensen SCJ, Hernandez A, Fell DB et al. Maternal mRNA covid-19 vaccination during pregnancy and delta or omicron infection or hospital admission in infants: test negative design study. BMJ (Clinical research ed.). 2023;380:e074035. Jorgensen SCJ, Hernandez A, Fell DB et al. Maternal mRNA covid-19 vaccination during pregnancy and delta or omicron infection or hospital admission in infants: test negative design study. BMJ (Clinical research ed.). 2023;380:e074035.
[Golan Y et al., 2021] Golan Y, Prahl M, Cassidy AG, Gay C, Wu AHB, Jigmeddagva U, Lin CY, Gonzalez VJ, Basilio E, Warrier L, Buarpung S, Li L, Asiodu IV, Ahituv N, Flaherman VJ, Gaw SL. COVID-19 mRNA Vaccination in Lactation: Assessment of adverse effects and transfer of anti- Golan Y, Prahl M, Cassidy AG, Gay C, Wu AHB, Jigmeddagva U, Lin CY, Gonzalez VJ, Basilio E, Warrier L, Buarpung S, Li L, Asiodu IV, Ahituv N, Flaherman VJ, Gaw SL. COVID-19 mRNA Vaccination in Lactation: Assessment of adverse effects and transfer of anti-
[]
[FDA, 2020] FDA. FDA Briefing Document: Moderna COVID-19 Vaccine. Vaccines and Related Biological Products Advisory Committee Meeting December 17, 2020. 2020; FDA. FDA Briefing Document: Moderna COVID-19 Vaccine. Vaccines and Related Biological Products Advisory Committee Meeting December 17, 2020. 2020;
[Speich B, 2022] Speich B, Chammartin F, Abela IA et al. Antibody response in immunocompromised patients after the administration of SARS-CoV-2 vaccine BNT162b2 or mRNA-1273: A randomised controlled trial. Clinical infectious diseases : an official publication of the Infe Speich B, Chammartin F, Abela IA et al. Antibody response in immunocompromised patients after the administration of SARS-CoV-2 vaccine BNT162b2 or mRNA-1273: A randomised controlled trial. Clinical infectious diseases : an official publication of the Infe
[Irene Schiavetti, 2022] Irene Schiavetti, Cinzia Cordioli, Maria Laura Stromillo et al. Breakthrough SARS-CoV-2 infections in MS patients on disease modifying therapies. medRxiv. 2022; Irene Schiavetti, Cinzia Cordioli, Maria Laura Stromillo et al. Breakthrough SARS-CoV-2 infections in MS patients on disease modifying therapies. medRxiv. 2022;
[Huang HJ, 2022] Huang HJ, Yi SG, Mobley CM et al. Early humoral immune response to two doses of severe acute respiratory syndrome coronavirus 2 vaccine in a diverse group of solid organ transplant candidates and recipients. Clinical transplantation. 2022;:e14600. Huang HJ, Yi SG, Mobley CM et al. Early humoral immune response to two doses of severe acute respiratory syndrome coronavirus 2 vaccine in a diverse group of solid organ transplant candidates and recipients. Clinical transplantation. 2022;:e14600.
[Tenforde MW, 2022] Tenforde MW, Patel MM, Gaglani M et al. Effectiveness of a Third Dose of Pfizer-BioNTech and Moderna Vaccines in Preventing COVID-19 Hospitalization Among Immunocompetent and Immunocompromised Adults - United States, August-December 2021. MMWR. Morbidity Tenforde MW, Patel MM, Gaglani M et al. Effectiveness of a Third Dose of Pfizer-BioNTech and Moderna Vaccines in Preventing COVID-19 Hospitalization Among Immunocompetent and Immunocompromised Adults - United States, August-December 2021. MMWR. Morbidity
[Li LL, 2022] Li LL, Zheng C, La J et al. Impact of prior SARS-CoV-2 infection on incidence of hospitalization and adverse events following mRNA SARS-CoV-2 vaccination: A nationwide, retrospective cohort study. Vaccine. 2022; Li LL, Zheng C, La J et al. Impact of prior SARS-CoV-2 infection on incidence of hospitalization and adverse events following mRNA SARS-CoV-2 vaccination: A nationwide, retrospective cohort study. Vaccine. 2022;
[Aharon D, 2022] Aharon D, Lederman M, Ghofranian A et al. In Vitro Fertilization and Early Pregnancy Outcomes After Coronavirus Disease 2019 (COVID-19) Vaccination. Obstetrics and gynecology. 2022; Aharon D, Lederman M, Ghofranian A et al. In Vitro Fertilization and Early Pregnancy Outcomes After Coronavirus Disease 2019 (COVID-19) Vaccination. Obstetrics and gynecology. 2022;
[Lombardi A, 2021] Lombardi A, Butta GM, Donnici L et al. Anti-spike antibodies and neutralising antibody activity in people living with HIV vaccinated with COVID-19 mRNA-1273 vaccine: a prospective single-centre cohort study. The Lancet regional health. Europe. 2021;:10028 Lombardi A, Butta GM, Donnici L et al. Anti-spike antibodies and neutralising antibody activity in people living with HIV vaccinated with COVID-19 mRNA-1273 vaccine: a prospective single-centre cohort study. The Lancet regional health. Europe. 2021;:10028
[Sheng WH, 2022] Sheng WH, Chang SY, Lin PH et al. Immune response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 vaccination compared with homologous ChAdOx1-nCoV-19 or homologous mRNA-1273 vaccination. Journal of the Formosan Medical Association = Taiwan yi zhi. 2 Sheng WH, Chang SY, Lin PH et al. Immune response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 vaccination compared with homologous ChAdOx1-nCoV-19 or homologous mRNA-1273 vaccination. Journal of the Formosan Medical Association = Taiwan yi zhi. 2
[Lin KY, 2022] Lin KY, Hsieh MJ, Chang SY et al. Serological response after COVID-19 mRNA-1273 booster dose in immunocompromised patients, Taiwan, July to August 2021. Journal of the Formosan Medical Association = Taiwan yi zhi. 2022; Lin KY, Hsieh MJ, Chang SY et al. Serological response after COVID-19 mRNA-1273 booster dose in immunocompromised patients, Taiwan, July to August 2021. Journal of the Formosan Medical Association = Taiwan yi zhi. 2022;
[Coburn SB, 2022] Coburn SB, Humes E, Lang R et al. Analysis of Postvaccination Breakthrough COVID-19 Infections Among Adults With HIV in the United States. JAMA network open. 2022;5(6):e2215934. Coburn SB, Humes E, Lang R et al. Analysis of Postvaccination Breakthrough COVID-19 Infections Among Adults With HIV in the United States. JAMA network open. 2022;5(6):e2215934.
[Risk M, 2022] Risk M, Hayek SS, Schiopu E et al. COVID-19 vaccine effectiveness against omicron (B.1.1.529) variant infection and hospitalisation in patients taking immunosuppressive medications: a retrospective cohort study. The Lancet. Rheumatology. 2022; Risk M, Hayek SS, Schiopu E et al. COVID-19 vaccine effectiveness against omicron (B.1.1.529) variant infection and hospitalisation in patients taking immunosuppressive medications: a retrospective cohort study. The Lancet. Rheumatology. 2022;
[Peter J. Embi, 2022] Peter J. Embi, Matthew E. Levy, Palak Patel et al. Effectiveness of COVID-19 Vaccines at Preventing Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompromised Adults: An Observational Study of Real-World Data Across 10 US Peter J. Embi, Matthew E. Levy, Palak Patel et al. Effectiveness of COVID-19 Vaccines at Preventing Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompromised Adults: An Observational Study of Real-World Data Across 10 US
[Furer V, 2022] Furer V, Eviatar T, Freund T et al. Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study. Annals of the rheuma Furer V, Eviatar T, Freund T et al. Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study. Annals of the rheuma
[Smith JB, 2022] Smith JB, Gonzales EG, Li BH et al. Analysis of Rituximab Use, Time Between Rituximab and SARS-CoV-2 Vaccination, and COVID-19 Hospitalization or Death in Patients With Multiple Sclerosis. JAMA network open. 2022;5(12):e2248664. Smith JB, Gonzales EG, Li BH et al. Analysis of Rituximab Use, Time Between Rituximab and SARS-CoV-2 Vaccination, and COVID-19 Hospitalization or Death in Patients With Multiple Sclerosis. JAMA network open. 2022;5(12):e2248664.
[Saman Saadat, 2021] Saman Saadat, Zahra Rikhtegaran-Tehrani, James Logue et al. Single Dose Vaccination in Healthcare Workers Previously Infected with SARS-CoV-2. medRxiv. 2021; Saman Saadat, Zahra Rikhtegaran-Tehrani, James Logue et al. Single Dose Vaccination in Healthcare Workers Previously Infected with SARS-CoV-2. medRxiv. 2021;
[Chung H, 2021] Chung H, He S, Nasreen S et al. Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study. BMJ (Clinical research ed.). 2021;374:n1943. Chung H, He S, Nasreen S et al. Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study. BMJ (Clinical research ed.). 2021;374:n1943.
