Moderna COVID-19 vaccine

Extended version of the vaccine

Moderna COVID-19 vaccine

Authorization

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 over [WHO, 2021 ].
SAGE/WHO Recommendation: Authorized for emergency use in individuals aged 18 years and over [WHO, 2021 ].

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 over [EMA , 2021 ].
23 July 2021: For individuals from 12 to 17 years of age [EMA, 2021 ].

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 over [MINISTERIO DE SALUD DE ARGENTINA, 2021 ].

Brazilian Health Regulatory Agency (ANVISA, Brazil)
Not authorized.

Health Canada
Authorized for emergency use on 23 December 2020 [Health Canada, 2020 ].

Public Health Institute (ISP, Chile)
Not authorized.

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 over [INVIMA, 2021 ].

Center for the State Control of Drug Quality (CECMED, Cuba)
Not authorized.

U.S. Food and Drug Administration (FDA)
Authorized for emergency use.
18 December 2020: For individuals 18 years of age and over [Moderna, Inc, 2020 ].

Federal Commission for the Protection against Sanitary Risk (COFEPRIS, Mexico)
Authorized for emergency use on 18 August 2021 [Gobierno de México, 2021 ].

Authorization in other jurisdictions in the Americas
Guatemala
Honduras
Saint Vincent and the Grenadines
Curaçao
Guyana
Haiti
Honduras
Paraguay
Puerto Rico
Saba
San Martin
Sint Eustatius

Authorization in other jurisdictions
Listed by alphabetical order
Andorra
Australia
Austria
Bangladesh
Belgium
Bhutan
Botswana
Brunei
Bulgaria
Congo
Croatia
Cyprus
Czechia
Denmark
Estonia
Faroe Islands
Fiji
Finland
France
Germany
Ghana
Greece
Greenland
Hungary
Iceland
India
Indonesia
Israel
Italy
Japan
Kenya
Kuwait
Latvia
Libya
Liechtenstein
Lithuania
Luxembourg
Malaysia
Maldives
Malta
Micronesia
Mongolia
Netherlands
Nigeria
Norway
Palestine
Pakistan
Philippines
Poland
Portugal
Qatar
Romania
Saudi Arabia
Seychelles
Singapore
Slovakia
Slovenia
South Korea
Spain
Sri Lanka
Sweden
Switzerland
Taiwan
Thailand
United Arab Emirates
UK
Vietnam
West Bank

The Emergency Use Authorization does not constitute marketing authorization in the country.

Manufacturing

Manufacturer

Drug substance [World Health Organization, 2020 ]
Moderna TX, Inc, an American company based in Cambridge and in the United States.

Lonza Group manufactures the vaccine at facilities in Portsmouth, New Hampshire in the United States and in Visp in Switzerland. Four manufacturing facilities are planned, each capable of producing an estimated 100 million doses per year [MODERNA TX INC. & LONZA SALES LTD, 2020 ].

Other manufacturers

Drug Product [World Health Organization, 2020 ]
Rovi Pharma Industrial Services, S.A company based in Spain are the main manufacturers of Moderna COVID-19 vaccine, they have several alliances for manufacturing contractors of the product.

Catalent is a company headquartered in Somerset, New Jersey. It provides vial filling and packaging [Rick Mullin, 2021 ].

Baxter Pharmaceutical Solutions, is a company located in the United States, it produces the drug product of the vaccine.

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.

 

Dosage form and ingredients

The dosage form is a dispersion for intramuscular injection that is provided in a multidose vial (vial: 10 doses of 0.5 mL, total 5 mL per vial).

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
Lipids
SM-102 (proprietary to Moderna)
Polyethylene glycol (PEG) 2000-dimyristoyl glycerol (DMG)
1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)
Cholesterol
Salts, sugars and buffers
Tromethamine (Synonyms: trometamol,tromethamin,Tris, tris(hydroxymethyl)aminomethane)
Tromethamine hydrochloride (Synonyms: Tris hydrochloride; Tris chloride; Tris(hydroxymethyl)aminomethane hydrochloride)
Acetic acid
Sodium acetate trihydrate
Sucrose
Water for injections
Moderna COVID-19 vaccine is preservative-free.

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

Countries that have not yet achieved high vaccine coverage rates in the high-priority groups who are experiencing a high incidence of COVID-19 cases combined with vaccine supply constraints, WHO recommends that such countries should focus on achieving a high first dose coverage in the high priority groups by extending the inter-dose interval up to 12 weeks [WHO, 2021 ].

Dose-finding studies

mRNA-1273-P201 was a dose-finding, randomized, phase 2 trial sponsored by ModernaTX, Inc. and conducted in The United States between 22 May 2020 and 08 July 2020. It was registered with the trial registry number NCT04405076. The trial included healthy participants ≥18 years with a body mass index of 18 kg/m2–30 kg/m2. The sample size was 600 (2 cohorts of 300). The mean age of the participants was 37.4 years in cohort 1 (≥18 - <55 years) and 64.3 years in cohort 2 (≥55 years) and the proportion of females was 61%. Participants were randomly assigned in a 1:1:1 ratio to receive Moderna COVID-19 vaccine 50 µg, 100 µg or placebo. The vaccine induced binding antibodies and neutralizing antibodies by 28 days post-vaccination one that were higher at the 100 µg dose relative to the 50 µg dose but the difference was less apparent post-vaccination two. Binding antibodies and neutralizing antibodies increased substantially by 14 days following the second vaccination (day 43) to levels exceeding those of convalescent sera and remained elevated through day 57 [Chu L, 2021 ].

No hay datos disponibles sobre la intercambiabilidad de la vacuna de Moderna contra el COVID-19 con otras vacunas COVID-19 para completar la serie de vacunación [WHO, 2021 ].

There is no evidence yet about the effects of the coadministration of Moderna COVID-19 vaccine with other vaccines included in routine vaccination programs [WHO, 2021 ].

Indications and contraindications

Indications

Moderna COVID-19 vaccine is indicated for individuals 12 years of age and over [WHO, 2021 ],[EMA, 2021 ].

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, 2021 ]. (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, 2021 ].

Precautions

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. Such persons should be observed for 30 minutes after vaccination [WHO, 2021 ].

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 [WHO, 2021 ].

Severe allergic reaction (e.g., anaphylaxis) to an injectable medication.

A possible causal association with very rare cases of myocarditis in young men (16−24 years of age) is currently being investigated [WHO, 2021 ].

Adverse events reports suggest an increased risk of myocarditis and pericarditis, particularly following the second dose and onset of symptoms within a few days after vaccination. Vaccinated individuals should be instructed to seek immediate medical attention if they develop the following symptoms: chest pain, shortness of breath, or feelings of having fluttering after vaccination [FDA, 2021 ].

Vaccination should be postponed in individuals suffering from acute severe febrile illness, or acute infection.

The available data on COVID-19 Vaccine Moderna vaccination of pregnant females are insufficient to assess vaccine efficacy in pregnancy since no clinical trial evaluating vaccines to prevent COVID-19 has included pregnant females.

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, 2021 ].

The interaction of concomitant administration of COVID-19 Vaccine Moderna with other vaccines has not been studied.

There should be a minimum interval of 14 days between the administration of this vaccine with any other vaccine in the immunization schedule, until data on co-administration with other vaccines are available [WHO, 2021 ].

Vaccination may be offered regardless of a person’s history of symptomatic or asymptomatic SARS-CoV-2 infection [World Health Organization, 2021 ].

Although there are currently no medical contraindications on the vaccinating of a person with COVID-19, it is recommended to defer all vaccinations until complete recovery [PAHO, 2020 ].

Although there are currently no contraindications on the vaccinating of a person who has had contact with a COVID-19 case, it is recommended to defer vaccination until the quarantine has been completed (14 days after the last exposure) [PAHO, 2020 ].

Close observation for at least 30 minutes is recommended following vaccination.

Clinical studies - general characteristics

Randomized trials

COVE (an acronym for: Coronavirus Efficacy and Safety Study) or study P301 was a phase 3 randomized clinical trial sponsored by ModernaTX, Inc. and conducted The United States between July 27, 2020, and October 23, 2020. It was registered with trial registry number NCT04470427. The trial included participants 18 years of age or older with no known history of SARS-CoV-2 infection and with circumstances that put them at an appreciable risk of SARS-CoV-2 infection, a high risk of severe COVID-19, or both. The sample size was 30420. The mean age of the participants was 51.4 years and the proportion of females was 47.3%. Participants were randomly assigned in a 1:1 ratio to receive Moderna COVID-19 vaccine or placebo vaccine. The intervention was administered as a sterile liquid at a concentration of 0.2 mg per milliliter and administered by injection into the deltoid muscle according to a two-dose regimen. Injections were given 28 days apart, in the same arm, in a volume of 0.5 ml containing 100 µg of mRNA-1273 or saline placebo. Vaccine mRNA-1273 was stored at 2° to 8°C (35.6° to 46.4°F) at clinical sites before preparation and vaccination. No dilution was required. Doses could be held in syringes for up to 8 hours at room temperature before administration [Baden LR, 2021 ].

TeenCove was a phase 2-3, randomized, placebo-controlled trial sponsored by ModernaTX, Inc and conducted United States between December 2020 to June 2022. It was registered with trial registry number NCT04649151. The trial included healthy male and female adolescents between the ages of 12 and 17 years. The sample size was 3732. The mean age of the participants was 14.3 years and the proportion of women was 49%. Participants were randomly assigned in a 2:1 ratio to receive mRNA-1273 (2489 participants) or placebo (1243 participants). The intervention was administered as two injections of either mRNA-1273 vaccine (each injection containing 100 µg, for a total dose of 200 µg) or placebo (saline solution), 28 days apart [Ali K, 2021 ].

Hall VG et al was an ongoing 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 ].

COV-BOOST was a blinded, multicentre, randomized, controlled, phase 2 trial sponsored by University Hospital Southampton NHS Foundation Trust and conducted in United Kingdom between May 2021 - August 2022. It was registered with ISRCTN73765130. The trial included adults aged 30 years or older, in good physical health (mild to moderate well-controlled comorbidities were permitted), who had received two doses of either Pfizer or AstraZeneca COVID-19 vaccine. The sample size was 2883. The median age of ChAd/ChAd-primed group was 53 years in the younger age group and 76 years in the older age group. In the BNT/BNT-primed group, the median age was 51 years in the younger age group and 78 years in the older age group. The proportion of females was 46.7% in the ChAd/ChAD-primed and 53.6% in BNT/BNT-primed group. Participants were randomly assigned in a 1:1:1:1 ratio in group A, 1:1:1:1:1 in group B, and 1:1:1:1 in Group C to receive an experimental vaccine or control. The intervention was administered as:

  1. Group A received NVX-CoV2373( Novavax), a half dose of NVX, AstraZeneca, or control quadrivalent meningococcal conjugate vaccine (MenACWY).
  2. Group B received Pfizer, VLA2001 (Valneva), a half dose of VLA, Ad26.COV2.S (Janssen) or MenACWY .
  3. Group C received mRNA1273 (Moderna), CVnCov (CureVac), a half dose of BNT, or MenACWY [Munro, Alasdair P S, 2021 ].