[Flacco ME, 2021] Flacco ME, Soldato G, Acuti Martellucci C et al. Interim Estimates of COVID-19 Vaccine Effectiveness in a Mass Vaccination Setting: Data from an Italian Province. Vaccines. 2021;9(6). Flacco ME, Soldato G, Acuti Martellucci C et al. Interim Estimates of COVID-19 Vaccine Effectiveness in a Mass Vaccination Setting: Data from an Italian Province. Vaccines. 2021;9(6).
[Pawlowski C, 2021] Pawlowski C, Lenehan P, Puranik A et al. FDA-authorized mRNA COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system. Med (New York, N.Y.). 2021; Pawlowski C, Lenehan P, Puranik A et al. FDA-authorized mRNA COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system. Med (New York, N.Y.). 2021;
[Amanda Zheutlin, 2022] Amanda Zheutlin, Miles Ott, Ran Sun et al. Durability of Protection against COVID-19 Breakthrough Infections and Severe Disease by Vaccines in the United States. medRxiv. 2022; Amanda Zheutlin, Miles Ott, Ran Sun et al. Durability of Protection against COVID-19 Breakthrough Infections and Severe Disease by Vaccines in the United States. medRxiv. 2022;
[Sevda Molani, 2022] Sevda Molani, Andrew M Baumgartner, Yeon Mi Hwang et al. Time to reinfection and vaccine breakthrough SARS-CoV-2 infections: a retrospective cohort study. medRxiv. 2022; Sevda Molani, Andrew M Baumgartner, Yeon Mi Hwang et al. Time to reinfection and vaccine breakthrough SARS-CoV-2 infections: a retrospective cohort study. medRxiv. 2022;
[Chadeau-Hyam M, 2022] Chadeau-Hyam M, Wang H, Eales O et al. SARS-CoV-2 infection and vaccine effectiveness in England (REACT-1): a series of cross-sectional random community surveys. The Lancet. Respiratory medicine. 2022; Chadeau-Hyam M, Wang H, Eales O et al. SARS-CoV-2 infection and vaccine effectiveness in England (REACT-1): a series of cross-sectional random community surveys. The Lancet. Respiratory medicine. 2022;
[Drawz PE, 2022] Drawz PE, DeSilva M, Bodurtha P et al. Effectiveness of BNT162b2 and mRNA-1273 Second Doses and Boosters for SARS-CoV-2 infection and SARS-CoV-2 Related Hospitalizations: A Statewide Report from the Minnesota Electronic Health Record Consortium. Clinical Drawz PE, DeSilva M, Bodurtha P et al. Effectiveness of BNT162b2 and mRNA-1273 Second Doses and Boosters for SARS-CoV-2 infection and SARS-CoV-2 Related Hospitalizations: A Statewide Report from the Minnesota Electronic Health Record Consortium. Clinical
[Emily Roberts, 2022] Emily Roberts, Tian Gu, Bhramar Mukherjee et al. Estimating COVID-19 Vaccination Effectiveness Using Electronic Health Records of an Academic Medical Center in Michigan. medRxiv. 2022; Emily Roberts, Tian Gu, Bhramar Mukherjee et al. Estimating COVID-19 Vaccination Effectiveness Using Electronic Health Records of an Academic Medical Center in Michigan. medRxiv. 2022;
[Winkelman TNA, 2022] Winkelman TNA, Rai NK, Bodurtha PJ et al. Trends in COVID-19 Vaccine Administration and Effectiveness Through October 2021. JAMA network open. 2022;5(3):e225018. Winkelman TNA, Rai NK, Bodurtha PJ et al. Trends in COVID-19 Vaccine Administration and Effectiveness Through October 2021. JAMA network open. 2022;5(3):e225018.
[Oren Miron, 2021] Oren Miron, Rachel Wilf-Miron, Nadav Davidovitch. Effectiveness of COVID-19 Vaccines BNT162b2 and mRNA-1273 by Days from Vaccination: A Reanalysis of Clinical Trial Data. SSRN. 2021; Oren Miron, Rachel Wilf-Miron, Nadav Davidovitch. Effectiveness of COVID-19 Vaccines BNT162b2 and mRNA-1273 by Days from Vaccination: A Reanalysis of Clinical Trial Data. SSRN. 2021;
[Lin DY, 2022] Lin DY, Gu Y, Xu Y et al. Association of Primary and Booster Vaccination and Prior Infection With SARS-CoV-2 Infection and Severe COVID-19 Outcomes. JAMA. 2022; Lin DY, Gu Y, Xu Y et al. Association of Primary and Booster Vaccination and Prior Infection With SARS-CoV-2 Infection and Severe COVID-19 Outcomes. JAMA. 2022;
[Chung H, 2022] Chung H, Austin PC, Brown KA et al. Effectiveness of COVID-19 Vaccines Over Time Prior to Omicron Emergence in Ontario, Canada: Test-Negative Design Study. Open forum infectious diseases. 2022;9(9):ofac449. Chung H, Austin PC, Brown KA et al. Effectiveness of COVID-19 Vaccines Over Time Prior to Omicron Emergence in Ontario, Canada: Test-Negative Design Study. Open forum infectious diseases. 2022;9(9):ofac449.
[Weng CH, 2023] Weng CH, Zhou S, Saal A et al. BNT162b2 and mRNA-1273 Vaccine Effectiveness against SARS-CoV-2 and Variants in the Urban Underserved Population. Rhode Island medical journal (2013). 2023;106(1):26-28. Weng CH, Zhou S, Saal A et al. BNT162b2 and mRNA-1273 Vaccine Effectiveness against SARS-CoV-2 and Variants in the Urban Underserved Population. Rhode Island medical journal (2013). 2023;106(1):26-28.
[Puranik A, 2022] Puranik A, Lenehan PJ, O'Horo JC et al. Durability analysis of the highly effective mRNA-1273 vaccine against COVID-19. PNAS nexus. 2022;1(2):pgac058. Puranik A, Lenehan PJ, O'Horo JC et al. Durability analysis of the highly effective mRNA-1273 vaccine against COVID-19. PNAS nexus. 2022;1(2):pgac058.
[Bello-Chavolla OY, 2023] Bello-Chavolla OY, Antonio-Villa NE, Valdés-Ferrer SI et al. Effectiveness of a nation-wide COVID-19 vaccination program in Mexico against symptomatic COVID-19, hospitalizations, and death: a retrospective analysis of national surveillance data. Internati Bello-Chavolla OY, Antonio-Villa NE, Valdés-Ferrer SI et al. Effectiveness of a nation-wide COVID-19 vaccination program in Mexico against symptomatic COVID-19, hospitalizations, and death: a retrospective analysis of national surveillance data. Internati
[Kayoko Shioda, 2023] Kayoko Shioda, Alexander Breskin, Pravara Harati et al. Comparative Effectiveness of Alternative Intervals between First and Second Doses of the mRNA COVID-19 Vaccines: a Trial Emulation Approach. medRxiv. 2023; Kayoko Shioda, Alexander Breskin, Pravara Harati et al. Comparative Effectiveness of Alternative Intervals between First and Second Doses of the mRNA COVID-19 Vaccines: a Trial Emulation Approach. medRxiv. 2023;
[Theodore Lytras, 2022] Theodore Lytras, Flora Kontopidou, Angeliki Lambrou et al. Comparative effectiveness of COVID-19 vaccination against death and severe disease in an ongoing nationwide mass vaccination campaign. medRxiv. 2022; Theodore Lytras, Flora Kontopidou, Angeliki Lambrou et al. Comparative effectiveness of COVID-19 vaccination against death and severe disease in an ongoing nationwide mass vaccination campaign. medRxiv. 2022;
[Yuanyuan Fu, 2022] Yuanyuan Fu, Kaipeng Wu, Zhanwei Wang et al. Effectiveness of COVID-19 Vaccines in the US: Real-World Evidence from the National COVID Cohort Collaborative. SSRN. 2022; Yuanyuan Fu, Kaipeng Wu, Zhanwei Wang et al. Effectiveness of COVID-19 Vaccines in the US: Real-World Evidence from the National COVID Cohort Collaborative. SSRN. 2022;
[Anzalone AJ, 2023] Anzalone AJ, Sun J, Vinson AJ et al. Community risks for SARS-CoV-2 infection among fully vaccinated US adults by rurality: A retrospective cohort study from the National COVID Cohort Collaborative. PloS one. 2023;18(1):e0279968. Anzalone AJ, Sun J, Vinson AJ et al. Community risks for SARS-CoV-2 infection among fully vaccinated US adults by rurality: A retrospective cohort study from the National COVID Cohort Collaborative. PloS one. 2023;18(1):e0279968.
[Bouillon K, 2022] Bouillon K, Baricault B, Botton J et al. Effectiveness of BNT162b2, mRNA-1273, and ChAdOx1-S vaccines against severe covid-19 outcomes in a nationwide mass vaccination setting: cohort study. BMJ medicine. 2022;1(1):e000104. Bouillon K, Baricault B, Botton J et al. Effectiveness of BNT162b2, mRNA-1273, and ChAdOx1-S vaccines against severe covid-19 outcomes in a nationwide mass vaccination setting: cohort study. BMJ medicine. 2022;1(1):e000104.
[de Arriba Fernández A, 2023] de Arriba Fernández A, Bilbao JLA, Francés AE et al. Evaluation of persistent COVID and SARS-CoV-2 reinfection in a cohort of patients on the island of Gran Canaria, Spain. Semergen. 2023;49(5):101939. de Arriba Fernández A, Bilbao JLA, Francés AE et al. Evaluation of persistent COVID and SARS-CoV-2 reinfection in a cohort of patients on the island of Gran Canaria, Spain. Semergen. 2023;49(5):101939.