Ongoing randomized trials

MOSAIC is an ongoing phase 2, randomized trial (registered with the number NCT04894435 [Canadian Immunization Research Network, 2021 ]) sponsored by Canadian Immunization Research Network that is being conducted in Canada. It was first registered in May 2021 and plans to enroll 1200 healthy adults with mild or moderate stable comorbidities of 18 years of age and older. Participants will receive two different vaccines (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) for first and second doses, as well as for differing intervals between the first and second dose of the vaccines. It is expected to run until March 2023.

ARNCOMBI is an ongoing multicenter, randomized, open-label trial (registered with the number NCT04900467 [Assistance Publique - Hôpitaux de Paris, 2021 ]) sponsored by Assistance Publique - Hôpitaux de Paris that is being conducted in France. It was first registered in May 2021 and plans to enroll 400 patients aged 18 years and older that will receive a regimen of vaccines combining Pfizer-BioNTech or Moderna . It is expected to run until January 2022.

VATICO is an ongoing open-label, randomized trial (phase 4) (registered with the number NCT04969250 [International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), 2021 ]) sponsored by International Network for Strategic Initiatives in Global HIV Trials that is being conducted in United States, Denmark, Greece, India, Nigeria, Poland, Singapore, Spain, Switzerland, Uganda, and United Kingdom. It was first registered in July 2021 and plans to enroll 640 participants of the ACTIV-3/TICO clinical trial (NCT04501978) that will receive Moderna mRNA-1273 or the Pfizer BNT162b2 vaccine. It is expected to run until July 2022.

Guerrerio PA et al is an ongoing randomized, placebo-controlled crossover study (phase 2) (registered with the number NCT04977479 [National Institute of Allergy and Infectious Diseases (NIAID), 2021 ]) sponsored by National Institute of Allergy and Infectious Diseases (NIAID) that is being conducted in The United States. It was first registered in July 2021 and plans to enroll 100 people aged 18-69 that will receive Pfizer-BioNTech COVID-19 vaccine and one dose of placebo on different days. It is expected to run until December 2022.

Boost-TX is an ongoing phase 2, randomized, single blinded study (registered with the number 2021-002927-39 [Medical University of Vienna, 2021 ]) sponsored by Medical University of Vienna that is being conducted in Austria. It was first registered in May 2021 and plans to enroll 200 kidney transplant recipients that will receive BNT162b2 or mRNA-1273 (mRNA) vaccines. End of trial: Date not available.

mRNA-1283-P101 is an ongoing phase 1, randomized, observer-blind, dose-ranging study (registered with the number ClinicalTrials.gov number NCT04813796 [ModernaTX, Inc., 2021 ]) sponsored by ModernaTX, Inc that is being conducted in United States. It was first registered in March 2021 and plans to enroll 125 healthy adults aged 18-55 years that will receive mRNA-1283 and mRNA-1273 SARS-CoV-2 Vaccine. It is expected to run until April 2022.

mRNA-1273-D3-2021 is an ongoing phase 4, randomized controlled trial (registered with the number ClinicalTrials.gov number NCT04677660 [Mark Loeb, 2021 ]) sponsored by Mark Loeb that is being conducted in Canada. It was first registered in July 2021 and plans to enroll 414 vaccinated residents ≥65 years that will receive a third dose of mRNA-1273 (Moderna COVID-19) vaccine. It is expected to run until April 2022.

QHD00028 is an ongoing phase 2, open-label study (registered with the number NCT04969276 [Sanofi Pasteur, a Sanofi Company, 2021 ]) sponsored by Sanofi Pasteur, a Sanofi Company that is being conducted in United States. It was first registered in July 2021 and plans to enroll 300 fully vaccinated adults with mRNA-1273 65 years of age and older that will receive a dose of Fluzone High-Dose Quadrivalent vaccine and a booster dose of Moderna COVID-19 Vaccine, administered concomitantly or singly. It is expected to run until January 2022.

Deepali Kumar et al is an ongoing phase 4, randomized, double-blind, placebo-controlled trial (registered with the number NCT04885907 [University Health Network, Toronto, 2021 ]) sponsored by University Health Network, Toronto that is being conducted in Canada. It was first registered in May 2021 and plans to enroll 120 fully vaccinated adults with mRNA-1273 18 years of age and older that will receive a third dose of the mRNA-1273 vaccine or saline placebo. It is expected to run until August 2021.

COVERALL is an ongoing phase 3, multicenter randomized controlled, open-label, 2-arm sub-study pilot trial (registered with the number NCT04805125 [University Hospital, Basel, Switzerland, 2021 ]) sponsored by University Hospital, Basel that is being conducted in Switzerland. It was first registered in March 2021 and plans to enroll 431 patients included in the Swiss HIV Cohort Study or the Swiss Transplant Cohort Study that will receive mRNA vaccine Comirnaty (Pfizer / BioNTech) or the Covid-19 mRNA Vaccine Moderna. It is expected to run until July 2022.

SWITCH is an ongoing multicenter, randomized, single-blind, controlled trial (registered with the number ClinicalTrials.gov number NCT04927936 [Erasmus Medical Center, 2021 ]) sponsored by Erasmus Medical Center that is being conducted in Netherlands. It was first registered in June 2021 and plans to enroll 432 health care workers aged 18 to 65 years vaccinated once with Janssen vaccine that will receive Janssen vaccine (homologous boosting); Moderna vaccine (heterologous boosting);or Pfizer vaccine (heterologous boosting). It is expected to run until September 2022.

CoVPN 3006 is an ongoing phase 3, randomized clinical trial (registered with the number ClinicalTrials.gov number NCT04811664 [National Institute of Allergy and Infectious Diseases (NIAID), 2021 ]) sponsored by National Institute of Allergy and Infectious Diseases that is being conducted in United States. It was first registered in March 2021 and plans to enroll 37500 adults aged 18-29 that will receive Moderna COVID-19 vaccine against SARS-CoV-2 infection. It is expected to run until December 2021.

21-0002 is an ongoing phase 1 trial, open-label, randomized (registered with the number ClinicalTrials.gov number NCT04785144 [National Institute of Allergy and Infectious Diseases (NIAID), 2021 ]) sponsored by National Institute of Allergy and Infectious Diseases that is being conducted in United States. It was first registered in March 2021 and plans to enroll 135 naïve and previously vaccinated adults 18 years of age and older that will receive SARS-CoV-2 Variant Vaccine (mRNA-1273.351). It is expected to run until August 2022.

DAIT ACV01 is an ongoing randomized, multi-site, adaptive, open-label clinical trial (registered with the number ClinicalTrials.gov number NCT05000216 [National Institute of Allergy and Infectious Diseases (NIAID), 2021 ]) sponsored by National Institute of Allergy and Infectious Diseases (NIAID) that is being conducted in the United States. It was first registered in August 2021 and plans to enroll 600 participants with autoimmune diseases requiring immunosuppressive medications, that will receive different COVID-19 vaccines booster doses (Moderna, Pfizer-BioNTech or Janssen COVID-19 vaccine) to compare the immune response in the participants. It is expected to run until December 2022.

TAK-919-1501 is an ongoing phase 1 and 2, randomized, observer-blind, placebo-controlled trial (registered with the number ClinicalTrials.gov number NCT04677660 [Takeda, 2021 ]) sponsored by Takeda that is being conducted in Japan. It was first registered in December 2020 and plans to enroll 200 healthy adults aged 20 years and older that will receive TAK-919 vaccine. It is expected to run until March 2022.

IMCOVAS is a randomized ongoing trial (registered with the number EudraCT Number 2021-001993-52 [University of Antwerp, 2021 ]) sponsored by University of Antwerp that is being conducted in Belgium. It was first registered in May 2021 and plans to enroll 840 healthy volunteer adults, the study will assess the humoral immune response against SARS-Cov-2 infection of different vaccines and adapted vaccine schedules in comparison with the reference schedules. It is expected to run until a date not yet available.

The P204 trial (mRNA-1273-P204) (NCT04796896) is an ongoing RCTs that will assess efficacy of Moderna COVID-19 vaccine in children and adolescents (for more information see -Efficacy of the vaccine in subgroups-).

Other studies providing efficacy or safety data

20-0003 (expansion in older adults) was a phase 1, non-randomized study sponsored by National Institute of Allergy and Infectious Diseases (NIAID) and conducted in the United States of America at Kaiser Permanente Washington Health Research Institute in Seattle, the Emory University School of Medicine in Atlanta, and the National Institute of Allergy and Infectious Diseases Vaccine Research Center in Bethesda, Maryland between April 16 and May 12, 2020. It was registered with ClinicalTrials.gov number NCT04283461 [National Institute of Allergy and Infectious Diseases (NIAID), 2020 ].
This trial was expanded to include participants older than 56 years [Anderson EJ, 2020 ].
The sample size was 40. The mean age of the participants was 68.7 years and the proportion of females was 53%.
All the participants were assigned sequentially to receive two doses of either 25 µg or 100 µg of vaccine administered 28 days apart.

The ICARUS-IBD study, was a cohort study, that enroll individuals with inflammatory bowel disease receiving the vaccine (for more information see -Efficacy of the vaccine in subgroups-) [Serre-Yu Wong, 2021 ].

Gee et al. (CDC report) was a safety monitoring non-comparative study conducted in United states. The study enrolled 13,794,904 vaccine doses (Pfizer or Moderna) participants that received Moderna COVID-19 vaccine. Based on data from Vaccine Adverse Event Reporting System and the v-safe system between 14 December 2020 and 13 January 2021.

HEROES-RECOVER was a prospective cohort study conducted in United states. The study enrolled 5,716 (3,964 unvaccinated, 1,754 vaccinated) participants that received Moderna COVID-19 vaccine. Based on data from HEROES-RECOVER cohorts between December 14, 2020 to April 10 2021.

Flacco et al. was a retrospective cohort study conducted in Italy. The study enrolled 2,020 participants that received Moderna COVID-19 vaccine. 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.

Khan et al. was a retrospective cohort study conducted in United states. The study enrolled 3,380 older adults with inflammatory bowel disease participants that received Moderna COVID-19 vaccine. Based on data from the Veterans Health Administration (VHA) between December 18 2020 to April 20 2021.