[Abu-Raddad LJ, 2022] Abu-Raddad LJ, Chemaitelly H, Bertollini R et al. Effectiveness of mRNA-1273 and BNT162b2 Vaccines in Qatar. The New England journal of medicine. 2022; Abu-Raddad LJ, Chemaitelly H, Bertollini R et al. Effectiveness of mRNA-1273 and BNT162b2 Vaccines in Qatar. The New England journal of medicine. 2022;
[Lafon E, 2022] Lafon E, Jäger M, Bauer A et al. Comparative analyses of IgG/IgA neutralizing effects induced by three COVID-19 vaccines against variants of concern. The Journal of allergy and clinical immunology. 2022; Lafon E, Jäger M, Bauer A et al. Comparative analyses of IgG/IgA neutralizing effects induced by three COVID-19 vaccines against variants of concern. The Journal of allergy and clinical immunology. 2022;
[Janssen C, 2022] Janssen C, Cachanado M, Ninove L et al. Immunogenicity and reactogenicity of heterologous and homologous mRNA-1273 and BNT162b2 vaccination: A multicenter non-inferiority randomized trial. EClinicalMedicine. 2022;48:101444. Janssen C, Cachanado M, Ninove L et al. Immunogenicity and reactogenicity of heterologous and homologous mRNA-1273 and BNT162b2 vaccination: A multicenter non-inferiority randomized trial. EClinicalMedicine. 2022;48:101444.
[Kanokudom S, 2022] Kanokudom S, Assawakosri S, Suntronwong N et al. Comparison of the reactogenicity and immunogenicity of a reduced and standard booster dose of the mRNA COVID-19 vaccine in healthy adults after two doses of inactivated vaccine. Vaccine. 2022; Kanokudom S, Assawakosri S, Suntronwong N et al. Comparison of the reactogenicity and immunogenicity of a reduced and standard booster dose of the mRNA COVID-19 vaccine in healthy adults after two doses of inactivated vaccine. Vaccine. 2022;
[Suntronwong N, 2022] Suntronwong N, Kanokudom S, Auphimai C et al. Effects of boosted mRNA and adenoviral-vectored vaccines on immune responses to omicron BA.1 and BA.2 following the heterologous CoronaVac/AZD1222 vaccination. Journal of medical virology. 2022; Suntronwong N, Kanokudom S, Auphimai C et al. Effects of boosted mRNA and adenoviral-vectored vaccines on immune responses to omicron BA.1 and BA.2 following the heterologous CoronaVac/AZD1222 vaccination. Journal of medical virology. 2022;
[Prasert Assantachai, 2022] Prasert Assantachai, Suvimol Niyomnaitham, Wichai Chatthanawaree et al. Immunogenicity and reactogenicity of mRNA COVID-19 vaccine booster administered by intradermal or intramuscular route in Thai older adults. medRxiv. 2022; Prasert Assantachai, Suvimol Niyomnaitham, Wichai Chatthanawaree et al. Immunogenicity and reactogenicity of mRNA COVID-19 vaccine booster administered by intradermal or intramuscular route in Thai older adults. medRxiv. 2022;
[Nasreen, S., 2021] Nasreen, S., Chung, H., He, S. et al. Effectiveness of mRNA and ChAdOx1 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe outcomes with variants of concern in Ontario. medRxiv. 2021; Nasreen, S., Chung, H., He, S. et al. Effectiveness of mRNA and ChAdOx1 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe outcomes with variants of concern in Ontario. medRxiv. 2021;
[Fabiani M, 2022] Fabiani M, Puopolo M, Morciano C et al. Effectiveness of mRNA vaccines and waning of protection against SARS-CoV-2 infection and severe covid-19 during predominant circulation of the delta variant in Italy: retrospective cohort study. BMJ (Clinical resear Fabiani M, Puopolo M, Morciano C et al. Effectiveness of mRNA vaccines and waning of protection against SARS-CoV-2 infection and severe covid-19 during predominant circulation of the delta variant in Italy: retrospective cohort study. BMJ (Clinical resear
[Accorsi EK, 2022] Accorsi EK, Britton A, Fleming-Dutra KE et al. Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants. JAMA. 2022; Accorsi EK, Britton A, Fleming-Dutra KE et al. Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants. JAMA. 2022;
[Buchan SA, 2022] Buchan SA, Chung H, Brown KA et al. Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes. JAMA network open. 2022;5(9):e2232760. Buchan SA, Chung H, Brown KA et al. Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes. JAMA network open. 2022;5(9):e2232760.
[Johnson AG, 2022] Johnson AG, Amin AB, Ali AR et al. COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence - 25 U.S. Jurisdictions, April 4-December 25, 2021. M Johnson AG, Amin AB, Ali AR et al. COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence - 25 U.S. Jurisdictions, April 4-December 25, 2021. M
[Thompson MG, 2022] Thompson MG, Natarajan K, Irving SA et al. Effectiveness of a Third Dose of mRNA Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominanc Thompson MG, Natarajan K, Irving SA et al. Effectiveness of a Third Dose of mRNA Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominanc
[Irina Kislaya, 2022] Irina Kislaya, ANDRE PERALTA SANTOS, Vitor Borges et al. Comparative complete scheme and booster effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infections with SARS-CoV-2 Omicron (BA.1) and Delta (B.1.617.2) variants. medRxiv. 2022; Irina Kislaya, ANDRE PERALTA SANTOS, Vitor Borges et al. Comparative complete scheme and booster effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infections with SARS-CoV-2 Omicron (BA.1) and Delta (B.1.617.2) variants. medRxiv. 2022;
[Andrews N, 2022] Andrews N, Stowe J, Kirsebom F et al. Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. The New England journal of medicine. 2022; Andrews N, Stowe J, Kirsebom F et al. Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. The New England journal of medicine. 2022;
[Young-Xu Y, 2022] Young-Xu Y, Zwain GM, Izurieta HS et al. Effectiveness of mRNA COVID-19 vaccines against Omicron and Delta variants in a matched test-negative case-control study among US veterans. BMJ open. 2022;12(8):e063935. Young-Xu Y, Zwain GM, Izurieta HS et al. Effectiveness of mRNA COVID-19 vaccines against Omicron and Delta variants in a matched test-negative case-control study among US veterans. BMJ open. 2022;12(8):e063935.
[Ferdinands JM, 2022] Ferdinands JM, Rao S, Dixon BE et al. Waning of vaccine effectiveness against moderate and severe covid-19 among adults in the US from the VISION network: test negative, case-control study. BMJ (Clinical research ed.). 2022;379:e072141. Ferdinands JM, Rao S, Dixon BE et al. Waning of vaccine effectiveness against moderate and severe covid-19 among adults in the US from the VISION network: test negative, case-control study. BMJ (Clinical research ed.). 2022;379:e072141.
[Rennert L, 2022] Rennert L, Ma Z, McMahan CS et al. Effectiveness and protection duration of Covid-19 vaccines and previous infection against any SARS-CoV-2 infection in young adults. Nature communications. 2022;13(1):3946. Rennert L, Ma Z, McMahan CS et al. Effectiveness and protection duration of Covid-19 vaccines and previous infection against any SARS-CoV-2 infection in young adults. Nature communications. 2022;13(1):3946.
[Anne J. Huiberts, 2023] Anne J. Huiberts, Brechje de Gier, Christina E Hoeve et al. Vaccine effectiveness of primary and booster COVID-19 vaccinations against SARS-CoV-2 infection in the Netherlands from 12 July 2021 to 6 June 2022: a prospective cohort study. medRxiv. 2023; Anne J. Huiberts, Brechje de Gier, Christina E Hoeve et al. Vaccine effectiveness of primary and booster COVID-19 vaccinations against SARS-CoV-2 infection in the Netherlands from 12 July 2021 to 6 June 2022: a prospective cohort study. medRxiv. 2023;
[Hiam Chemaitelly, 2022] Hiam Chemaitelly, Houssein H. Ayoub, Sawsan AlMukdad et al. Duration of protection of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 Omicron infection in Qatar. medRxiv. 2022; Hiam Chemaitelly, Houssein H. Ayoub, Sawsan AlMukdad et al. Duration of protection of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 Omicron infection in Qatar. medRxiv. 2022;
[Nabin K Shrestha, 2022] Nabin K Shrestha, Priyanka Shrestha, Patrick C Burke et al. Coronavirus Disease 2019 (COVID-19) Vaccine Boosting in Persons Already Protected by Natural or Vaccine-Induced Immunity. medRxiv. 2022; Nabin K Shrestha, Priyanka Shrestha, Patrick C Burke et al. Coronavirus Disease 2019 (COVID-19) Vaccine Boosting in Persons Already Protected by Natural or Vaccine-Induced Immunity. medRxiv. 2022;
[Abu-Raddad LJ, 2022] Abu-Raddad LJ, Chemaitelly H, Ayoub HH et al. Effect of mRNA Vaccine Boosters against SARS-CoV-2 Omicron Infection in Qatar. The New England journal of medicine. 2022; Abu-Raddad LJ, Chemaitelly H, Ayoub HH et al. Effect of mRNA Vaccine Boosters against SARS-CoV-2 Omicron Infection in Qatar. The New England journal of medicine. 2022;
[Ng OT, 2022] Ng OT, Marimuthu K, Lim N et al. Analysis of COVID-19 Incidence and Severity Among Adults Vaccinated With 2-Dose mRNA COVID-19 or Inactivated SARS-CoV-2 Vaccines With and Without Boosters in Singapore. JAMA network open. 2022;5(8):e2228900. Ng OT, Marimuthu K, Lim N et al. Analysis of COVID-19 Incidence and Severity Among Adults Vaccinated With 2-Dose mRNA COVID-19 or Inactivated SARS-CoV-2 Vaccines With and Without Boosters in Singapore. JAMA network open. 2022;5(8):e2228900.