Pawlowski C et al. was a retrospective cohort study conducted in United States. The study enrolled 16,471 participants that received Moderna COVID-19 vaccine. Based on data from the Mayo Clinic health system between December 1 2020 and April 20 2021.

Desai AP et al. (CDC report) was a safety monitoring non-comparative study conducted in United States. The study enrolled 3,203 participants that received Moderna COVID-19 vaccine. Based on data from Vaccine Adverse Event Reporting System and the v-safe system between December 14 2020 through February 5 2021.

Shimabukuro et al. (CDC report) was a safety monitoring non-comparative study conducted in United States. The study enrolled 16,439 (pregnant persons) pregnant persons that received Moderna or Pfizer COVID-19 vaccine. Based on data from Vaccine Adverse Event Reporting System and the v-safe system from December 14 2020 to February 28, 2021.

Andrejko et al. was a case-control study conducted in United States . The study enrolled 1,023 participants that received Moderna COVID-19 vaccine. Based on data from California Department of Public Health via a web-based reporting system from 24 February to 29 April 2021.

Malinis et al. was a cross-sectional study conducted in United States. The study enrolled 557 (solid organ transplant recipients) participants that received Moderna COVID-19 vaccine. Based on data from Yale New Haven Hospital on May 18, 2021.

Chung 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. Based on data from a test-negative design study among patients who had symptoms consistent with covid-19 between 14 December 2020 and 19 April 2021.

Pawlowski C et al. was a retrospective study conducted in United States. The study enrolled 266,094 participants (36,352 Moderna doses). Based on data from the Mayo Clinic health system between January 1 2017 and March 15, 2021.

Tarke A et al. was an immunogenicity study conducted in United States. The study enrolled 30 general population that received Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) vaccines.

Alisa Fox et al. was a cohort conducted in United States. The study enrolled 50 Lactating females (Twenty-three participants had received Pfizer vaccine, 14 had received Moderna vaccine, and 13 had received J&J vaccine). Fifty pairs of milk samples were obtained from vaccine recipients within 1 week before vaccination and 14 days (Pfizer/Moderna) or 28 days (J&J) after completion of the vaccine regimen.

Omar M Albalawi et al. was a retrospective database analysis study conducted in United States. The study enrolled the General population that received Pfizer-BioNTech, Moderna, and Janssen Ad26.COV2.S vaccines. This retrospective analysis was conducted using the publically available database of the U.S. Vaccine Adverse Event Reporting System (VAERS). VAERS is a critical component of the national passive surveillance (spontaneous reporting) system of the approved vaccines in the U.S

Other ongoing studies

ANTICOV is an ongoing observational study (registered with the number ClinicalTrials.gov number NCT04878796 [Azienda Socio Sanitaria Territoriale di Cremona, 2021 ]) sponsored by Azienda Socio Sanitaria Territoriale di Cremona that is being conducted in Italy. It was first registered in May 2021 and plans to enroll 300 cancer patients aged 18 years and older receiving active therapy or who have completed their oncologic treatment within 6 months, that will assess vaccine efficacy on patients who received BNT162b2 (Pfizer) and mRNA-1273 (Moderna). It is expected to run until May 2022.

Gurbel PA et al is an ongoing non-randomized study (registered with the number NCT04910971 [LifeBridge Health, 2021 ]) sponsored by LifeBridge Health that is being conducted in United States. It was first registered in June 2021 and plans to enroll 60 COVID-19 vaccinated health care workers that received Pfizer/BioNTech or Moderna vaccine. It is expected to run until July 2022.

Covid-19-Abs is an ongoing non-randomized study (registered with the number NCT04944095 [Dr. Sidney J. Stohs, 2021 ]) sponsored by Dr. Sidney J. Stohs that is being conducted in United States. It was first registered in June 2021 and plans to enroll 10000 residents and staff associated with nursing homes, extended care facilities, and over-55 communities that received Pfizer, Moderna, or J &J COVID-19 vaccines. It is expected to run until December 2022.

CoVEHPI is an ongoing cohort study (registered with the number NCT04709003 [Clalit Health Services, 2020 ]) sponsored by Clalit Health Services that is being conducted in Israel. It was first registered in January 2021 and plans to enroll 4504 healthcare workers aged 18 years and older that received Pfizer or Moderna COVID-19 vaccine. It is expected to run until June 2022.

McKelvey JL et al is an ongoing non-randomized study (registered with the number NCT04852289 [National Institute on Aging (NIA), 2021 ]) sponsored by National Institute on Aging that is being conducted in United States. It was first registered in April 2021 and plans to enroll 160 healthy individuals over 18 years of age that will receive Pfizer or Moderna COVID-19 vaccines. It is expected to run until March 2024.

Friis-Hansen L et al is an ongoing non-randomized study (registered with the number NCT04842305 [Lenanrt Friis-Hansen, 2021 ]) sponsored by Lenanrt Friis-Hansen that is being conducted in Denmark. It was first registered in April 2021 and plans to enroll 500 SARS-COV-2 Naïve persons, COVID-19 convalescents, and vaccinated with Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, or AstraZeneca ChAdOx1-S vaccine. It is expected to run until March 2024.

21-0012 is an ongoing phase 1/2, non-randomized study (registered with the number NCT04889209 [National Institute of Allergy and Infectious Diseases (NIAID), 2021 ]) sponsored by National Institute of Allergy and Infectious Diseases that is being conducted in United States. It was first registered in May 2021 and plans to enroll 550 vaccinated healthy individuals 18 years of age and older that will receive a delayed booster dose of Ad26.COV2.S or mRNA-1273 vaccine. It is expected to run until May 2025.

IROC is an ongoing non-randomized study (registered with the number NCT04930055 [Indiana University, 2021 ]) sponsored by Indiana University that is being conducted in United States. It was first registered in June 2021 and plans to enroll 240 cancer patients 18 years of age and older receiving BTN162b2, mRNA-1273, or Ad26.COV2.S. It is expected to run until August 2023.

LymphVAX is an ongoing non-randomized study (registered with the number NCT04872738 [Massachusetts General Hospital, 2021 ]) sponsored by Massachusetts General Hospital that is being conducted in United States. It was first registered in May 2021 and plans to enroll 2000 women with a history of breast cancer that received Moderna or Pfizer COVID-19 vaccines. It is expected to run until December 2022.

VIOLA is an ongoing non-randomized study (registered with the number NCT04843774 [NYU Langone Health, 2021 ]) sponsored by NYU Langone Health that is being conducted in United States. It was first registered in April 2021 and plans to enroll 60 Multiple Sclerosis patients treated with Ocrelizumab that received Moderna or Pfizer COVID-19 vaccines. It is expected to run until October 2022.

Bahl A et al is an ongoing non-randomized study (registered with the number NCT04912700 [William Beaumont Hospitals, 2021 ]) sponsored by William Beaumont Hospitals that is being conducted in United States. It was first registered in June 2021 and plans to enroll 11834 patients with COVID-19 who presented to Beaumont Health emergency departments. It is expected to run until June 2021.

VAX4FRAIL is an ongoing non-randomized study (registered with the number NCT04848493 [Azienda Unità Sanitaria Locale Reggio Emilia, 2021 ]) sponsored by Azienda Unità Sanitaria Locale Reggio Emilia that is being conducted in Italy. It was first registered in April 2021 and plans to enroll 1300 frail subjects with impaired immuno-competence that received Pfizer-BioNTech or Moderna vaccines. It is expected to run until April 2022.

mRNA-1273-P903 is an ongoing non-randomized study (registered with the number NCT04958954 [ModernaTX, Inc., 2021 ]) sponsored by ModernaTX, Inc that is being conducted in United States. It was first registered in July 2021 and plans to enroll 50000000 adults 18 years of age and older that received SARS-CoV-2 mRNA-1273 vaccine. It is expected to run until June 2023.

CPAT is an ongoing non-randomized study (registered with the number NCT04969263 [National Institute of Allergy and Infectious Diseases (NIAID), 2021 ]) sponsored by National Institute of Allergy and Infectious Diseases (NIAID) that is being conducted in United States. It was first registered in July 2021 and plans to enroll 200 kidney transplant recipients that will receive a third dose of the same vaccine as the prior two doses (Moderna COVID-19 vaccine or Pfizer-BioNTech COVID-19 vaccine). It is expected to run until October 2022.

US-TYS-11909 is an ongoing cohort, non-randomized study (registered with the number NCT04834401 [St. Barnabas Medical Center, 2021 ]) sponsored by St. Barnabas Medical Center that is being conducted in United States. It was first registered in April 2021 and plans to enroll 120 people with multiple sclerosis aged 18 to 65 years that will receive Moderna COVID-19 vaccine. It is expected to run until April 2023.

COVIAAD is an ongoing non-randomized study (registered with the number NCT04806113 [McGill University Health Centre/Research Institute of the McGill University Health Centre, 2021 ]) sponsored by McGill University Health Centre/Research Institute of the McGill University Health Centre that is being conducted in Canada. It was first registered in March 2021 and plans to enroll 220 patients with rheumatic diseases that will receive mRNA-1273 vaccine. The time between dose 1 and dose 2 of the vaccine will be 28 days. It is expected to run until June 2022.

000115-C is an ongoing non-randomized study (registered with the number NCT04847050 [National Cancer Institute (NCI), 2021 ]) sponsored by National Cancer Institute (NCI) that is being conducted in United States. It was first registered in April 2021 and plans to enroll 120 adults 18 years of age and older with solid tumors or blood cancer that will receive a dose of mRNA-1273 on day 1 and day 29. It is expected to run until February 2023.

mRNA-1273-P205 is an ongoing phase 2/3, non-randomized study (registered with the number NCT04927065 [ModernaTX, Inc., 2021 ]) sponsored by ModernaTX, Inc that is being conducted in United States. It was first registered in June 2021 and plans to enroll 896 fully vaccinated adults with mRNA-1273 that will receive a single booster dose of mRNA-1273.211. It is expected to run until July 2022.

mRNA-1273-P304 is an ongoing phase 3b, open-label, non-randomized study (registered with the number NCT04860297 [ModernaTX, Inc., 2021 ]) sponsored by ModernaTX, Inc that is being conducted in United States. It was first registered in April 2021 and plans to enroll 240 adult solid organ transplant recipients and healthy controls that will receive mRNA-1273 vaccine. It is expected to run until March 2023.

NL73618.100.20 is an ongoing phase 4, non-randomized study (registered with the number 2021-001202-30 [Diakonessenhuis, 2021 ]) sponsored by Diakonessenhuis that is being conducted in Netherlands. It was first registered in April 2021 and plans to enroll 400 adults 18 years of age and older that received Pfizer, Moderna, AstraZeneca, or Janssen COVID-19 vaccine. End of study: Date not available.