[Monge S, 2022] Monge S, Rojas-Benedicto A, Olmedo C et al. Effectiveness of mRNA vaccine boosters against infection with the SARS-CoV-2 omicron (B.1.1.529) variant in Spain: a nationwide cohort study. The Lancet. Infectious diseases. 2022; Monge S, Rojas-Benedicto A, Olmedo C et al. Effectiveness of mRNA vaccine boosters against infection with the SARS-CoV-2 omicron (B.1.1.529) variant in Spain: a nationwide cohort study. The Lancet. Infectious diseases. 2022;
[Ioannou GN, 2022] Ioannou GN, Bohnert ASB, O'Hare AM et al. Effectiveness of mRNA COVID-19 Vaccine Boosters Against Infection, Hospitalization, and Death: A Target Trial Emulation in the Omicron (B.1.1.529) Variant Era. Annals of internal medicine. 2022; Ioannou GN, Bohnert ASB, O'Hare AM et al. Effectiveness of mRNA COVID-19 Vaccine Boosters Against Infection, Hospitalization, and Death: A Target Trial Emulation in the Omicron (B.1.1.529) Variant Era. Annals of internal medicine. 2022;
[Grewal R, 2022] Grewal R, Kitchen SA, Nguyen L et al. Effectiveness of a fourth dose of covid-19 mRNA vaccine against the omicron variant among long term care residents in Ontario, Canada: test negative design study. BMJ (Clinical research ed.). 2022;378:e071502. Grewal R, Kitchen SA, Nguyen L et al. Effectiveness of a fourth dose of covid-19 mRNA vaccine against the omicron variant among long term care residents in Ontario, Canada: test negative design study. BMJ (Clinical research ed.). 2022;378:e071502.
[Agrawal U, 2022] Agrawal U, Bedston S, McCowan C et al. Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and W Agrawal U, Bedston S, McCowan C et al. Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and W
[Hung Fu Tseng, 2022] Hung Fu Tseng, Bradley K. Ackerson, Katia J. Bruxvoort et al. Effectiveness of mRNA-1273 against infection and COVID-19 hospitalization with SARS-CoV-2 Omicron subvariants: BA.1, BA.2, BA.2.12.1, BA.4, and BA.5. medRxiv. 2022; Hung Fu Tseng, Bradley K. Ackerson, Katia J. Bruxvoort et al. Effectiveness of mRNA-1273 against infection and COVID-19 hospitalization with SARS-CoV-2 Omicron subvariants: BA.1, BA.2, BA.2.12.1, BA.4, and BA.5. medRxiv. 2022;
[Baum U, 2022] Baum U, Poukka E, Leino T et al. High vaccine effectiveness against severe COVID-19 in the elderly in Finland before and after the emergence of Omicron. BMC infectious diseases. 2022;22(1):816. Baum U, Poukka E, Leino T et al. High vaccine effectiveness against severe COVID-19 in the elderly in Finland before and after the emergence of Omicron. BMC infectious diseases. 2022;22(1):816.
[Intawong K, 2022] Intawong K, Chariyalertsak S, Chalom K et al. Effectiveness of heterologous third and fourth dose COVID-19 vaccine schedules for SARS-CoV-2 infection during delta and omicron predominance in Thailand: A test-negative, case-control study. The Lancet region Intawong K, Chariyalertsak S, Chalom K et al. Effectiveness of heterologous third and fourth dose COVID-19 vaccine schedules for SARS-CoV-2 infection during delta and omicron predominance in Thailand: A test-negative, case-control study. The Lancet region
[Grewal R, 2022] Grewal R, Nguyen L, Buchan SA et al. Effectiveness and Duration of Protection of a Fourth Dose of COVID-19 mRNA Vaccine among Long-Term Care Residents in Ontario, Canada. The Journal of infectious diseases. 2022; Grewal R, Nguyen L, Buchan SA et al. Effectiveness and Duration of Protection of a Fourth Dose of COVID-19 mRNA Vaccine among Long-Term Care Residents in Ontario, Canada. The Journal of infectious diseases. 2022;
[Tseng HF, 2023] Tseng HF, Ackerson BK, Bruxvoort KJ et al. Effectiveness of mRNA-1273 vaccination against SARS-CoV-2 omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5. Nature communications. 2023;14(1):189. Tseng HF, Ackerson BK, Bruxvoort KJ et al. Effectiveness of mRNA-1273 vaccination against SARS-CoV-2 omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5. Nature communications. 2023;14(1):189.
[Cerqueira-Silva T, 2023] Cerqueira-Silva T, Shah SA, Robertson C et al. Effectiveness of mRNA boosters after homologous primary series with BNT162b2 or ChAdOx1 against symptomatic infection and severe COVID-19 in Brazil and Scotland: A test-negative design case-control study. PLo Cerqueira-Silva T, Shah SA, Robertson C et al. Effectiveness of mRNA boosters after homologous primary series with BNT162b2 or ChAdOx1 against symptomatic infection and severe COVID-19 in Brazil and Scotland: A test-negative design case-control study. PLo
[Vella G, 2023] Vella G, Genovese D, Belluzzo M et al. Effectiveness of mRNA Vaccine Booster against SARS-CoV-2 Infection and COVID-19 in the Adult Population during the First Three Months of the Omicron Wave in Sicily. Healthcare (Basel, Switzerland). 2023;11(3). Vella G, Genovese D, Belluzzo M et al. Effectiveness of mRNA Vaccine Booster against SARS-CoV-2 Infection and COVID-19 in the Adult Population during the First Three Months of the Omicron Wave in Sicily. Healthcare (Basel, Switzerland). 2023;11(3).
[Tenforde MW, 2023] Tenforde MW, Weber ZA, Natarajan K et al. Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults - VISION Network, Nine Stat Tenforde MW, Weber ZA, Natarajan K et al. Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults - VISION Network, Nine Stat
[Maeda H, 2023] Maeda H, Saito N, Igarashi A et al. Effectiveness of mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections during the SARS-CoV-2 Omicron BA.1 and BA.2 epidemic in Japan: Vaccine Effectiveness Real-time Surveillance for SARS-CoV-2 (VERSUS). Expe Maeda H, Saito N, Igarashi A et al. Effectiveness of mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections during the SARS-CoV-2 Omicron BA.1 and BA.2 epidemic in Japan: Vaccine Effectiveness Real-time Surveillance for SARS-CoV-2 (VERSUS). Expe
[Benotmane I, 2021] Benotmane I, Gautier G, Perrin P et al. Antibody Response After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients With Minimal Serologic Response to 2 Doses. JAMA. 2021; Benotmane I, Gautier G, Perrin P et al. Antibody Response After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients With Minimal Serologic Response to 2 Doses. JAMA. 2021;
[Haggenburg S, 2022] Haggenburg S, Hofsink Q, Lissenberg-Witte BI et al. Antibody Response in Immunocompromised Patients With Hematologic Cancers Who Received a 3-Dose mRNA-1273 Vaccination Schedule for COVID-19. JAMA oncology. 2022; Haggenburg S, Hofsink Q, Lissenberg-Witte BI et al. Antibody Response in Immunocompromised Patients With Hematologic Cancers Who Received a 3-Dose mRNA-1273 Vaccination Schedule for COVID-19. JAMA oncology. 2022;
[Laith J Abu-Raddad, 2022] Laith J Abu-Raddad, Hiam Chemaitelly, Houssein H. Ayoub et al. Effectiveness of BNT162b2 and mRNA-1273 COVID-19 boosters against SARS-CoV-2 Omicron (B.1.1.529) infection in Qatar. medRxiv. 2022; Laith J Abu-Raddad, Hiam Chemaitelly, Houssein H. Ayoub et al. Effectiveness of BNT162b2 and mRNA-1273 COVID-19 boosters against SARS-CoV-2 Omicron (B.1.1.529) infection in Qatar. medRxiv. 2022;
[Kevin W McConeghy, 2022] Kevin W McConeghy, Barbara Bardenheier, Andrew W Huang et al. Effectiveness of a SARS-CoV-2 mRNA vaccine booster dose for prevention of infection, hospitalization or death in two nation-wide nursing home systems. medRxiv. 2022; Kevin W McConeghy, Barbara Bardenheier, Andrew W Huang et al. Effectiveness of a SARS-CoV-2 mRNA vaccine booster dose for prevention of infection, hospitalization or death in two nation-wide nursing home systems. medRxiv. 2022;
[Buchan, S. A., 2022] Buchan, S. A., Chung, H., Brown, K. A. et al. Effectiveness of COVID-19 vaccines against Omicron or Delta symptomatic infection and severe outcomes. medRxiv. 2022; Buchan, S. A., Chung, H., Brown, K. A. et al. Effectiveness of COVID-19 vaccines against Omicron or Delta symptomatic infection and severe outcomes. medRxiv. 2022;
[Tan SHX, 2022] Tan SHX, Pung R, Wang LF et al. Association of Homologous and Heterologous Vaccine Boosters With COVID-19 Incidence and Severity in Singapore. JAMA. 2022; Tan SHX, Pung R, Wang LF et al. Association of Homologous and Heterologous Vaccine Boosters With COVID-19 Incidence and Severity in Singapore. JAMA. 2022;
[Mehta HB, 2022] Mehta HB, Li S, Goodwin JS. Effectiveness of COVID-19 Booster on the Risk of Hospitalization Among Medicare Beneficiaries. Mayo Clinic proceedings. 2022;97(10):1780-1793. Mehta HB, Li S, Goodwin JS. Effectiveness of COVID-19 Booster on the Risk of Hospitalization Among Medicare Beneficiaries. Mayo Clinic proceedings. 2022;97(10):1780-1793.
[Macchia A, 2022] Macchia A, Ferrante D, Bouzas MB et al. Immunogenicity induced by the use of alternative vaccine platforms to deal with vaccine shortages in a low- to middle-income country: Results of two randomized clinical trials. Lancet Regional Health. Americas. 2022 Macchia A, Ferrante D, Bouzas MB et al. Immunogenicity induced by the use of alternative vaccine platforms to deal with vaccine shortages in a low- to middle-income country: Results of two randomized clinical trials. Lancet Regional Health. Americas. 2022
[Pascuale CA, 2022] Pascuale CA, Varese A, Ojeda DS et al. Immunogenicity and reactogenicity of heterologous immunization against SARS CoV-2 using Sputnik V, ChAdOx1-S, BBIBP-CorV, Ad5-nCoV, and mRNA-1273. Cell reports. Medicine. 2022;:100706. Pascuale CA, Varese A, Ojeda DS et al. Immunogenicity and reactogenicity of heterologous immunization against SARS CoV-2 using Sputnik V, ChAdOx1-S, BBIBP-CorV, Ad5-nCoV, and mRNA-1273. Cell reports. Medicine. 2022;:100706.
[Xuan Ying Poh, 2022] Xuan Ying Poh, Chee Wah Tan, I. Russel Lee et al. Antibody Response of Heterologous vs Homologous mRNA Vaccine Boosters Against the SARS-CoV-2 Omicron Variant: Interim Results from the PRIBIVAC Study, A Randomized Clinical Trial. SSRN. 2022; Xuan Ying Poh, Chee Wah Tan, I. Russel Lee et al. Antibody Response of Heterologous vs Homologous mRNA Vaccine Boosters Against the SARS-CoV-2 Omicron Variant: Interim Results from the PRIBIVAC Study, A Randomized Clinical Trial. SSRN. 2022;
[Jäger M, 2023] Jäger M, Diem G, Sahanic S et al. Immunity of heterologous and homologous boosted or convalescent individuals against Omicron BA.1, BA.2 and BA.4/5 variants. The Journal of infectious diseases. 2023; Jäger M, Diem G, Sahanic S et al. Immunity of heterologous and homologous boosted or convalescent individuals against Omicron BA.1, BA.2 and BA.4/5 variants. The Journal of infectious diseases. 2023;
[Dunkle, L. M., 2023] Dunkle, L. M., Cai, M. R., McKnight, I. et al. Immunogenicity and Safety of NVX-CoV2373 as a Homologous or Heterologous Booster: A Phase 3 Randomized Clinical Trial in Adults. medRxiv. 2023; Dunkle, L. M., Cai, M. R., McKnight, I. et al. Immunogenicity and Safety of NVX-CoV2373 as a Homologous or Heterologous Booster: A Phase 3 Randomized Clinical Trial in Adults. medRxiv. 2023;
[Andrews N, 2022] Andrews N, Stowe J, Kirsebom F et al. Effectiveness of COVID-19 booster vaccines against covid-19 related symptoms, hospitalisation and death in England. Nature medicine. 2022; Andrews N, Stowe J, Kirsebom F et al. Effectiveness of COVID-19 booster vaccines against covid-19 related symptoms, hospitalisation and death in England. Nature medicine. 2022;
[Vivaldi G, 2022] Vivaldi G, Jolliffe DA, Holt H et al. Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT162b2 and after booster vaccination with BNT162b2 or mRNA-1273: A population-based cohort study (COVIDENCE UK). The Lancet reg Vivaldi G, Jolliffe DA, Holt H et al. Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT162b2 and after booster vaccination with BNT162b2 or mRNA-1273: A population-based cohort study (COVIDENCE UK). The Lancet reg
[Stowe J, 2022] Stowe J, Andrews N, Kirsebom F et al. Effectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation, a test negative case-control study. Nature communications. 2022;13(1):5736. Stowe J, Andrews N, Kirsebom F et al. Effectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation, a test negative case-control study. Nature communications. 2022;13(1):5736.
[Nittayasoot N, 2022] Nittayasoot N, Suphanchaimat R, Thammawijaya P et al. Real-World Effectiveness of COVID-19 Vaccines against Severe Outcomes during the Period of Omicron Predominance in Thailand: A Test-Negative Nationwide Case-Control Study. Vaccines. 2022;10(12). Nittayasoot N, Suphanchaimat R, Thammawijaya P et al. Real-World Effectiveness of COVID-19 Vaccines against Severe Outcomes during the Period of Omicron Predominance in Thailand: A Test-Negative Nationwide Case-Control Study. Vaccines. 2022;10(12).
[Kamal SM, 2023] Kamal SM, Naghib MM, Daadour M et al. The Outcome of BNT162b2, ChAdOx1-Sand mRNA-1273 Vaccines and Two Boosters: A Prospective Longitudinal Real-World Study. Viruses. 2023;15(2). Kamal SM, Naghib MM, Daadour M et al. The Outcome of BNT162b2, ChAdOx1-Sand mRNA-1273 Vaccines and Two Boosters: A Prospective Longitudinal Real-World Study. Viruses. 2023;15(2).
[Cheng DR, 2022] Cheng DR, Clothier HJ, Morgan HJ et al. Myocarditis and myopericarditis cases following COVID-19 mRNA vaccines administered to 12-17-year olds in Victoria, Australia. BMJ paediatrics open. 2022;6(1). Cheng DR, Clothier HJ, Morgan HJ et al. Myocarditis and myopericarditis cases following COVID-19 mRNA vaccines administered to 12-17-year olds in Victoria, Australia. BMJ paediatrics open. 2022;6(1).
[Cristina Morciano, 2023] Cristina Morciano, Stefania Spila Alegiani, Francesca Menniti Ippolito et al. Post-marketing active surveillance of Guillan Barré Syndrome following vaccination with anti-COVID-19 vaccines in persons aged >=12 years in Italy: a multi-database self-c Cristina Morciano, Stefania Spila Alegiani, Francesca Menniti Ippolito et al. Post-marketing active surveillance of Guillan Barré Syndrome following vaccination with anti-COVID-19 vaccines in persons aged >=12 years in Italy: a multi-database self-c
[Nakahara A, 2022] Nakahara A, Biggio J, Elmayan A et al. Safety-related outcomes of novel mRNA COVID-19 vaccines in pregnancy. American journal of perinatology. 2022; Nakahara A, Biggio J, Elmayan A et al. Safety-related outcomes of novel mRNA COVID-19 vaccines in pregnancy. American journal of perinatology. 2022;
[Kachikis A, 2022] Kachikis A, Englund JA, Covelli I et al. Analysis of Vaccine Reactions After COVID-19 Vaccine Booster Doses Among Pregnant and Lactating Individuals. JAMA network open. 2022;5(9):e2230495. Kachikis A, Englund JA, Covelli I et al. Analysis of Vaccine Reactions After COVID-19 Vaccine Booster Doses Among Pregnant and Lactating Individuals. JAMA network open. 2022;5(9):e2230495.