R10933-10987-COV-2118 is an ongoing phase 2 randomized, open-label, parallel-group study (registered with the number NCT04852978 [Regeneron Pharmaceuticals, 2021 ]) sponsored by Regeneron Pharmaceuticals that is being conducted in United States. It was first registered in April 2021 and plans to enroll 180 healthy adult volunteers that will receive Moderna mRNA-1273 vaccine administered with Casirivimab+Imdevimab. It is expected to run until August 2022.

CoviCompareM is an ongoing phase 2, comparative, non-randomized study (registered with the number NCT04748471 [Assistance Publique - Hôpitaux de Paris, 2021 ]) sponsored by Assistance Publique - Hôpitaux de Paris that is being conducted in France. It was first registered in February 2021 and plans to enroll 180 volunteers 18-75 years of age that will receive Moderna vaccine. It is expected to run until January 2023.

PNR-1475 is an ongoing cohort study (registered with the number NCT04892888 [Takeda, 2021 ]) sponsored by Takeda that is being conducted in Japan. It was first registered in May 2021 and plans to enroll 1000 subjects with underlying disease considered to be at high risk for a severe illness that received mRNA-1273 vaccine. It is expected to run until February 2022.

COVATRANS is an ongoing cohort study (registered with the number NCT04828460 [University Hospital, Strasbourg, France, 2021 ]) sponsored by University Hospital, Strasbourg that is being conducted in France. It was first registered in April 2021 and plans to enroll 3500 kidney transplant recipients aged 15 years and older who receive Pfizer, Moderna, and Astra-Zeneca vaccines. It is expected to run until February 2023.

VAX-TRES is an ongoing phase 2, non-randomized study (registered with the number NCT04930770 [Maria Joyera Rodríguez, 2021 ]) sponsored by Maria Joyera Rodríguez that is being conducted in Spain. It was first registered in June 2021 and plans to enroll 80 patients with renal transplants that will receive a third dose of mRNA-1273 vaccine. It is expected to run until March 2022.

Deepak Sahasrabudhe et al is an ongoing non-randomized study (registered with the number NCT04854980 [University of Rochester, 2021 ]) sponsored by University of Rochester that is being conducted in United States. It was first registered in April 2021 and plans to enroll 55 cancer patients 50 to 75 years of age that received both doses of mRNA-1273 vaccine. It is expected to run until July 2022.

PNR-1474 is an ongoing cohort study (registered with the number NCT04941144 [Takeda, 2021 ]) sponsored by Takeda that is being conducted in Japan. It was first registered in June 2021 and plans to enroll 20000 individuals who have participated in the preceding cohort study that received Moderna COVID-19 vaccine. It is expected to run until December 2022.

mRNA-1273-P902 is an ongoing cohort study (registered with the number NCT04958304 [ModernaTX, Inc., 2021 ]) sponsored by ModernaTX, Inc that is being conducted in United States. It was first registered in July 2021 and plans to enroll 1000 pregnancies in females exposed to the Moderna COVID-19 vaccine (mRNA-1273) during pregnancy. It is expected to run until January 2024.

CVG01 is an ongoing non-randomized study (registered with the number 2021-001769-19 [GUVAX (Gothenburg University Vaccine Research Institute), 2021 ]) sponsored by GUVAX that is being conducted in Sweden. It was first registered in March 2021 and plans to enroll 1200 immune-competent subjects and patients with primary or secondary immune deficiency aged 18 years and older that received Moderna vaccine. End of study: Date not available.

COVID-19-004 (NCT04796896) is an ongoing phase 2, randomized trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). It was first registered in February 21, 2021 and plans to enroll 3400 participants with one population including individuals with a history of allergic reactions or Mast Cell Disorder (HA/MCD) and one non-atopic population, finalizing in June 2021. Participants will be randomized to receive Moderna COVID-19 Vaccine, Pfizer-BioNTech COVID-19 Vaccine or placebo [National Institute of Allergy and Infectious Diseases (NIAID), 2021 ].

COVAC-IC is an ongoing prospective observational study (registered with the number NCT04805216 [University Hospitals of North Midlands NHS Trust, 2021 ]) sponsored by University Hospitals of North Midlands NHS Trust that is being conducted in the United Kingdom. It was first registered in March 18, 2021 and plans to enroll 80 immunosuppressed participants with hematological conditions that will receive several COVID-19 vaccines including Moderna COVID-19 Vaccine. It is expected to run until November 15, 2021.

Methods used to assess efficacy

In the COVE trial [Baden LR, 2021 ], the primary endpoint was specified as efficacy against symptomatic Covid-19 at least 14 days after the second dose among participants who were seronegative at trial entry. End points were judged by an independent adjudication committee that was unaware of group assignment.

COVID-19 cases were defined as occurring in participants who had at least two of the following symptoms: fever (temperature ≥38°C), chills, myalgia, headache, sore throat, or new olfactory or taste disorder, or as occurring in those who had at least one respiratory sign or symptom (including cough, shortness of breath, or clinical or radiographic evidence of pneumonia) and at least one nasopharyngeal swab, nasal swab, or saliva sample (or respiratory sample, if the participant was hospitalized) that was positive for SARS-CoV-2 by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) test. Participants were assessed for the presence of SARS-CoV-2-binding antibodies specific to the SARS-CoV-2 nucleocapsid protein (Roche Elecsys, Roche Diagnostics International) and had a nasopharyngeal swab for SARS-CoV-2 RT-PCR testing (Viracor, Eurofins Clinical Diagnostics) before each injection. SARS-CoV-2-infected volunteers were followed daily, to assess symptom severity, for 14 days or until symptoms resolved, whichever was longer. A nasopharyngeal swab for RT-PCR testing and a blood sample for identifying serologic evidence of SARS-CoV-2 infection were collected from participants with symptoms of COVID-19.