[Sadarangani M, 2022] Sadarangani M, Soe P, Shulha HP et al. Safety of COVID-19 vaccines in pregnancy: a Canadian National Vaccine Safety (CANVAS) network cohort study. The Lancet. Infectious diseases. 2022; Sadarangani M, Soe P, Shulha HP et al. Safety of COVID-19 vaccines in pregnancy: a Canadian National Vaccine Safety (CANVAS) network cohort study. The Lancet. Infectious diseases. 2022;
[DeSilva M, 2022] DeSilva M, Haapala J, Vazquez-Benitez G et al. Evaluation of Acute Adverse Events after Covid-19 Vaccination during Pregnancy. The New England journal of medicine. 2022; DeSilva M, Haapala J, Vazquez-Benitez G et al. Evaluation of Acute Adverse Events after Covid-19 Vaccination during Pregnancy. The New England journal of medicine. 2022;
[Mansour O, 2023] Mansour O, Hernandez-Diaz S, Wyszynski DF. mRNA COVID-19 Vaccination Early in Pregnancy and the Risk of Spontaneous Abortion in an International Pregnancy Registry. Pharmacoepidemiology and drug safety. 2023; Mansour O, Hernandez-Diaz S, Wyszynski DF. mRNA COVID-19 Vaccination Early in Pregnancy and the Risk of Spontaneous Abortion in an International Pregnancy Registry. Pharmacoepidemiology and drug safety. 2023;
[Morgan JA, 2023] Morgan JA, Biggio JR, Martin JK et al. Pregnancy Outcomes in Patients After Completion of the mRNA Coronavirus Disease 2019 (COVID-19) Vaccination Series Compared With Unvaccinated Patients. Obstetrics and gynecology. 2023; Morgan JA, Biggio JR, Martin JK et al. Pregnancy Outcomes in Patients After Completion of the mRNA Coronavirus Disease 2019 (COVID-19) Vaccination Series Compared With Unvaccinated Patients. Obstetrics and gynecology. 2023;
[University Hospital, Basel, Switzerland, 2021] University Hospital, Basel, Switzerland. Immunocompromised Swiss Cohorts Based Trial Platform. clinicaltrials.gov. 2021; University Hospital, Basel, Switzerland. Immunocompromised Swiss Cohorts Based Trial Platform. clinicaltrials.gov. 2021;
[National Institute of Allergy and Infectious Diseases (NIAID), 2021] National Institute of Allergy and Infectious Diseases (NIAID). COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders. clinicaltrials.gov. 2021; National Institute of Allergy and Infectious Diseases (NIAID). COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders. clinicaltrials.gov. 2021;
[Medical University of Vienna, 2021] Medical University of Vienna. Single blinded randomized controlled trial on BNT162b2 or mRNA-1273 (mRNA) vs Ad26COVS1 or ChAdOx1-S (viral vector) in kidney transplant recipients without SARS-CoV-2 spike protein antibodies following full vaccination agains Medical University of Vienna. Single blinded randomized controlled trial on BNT162b2 or mRNA-1273 (mRNA) vs Ad26COVS1 or ChAdOx1-S (viral vector) in kidney transplant recipients without SARS-CoV-2 spike protein antibodies following full vaccination agains
[Albalawi OM, 2021] Albalawi OM, Alomran MI, Alsagri GM et al. Analyzing the U.S. Post-marketing safety surveillance of COVID-19 vaccines. Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society. 2021; Albalawi OM, Alomran MI, Alsagri GM et al. Analyzing the U.S. Post-marketing safety surveillance of COVID-19 vaccines. Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society. 2021;
[Taquet M, 2021] Taquet M, Husain M, Geddes JR et al. Cerebral venous thrombosis and portal vein thrombosis: A retrospective cohort study of 537,913 COVID-19 cases. EClinicalMedicine. 2021;39:101061. Taquet M, Husain M, Geddes JR et al. Cerebral venous thrombosis and portal vein thrombosis: A retrospective cohort study of 537,913 COVID-19 cases. EClinicalMedicine. 2021;39:101061.
[Magnus MC, 2021] Magnus MC, Gjessing HK, Eide HN et al. Covid-19 Vaccination during Pregnancy and First-Trimester Miscarriage. The New England journal of medicine. 2021; Magnus MC, Gjessing HK, Eide HN et al. Covid-19 Vaccination during Pregnancy and First-Trimester Miscarriage. The New England journal of medicine. 2021;
[Kharbanda EO, 2021] Kharbanda EO, Haapala J, DeSilva M et al. Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy. JAMA. 2021; Kharbanda EO, Haapala J, DeSilva M et al. Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy. JAMA. 2021;
[Edelman A, 2022] Edelman A, Boniface ER, Benhar E et al. Association Between Menstrual Cycle Length and Coronavirus Disease 2019 (COVID-19) Vaccination: A U.S. Cohort. Obstetrics and gynecology. 2022; Edelman A, Boniface ER, Benhar E et al. Association Between Menstrual Cycle Length and Coronavirus Disease 2019 (COVID-19) Vaccination: A U.S. Cohort. Obstetrics and gynecology. 2022;
[Wesselink AK, 2022] Wesselink AK, Hatch EE, Rothman KJ et al. A prospective cohort study of COVID-19 vaccination, SARS-CoV-2 infection, and fertility. American journal of epidemiology. 2022; Wesselink AK, Hatch EE, Rothman KJ et al. A prospective cohort study of COVID-19 vaccination, SARS-CoV-2 infection, and fertility. American journal of epidemiology. 2022;
[Tu TM, 2022] Tu TM, Yi SJ, Koh JS et al. Incidence of Cerebral Venous Thrombosis Following SARS-CoV-2 Infection vs mRNA SARS-CoV-2 Vaccination in Singapore. JAMA network open. 2022;5(3):e222940. Tu TM, Yi SJ, Koh JS et al. Incidence of Cerebral Venous Thrombosis Following SARS-CoV-2 Infection vs mRNA SARS-CoV-2 Vaccination in Singapore. JAMA network open. 2022;5(3):e222940.
[Gallo K, 2022] Gallo K, Goede A, Mura C et al. A Comparative Analysis of COVID-19 Vaccines Based on over 580,000 Cases from the Vaccination Adverse Event Reporting System. Vaccines. 2022;10(3). Gallo K, Goede A, Mura C et al. A Comparative Analysis of COVID-19 Vaccines Based on over 580,000 Cases from the Vaccination Adverse Event Reporting System. Vaccines. 2022;10(3).
[Goddard K, 2022] Goddard K, Lewis N, Fireman B et al. Risk of myocarditis and pericarditis following BNT162b2 and mRNA-1273 COVID-19 vaccination. Vaccine. 2022; Goddard K, Lewis N, Fireman B et al. Risk of myocarditis and pericarditis following BNT162b2 and mRNA-1273 COVID-19 vaccination. Vaccine. 2022;
[Massari M, 2022] Massari M, Spila Alegiani S, Morciano C et al. Postmarketing active surveillance of myocarditis and pericarditis following vaccination with COVID-19 mRNA vaccines in persons aged 12 to 39 years in Italy: A multi-database, self-controlled case series study Massari M, Spila Alegiani S, Morciano C et al. Postmarketing active surveillance of myocarditis and pericarditis following vaccination with COVID-19 mRNA vaccines in persons aged 12 to 39 years in Italy: A multi-database, self-controlled case series study
[Botton J, 2022] Botton J, Jabagi MJ, Bertrand M et al. Risk for Myocardial Infarction, Stroke, and Pulmonary Embolism Following COVID-19 Vaccines in Adults Younger Than 75 Years in France. Annals of internal medicine. 2022; Botton J, Jabagi MJ, Bertrand M et al. Risk for Myocardial Infarction, Stroke, and Pulmonary Embolism Following COVID-19 Vaccines in Adults Younger Than 75 Years in France. Annals of internal medicine. 2022;
[Fell DB, 2022] Fell DB, Dimanlig-Cruz S, Regan AK et al. Risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy: population based retrospective cohort study. BMJ (Clinical research ed.). 2022;378:e071416. Fell DB, Dimanlig-Cruz S, Regan AK et al. Risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy: population based retrospective cohort study. BMJ (Clinical research ed.). 2022;378:e071416.
[Imai K, 2022] Imai K, Tanaka F, Kawano S et al. Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunisation Stress-related Responses with COVID-19 mRNA Vaccine. The journal of allergy and clinical immunology. In practice. 2022; Imai K, Tanaka F, Kawano S et al. Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunisation Stress-related Responses with COVID-19 mRNA Vaccine. The journal of allergy and clinical immunology. In practice. 2022;
[Wong HL, 2022] Wong HL, Hu M, Zhou CK et al. Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases. Lancet (London, England). 2022;399(10342):2191-2199. Wong HL, Hu M, Zhou CK et al. Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases. Lancet (London, England). 2022;399(10342):2191-2199.
[Simone A, 2022] Simone A, Herald J, Chen A et al. Acute myocarditis following a third dose of COVID-19 mRNA vaccination in adults. International journal of cardiology. 2022; Simone A, Herald J, Chen A et al. Acute myocarditis following a third dose of COVID-19 mRNA vaccination in adults. International journal of cardiology. 2022;
[Lloyd PC, 2022] Lloyd PC, Hu M, Wong HL et al. Near real-time surveillance of safety outcomes in US COVID-19 vaccine recipients aged 12 to 64 years. Vaccine. 2022; Lloyd PC, Hu M, Wong HL et al. Near real-time surveillance of safety outcomes in US COVID-19 vaccine recipients aged 12 to 64 years. Vaccine. 2022;
[Buchan SA, 2022] Buchan SA, Seo CY, Johnson C et al. Epidemiology of Myocarditis and Pericarditis Following mRNA Vaccination by Vaccine Product, Schedule, and Interdose Interval Among Adolescents and Adults in Ontario, Canada. JAMA network open. 2022;5(6):e2218505. Buchan SA, Seo CY, Johnson C et al. Epidemiology of Myocarditis and Pericarditis Following mRNA Vaccination by Vaccine Product, Schedule, and Interdose Interval Among Adolescents and Adults in Ontario, Canada. JAMA network open. 2022;5(6):e2218505.
[Kim JE, 2022] Kim JE, Park J, Min YG et al. Associations of Neuralgic Amyotrophy with COVID-19 Vaccination: Disproportionality Analysis Using the World Health Organization Pharmacovigilance Database. Muscle & nerve. 2022; Kim JE, Park J, Min YG et al. Associations of Neuralgic Amyotrophy with COVID-19 Vaccination: Disproportionality Analysis Using the World Health Organization Pharmacovigilance Database. Muscle & nerve. 2022;
[Calvert C, 2022] Calvert C, Carruthers J, Denny C et al. A population-based matched cohort study of early pregnancy outcomes following COVID-19 vaccination and SARS-CoV-2 infection. Nature communications. 2022;13(1):6124. Calvert C, Carruthers J, Denny C et al. A population-based matched cohort study of early pregnancy outcomes following COVID-19 vaccination and SARS-CoV-2 infection. Nature communications. 2022;13(1):6124.
[Le Vu S, 2022] Le Vu S, Bertrand M, Jabagi MJ et al. Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines. Nature communications. 2022;13(1):3633. Le Vu S, Bertrand M, Jabagi MJ et al. Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines. Nature communications. 2022;13(1):3633.
[Patone M, 2022] Patone M, Mei XW, Handunnetthi L et al. Risk of Myocarditis After Sequential Doses of COVID-19 Vaccine and SARS-CoV-2 Infection by Age and Sex. Circulation. 2022; Patone M, Mei XW, Handunnetthi L et al. Risk of Myocarditis After Sequential Doses of COVID-19 Vaccine and SARS-CoV-2 Infection by Age and Sex. Circulation. 2022;
[Straus W, 2022] Straus W, Urdaneta V, Esposito DB et al. Analysis of Myocarditis Among 252 Million mRNA-1273 Recipients Worldwide. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2022; Straus W, Urdaneta V, Esposito DB et al. Analysis of Myocarditis Among 252 Million mRNA-1273 Recipients Worldwide. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2022;
[Corrao G, 2022] Corrao G, Franchi M, Cereda D et al. Increased risk of myocarditis and pericarditis and reduced likelihood of severe clinical outcomes associated with COVID-19 vaccination: a cohort study in Lombardy, Italy. BMC infectious diseases. 2022;22(1):844. Corrao G, Franchi M, Cereda D et al. Increased risk of myocarditis and pericarditis and reduced likelihood of severe clinical outcomes associated with COVID-19 vaccination: a cohort study in Lombardy, Italy. BMC infectious diseases. 2022;22(1):844.
[Yih WK, 2022] Yih WK, Daley MF, Duffy J et al. A broad assessment of covid-19 vaccine safety using tree-based data-mining in the vaccine safety datalink. Vaccine. 2022; Yih WK, Daley MF, Duffy J et al. A broad assessment of covid-19 vaccine safety using tree-based data-mining in the vaccine safety datalink. Vaccine. 2022;
[Katherine Yih W, 2022] Katherine Yih W, Daley MF, Duffy J et al. Tree-based data mining for safety assessment of first COVID-19 booster doses in the Vaccine Safety Datalink. Vaccine. 2022; Katherine Yih W, Daley MF, Duffy J et al. Tree-based data mining for safety assessment of first COVID-19 booster doses in the Vaccine Safety Datalink. Vaccine. 2022;
[Bots SH, 2022] Bots SH, Riera-Arnau J, Belitser SV et al. Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countr Bots SH, Riera-Arnau J, Belitser SV et al. Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countr
[Lill Trogstad, 2022] Lill Trogstad. Increased Occurrence of Menstrual Disturbances in 18- to 30-Year-Old Women after COVID-19 Vaccination. SSRN. 2022; Lill Trogstad. Increased Occurrence of Menstrual Disturbances in 18- to 30-Year-Old Women after COVID-19 Vaccination. SSRN. 2022;
[Anders Hviid, 2022] Anders Hviid, Tuomo Nieminen, Nicklas Pihlstrom et al. Booster Vaccination with SARS-CoV-2 mRNA Vaccines and Myocarditis Risk in Adolescents and Young Adults: A Nordic Cohort Study of 8.9 Million Residents. medRxiv. 2022; Anders Hviid, Tuomo Nieminen, Nicklas Pihlstrom et al. Booster Vaccination with SARS-CoV-2 mRNA Vaccines and Myocarditis Risk in Adolescents and Young Adults: A Nordic Cohort Study of 8.9 Million Residents. medRxiv. 2022;
[Xu S, 2022] Xu S, Huang R, Sy LS et al. A safety study evaluating non-COVID-19 mortality risk following COVID-19 vaccination. Vaccine. 2022; Xu S, Huang R, Sy LS et al. A safety study evaluating non-COVID-19 mortality risk following COVID-19 vaccination. Vaccine. 2022;
[Hanson KE, 2022] Hanson KE, Goddard K, Lewis N et al. Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink. JAMA network open. 2022;5(4):e228879. Hanson KE, Goddard K, Lewis N et al. Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink. JAMA network open. 2022;5(4):e228879.
[Walker JL, 2022] Walker JL, Schultze A, Tazare J et al. Safety of COVID-19 vaccination and acute neurological events: A self-controlled case series in England using the OpenSAFELY platform. Vaccine. 2022; Walker JL, Schultze A, Tazare J et al. Safety of COVID-19 vaccination and acute neurological events: A self-controlled case series in England using the OpenSAFELY platform. Vaccine. 2022;
[Tsang RS, 2023] Tsang RS, Joy M, Byford R et al. Adverse events following first and second dose COVID-19 vaccination in England, October 2020 to September 2021: a national vaccine surveillance platform self-controlled case series study. Euro surveillance : bulletin Europ Tsang RS, Joy M, Byford R et al. Adverse events following first and second dose COVID-19 vaccination in England, October 2020 to September 2021: a national vaccine surveillance platform self-controlled case series study. Euro surveillance : bulletin Europ
[Abara WE, 2023] Abara WE, Gee J, Marquez P et al. Reports of Guillain-Barré Syndrome After COVID-19 Vaccination in the United States. JAMA network open. 2023;6(2):e2253845. Abara WE, Gee J, Marquez P et al. Reports of Guillain-Barré Syndrome After COVID-19 Vaccination in the United States. JAMA network open. 2023;6(2):e2253845.
[Fadi Nahab, 2023] Fadi Nahab, Rana Bayakly, Mary Elizabeth Sexton et al. Factors Associated with Stroke after COVID-19 Vaccination: A Statewide Analysis. medRxiv. 2023; Fadi Nahab, Rana Bayakly, Mary Elizabeth Sexton et al. Factors Associated with Stroke after COVID-19 Vaccination: A Statewide Analysis. medRxiv. 2023;
[Su WJ, 2023] Su WJ, Liu YL, Chang CH et al. Risk of myocarditis and pericarditis following coronavirus disease 2019 messenger RNA Vaccination-A nationwide study. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi. 2023; Su WJ, Liu YL, Chang CH et al. Risk of myocarditis and pericarditis following coronavirus disease 2019 messenger RNA Vaccination-A nationwide study. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi. 2023;
[Duijster JW, 2023] Duijster JW, Lieber T, Pacelli S et al. Sex-disaggregated outcomes of adverse events after COVID-19 vaccination: A Dutch cohort study and review of the literature. Frontiers in immunology. 2023;14:1078736. Duijster JW, Lieber T, Pacelli S et al. Sex-disaggregated outcomes of adverse events after COVID-19 vaccination: A Dutch cohort study and review of the literature. Frontiers in immunology. 2023;14:1078736.
[Kim HJ, 2023] Kim HJ, Lee SJ, Sa S et al. Safety of COVID-19 Vaccines among Patients with Type 2 Diabetes Mellitus: Real-World Data Analysis. Diabetes & metabolism journal. 2023; Kim HJ, Lee SJ, Sa S et al. Safety of COVID-19 Vaccines among Patients with Type 2 Diabetes Mellitus: Real-World Data Analysis. Diabetes & metabolism journal. 2023;
[Pawlowski C, 2021] Pawlowski C, Rincón-Hekking J, Awasthi S et al. Cerebral Venous Sinus Thrombosis is not Significantly Linked to COVID-19 Vaccines or Non-COVID Vaccines in a Large Multi-State Health System. Journal of stroke and cerebrovascular diseases : the official jou Pawlowski C, Rincón-Hekking J, Awasthi S et al. Cerebral Venous Sinus Thrombosis is not Significantly Linked to COVID-19 Vaccines or Non-COVID Vaccines in a Large Multi-State Health System. Journal of stroke and cerebrovascular diseases : the official jou
[Pushkar Aggarwal, 2021] Pushkar Aggarwal. Pharmacovigilance Analysis on Cerebrovascular Accidents and Coronavirus disease 2019 Vaccines. medRxiv. 2021; Pushkar Aggarwal. Pharmacovigilance Analysis on Cerebrovascular Accidents and Coronavirus disease 2019 Vaccines. medRxiv. 2021;
[Zhao H., 2021] Zhao H., Anger J.T., Souders C. et al. Low Rates of Urologic Side Effects Following Coronavirus Disease Vaccination: An Analysis of the Food and Drug Administration Vaccine Adverse Event Reporting System. Urology. 2021; Zhao H., Anger J.T., Souders C. et al. Low Rates of Urologic Side Effects Following Coronavirus Disease Vaccination: An Analysis of the Food and Drug Administration Vaccine Adverse Event Reporting System. Urology. 2021;
[Schulz JB, 2021] Schulz JB, Berlit P, Diener HC et al. COVID-19 vaccine-associated cerebral venous thrombosis in Germany. Annals of neurology. 2021; Schulz JB, Berlit P, Diener HC et al. COVID-19 vaccine-associated cerebral venous thrombosis in Germany. Annals of neurology. 2021;
[David Presby, 2021] David Presby, Emily Capodilupo. Objective and Subjective COVID-19 Vaccine Reactogenicity by Age and Vaccine Manufacturer. medRxiv. 2021; David Presby, Emily Capodilupo. Objective and Subjective COVID-19 Vaccine Reactogenicity by Age and Vaccine Manufacturer. medRxiv. 2021;
[Gee J, 2021] Gee J, Marquez P, Su J et al. First Month of COVID-19 Vaccine Safety Monitoring - United States, December 14, 2020-January 13, 2021. MMWR. Morbidity and mortality weekly report. 2021;70(8):283-288. Gee J, Marquez P, Su J et al. First Month of COVID-19 Vaccine Safety Monitoring - United States, December 14, 2020-January 13, 2021. MMWR. Morbidity and mortality weekly report. 2021;70(8):283-288.
[Shimabukuro TT, 2021] Shimabukuro TT, Kim SY, Myers TR et al. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. The New England journal of medicine. 2021;384(24):2373-2382. Shimabukuro TT, Kim SY, Myers TR et al. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. The New England journal of medicine. 2021;384(24):2373-2382.
[Abbattista M, 2021] Abbattista M, Martinelli I, Peyvandi F. Comparison of adverse drug reactions among four COVID-19 vaccines in Europe using the EudraVigilance database: thrombosis at unusual sites. Journal of thrombosis and haemostasis : JTH. 2021; Abbattista M, Martinelli I, Peyvandi F. Comparison of adverse drug reactions among four COVID-19 vaccines in Europe using the EudraVigilance database: thrombosis at unusual sites. Journal of thrombosis and haemostasis : JTH. 2021;
[Naim Ouldali, 2022] Naim Ouldali, Haleh Bagheri, Francesco Salvo et al. Multisystemic inflammatory syndrome following COVID-19 mRNA vaccine in children: a national post-authorization pharmacovigilance study. medRxiv. 2022; Naim Ouldali, Haleh Bagheri, Francesco Salvo et al. Multisystemic inflammatory syndrome following COVID-19 mRNA vaccine in children: a national post-authorization pharmacovigilance study. medRxiv. 2022;
[Oster ME, 2022] Oster ME, Shay DK, Su JR et al. Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021. JAMA. 2022;327(4):331-340. Oster ME, Shay DK, Su JR et al. Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021. JAMA. 2022;327(4):331-340.
[Kitagawa H, 2022] Kitagawa H, Kaiki Y, Sugiyama A et al. Adverse reactions to the BNT162b2 and mRNA-1273 mRNA COVID-19 vaccines in Japan. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2022; Kitagawa H, Kaiki Y, Sugiyama A et al. Adverse reactions to the BNT162b2 and mRNA-1273 mRNA COVID-19 vaccines in Japan. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2022;
[Rolfes L, 2022] Rolfes L, Härmark L, Kant A et al. COVID-19 vaccine reactogenicity - A cohort event monitoring study in the Netherlands using patient reported outcomes. Vaccine. 2022; Rolfes L, Härmark L, Kant A et al. COVID-19 vaccine reactogenicity - A cohort event monitoring study in the Netherlands using patient reported outcomes. Vaccine. 2022;
[Marco Massari, 2022] Marco Massari, Stefania Spila-Alegiani, Cristina Morciano et al. Post-marketing active surveillance of myocarditis and pericarditis following vaccination with COVID-19 mRNA vaccines in persons aged 12-39 years in Italy: a multi-database, self-controlled c Marco Massari, Stefania Spila-Alegiani, Cristina Morciano et al. Post-marketing active surveillance of myocarditis and pericarditis following vaccination with COVID-19 mRNA vaccines in persons aged 12-39 years in Italy: a multi-database, self-controlled c
[Kant A, 2022] Kant A, Jansen J, van Balveren L et al. Description of Frequencies of Reported Adverse Events Following Immunization Among Four Different COVID-19 Vaccine Brands. Drug safety. 2022; Kant A, Jansen J, van Balveren L et al. Description of Frequencies of Reported Adverse Events Following Immunization Among Four Different COVID-19 Vaccine Brands. Drug safety. 2022;
[Nguyen S, 2022] Nguyen S, Bastien E, Chretien B et al. Transverse myelitis following SARS-CoV-2 vaccination: a pharmacoepidemiological study in the World Health Organization's database. Annals of neurology. 2022; Nguyen S, Bastien E, Chretien B et al. Transverse myelitis following SARS-CoV-2 vaccination: a pharmacoepidemiological study in the World Health Organization's database. Annals of neurology. 2022;
[Toledo-Salinas C, 2022] Toledo-Salinas C, Scheffler-Mendoza SC, Castano-Jaramillo LM et al. Anaphylaxis to SARS-CoV-2 Vaccines in the Setting of a Nationwide Passive Epidemiological Surveillance Program. Journal of clinical immunology. 2022; Toledo-Salinas C, Scheffler-Mendoza SC, Castano-Jaramillo LM et al. Anaphylaxis to SARS-CoV-2 Vaccines in the Setting of a Nationwide Passive Epidemiological Surveillance Program. Journal of clinical immunology. 2022;
[Mascolo A, 2022] Mascolo A, di Mauro G, Fraenza F et al. Maternal, fetal and neonatal outcomes among pregnant women receiving COVID-19 vaccination: The preg-co-vax study. Frontiers in immunology. 2022;13:965171. Mascolo A, di Mauro G, Fraenza F et al. Maternal, fetal and neonatal outcomes among pregnant women receiving COVID-19 vaccination: The preg-co-vax study. Frontiers in immunology. 2022;13:965171.
[García-Grimshaw M, 2022] García-Grimshaw M, Galnares-Olalde JA, Bello-Chavolla OY et al. Incidence of Guillain-Barré syndrome following SARS-CoV-2 immunization: Analysis of a nationwide registry of recipients of 81 million doses of seven vaccines. European journal of neurology. 2 García-Grimshaw M, Galnares-Olalde JA, Bello-Chavolla OY et al. Incidence of Guillain-Barré syndrome following SARS-CoV-2 immunization: Analysis of a nationwide registry of recipients of 81 million doses of seven vaccines. European journal of neurology. 2
[Naveed Z, 2022] Naveed Z, Li J, Wilton J et al. Comparative Risk of Myocarditis/Pericarditis Following Second Doses of BNT162b2 and mRNA-1273 Coronavirus Vaccines. Journal of the American College of Cardiology. 2022;80(20):1900-1908. Naveed Z, Li J, Wilton J et al. Comparative Risk of Myocarditis/Pericarditis Following Second Doses of BNT162b2 and mRNA-1273 Coronavirus Vaccines. Journal of the American College of Cardiology. 2022;80(20):1900-1908.
[Jacobs JW, 2022] Jacobs JW, Booth GS, Guarente J et al. Autoimmune haemolytic anaemia and immune thrombocytopenia following SARS-CoV-2 and non-SARS-CoV-2 vaccination: 32?Years of passive surveillance data. British journal of haematology. 2022; Jacobs JW, Booth GS, Guarente J et al. Autoimmune haemolytic anaemia and immune thrombocytopenia following SARS-CoV-2 and non-SARS-CoV-2 vaccination: 32?Years of passive surveillance data. British journal of haematology. 2022;
[Gallo AT, 2022] Gallo AT, Scanlon L, Clifford J et al. Immediate Adverse Events Following COVID-19 Vaccination in Australian Pharmacies: A Retrospective Review. Vaccines. 2022;10(12). Gallo AT, Scanlon L, Clifford J et al. Immediate Adverse Events Following COVID-19 Vaccination in Australian Pharmacies: A Retrospective Review. Vaccines. 2022;10(12).
[Kajiwara S, 2023] Kajiwara S, Akiyama N, Baba H et al. Association between COVID-19 vaccines and the menstrual cycle in young Japanese women. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2023; Kajiwara S, Akiyama N, Baba H et al. Association between COVID-19 vaccines and the menstrual cycle in young Japanese women. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2023;
[WHO, 2022] WHO. Statement for healthcare professionals: How COVID-19 vaccines are regulated for safety and effectiveness (Revised March 2022). WHO - Reports. 2022; WHO. Statement for healthcare professionals: How COVID-19 vaccines are regulated for safety and effectiveness (Revised March 2022). WHO - Reports. 2022;
[WHO, 2022] WHO. Coronavirus disease (COVID-19): Vaccines safety. World Health Organization - Q&A. 2022;(February). WHO. Coronavirus disease (COVID-19): Vaccines safety. World Health Organization - Q&A. 2022;(February).
[World Health Organization, 2021] World Health Organization. Safety of COVID-19 Vaccines. World Health Organization (WHO). 2021; World Health Organization. Safety of COVID-19 Vaccines. World Health Organization (WHO). 2021;
[Organización Mundial de la Salud, 2022] Organización Mundial de la Salud. Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19. WHO - News. 2022; Organización Mundial de la Salud. Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19. WHO - News. 2022;