Safety evaluation methods

Safety assessments included: Solicited local adverse events; solicited systemic adverse events; unsolicited adverse reactions; adverse events leading to discontinuation from a dose; adverse events leading to discontinuation from participation in the trial; medically attended adverse events; serious adverse events.

End points were judged by an independent adjudication committee that was unaware of group assignment.

Vaccine efficacy and effectiveness

Efficacy of preclinical studies on the vaccine

The capacity to induce protective immune responses against an infectious pathogen by a directly injected, non-replicating mRNA had been previously demonstrated for other pathogens [Petsch B, 2012 ]

Direct preclinical evidence of immune response induced by Moderna COVID-19 Vaccine came from one study in nonhuman primates that received 10 or 100 µg of the vaccine or no vaccine [Corbett KS, 2020 ]. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2 and active viral replication and viral genomes in bronchoalveolar-lavage fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. The vaccination induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung.

Mutations of mRNA sequence of SARS-CoV-2, such as E484K, N501Y or K417N, can potentially reduce vaccine-elicited response. The evidence on these and other variants is still evolving but mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy [Wang Z, 2021 ].

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.

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

Main efficacy outcomes of Moderna COVID-19 vaccine

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.

Contracting COVID-19 after the first dose (measured at least 14 days after the first injection)

The relative risk of contracting COVID-19 after the first dose (>14 days) 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 after the first dose (>14 days) by 93%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19 after the first dose (>14 days). Comparison: Moderna COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 782 people not receiving Moderna COVID-19 vaccine out of 14164 presented this outcome (52 per 1000) versus 58 out of 14287 in the group that did receive it (4 per 1000). In other words, 48 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 4.8%, or that the intervention reduced the risk of contracting COVID-19 after the first dose (>14 days) by 4.8 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 21. Which means that 21 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.

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 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 0.05 (95% CI 0 to 1). This means Moderna COVID-19 vaccine reduced the risk of Contracting COVID-19 after second dose (12-17y) by 95%, 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 high.

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% (14,372 out of 30,346 participants) [El Sahly HM, 2021 ].

The relative risk of contracting COVID-19 in men in the group that received the Moderna COVID-19 vaccine versus the group that received the placebo vaccine was 0.08 (95% CI 0.06 to 0.12). This means the Moderna COVID-19 vaccine reduced the risk of contracting COVID-19 in men by 92%, compared with the placebo vaccine.

The relative risk of contracting COVID-19 in women in the group that received the Moderna COVID-19 vaccine versus the group that received the placebo vaccine was 0.07 (95% CI 0.04 to 0.1). This means the Moderna COVID-19 vaccine reduced the risk of contracting COVID-19 in women by 93%, compared with the 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% (7,512 out of 30,351 participants) [El Sahly HM, 2021 ].

The relative risk of Contracting COVID-19 (>65y) in the group that received the Moderna COVID-19 vaccine versus the group that received the 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 the placebo vaccine.

The relative risk of Contracting COVID-19 (>75y) in the group that received the Moderna COVID-19 vaccine versus the group that received the 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 the 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 ].


Non-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 primary CD4 type 1 helper T responses. There is no evidence that indicates a lower efficacy in older adults. It is important to notice that there were very few patients >80 years old included.

 
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 ].

P204 study (mRNA-1273-P204) is an ongoing phase 2/3, randomized trial sponsored by ModernaTX, Inc. It was first registered on 15 March 2021 and plans to enroll 6750 participants with children between 6 months of age and less than 12 years of age, finalizing on 10 June 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 ].

 

Obesity

Randomized trials

The proportion of participants with severe obesity (Body Mass Index >30) in the COVE trial was 7% (2,046 out of 30,351 participants) [Baden LR, 2021 ].

A post-hoc analysis similarly demonstrated comparable efficacy in participants with obesity (95.8%, CI 95% 82.6- to 99.0%) versus no high-risk comorbidity (94.0%, CI 95% 83.5- to 97.8%) [FDA, 2020 ].

Some researchers have hypothesized, drawing on evidence of immune cell dysregulation and alterations in inflammatory signaling pathways, that these vaccines would offer reduced protection in obesity due to a weakened immune response, [Popkin BM, 2020 ]. Even though the COVE trial was not powered to detect differences between subgroups, the magnitude of the effect was similar between the subgroups, and there was no statistical evidence of a subgroup effect by race and ethnic group.

 
Pregnancy

Randomized trials

The available data are insufficient to assess vaccine efficacy since no clinical trial has included this group.

Non-comparative studies

The cohort study mRNA-1273-P902 is currently evaluating the efficacy/safety of the vaccine in pregnancy in females exposed to the Moderna COVID-19 vaccine (mRNA-1273) during pregnancy [ModernaTX, Inc., 2021 ].

 

Breast-feeding

Randomized trials

The available data are insufficient to assess vaccine efficacy since no clinical trial has included this group.


Non-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 a 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 that 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 compared to both 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 [Alisa Fox, 2021 ].

 

Immunocompromised persons

Randomized trials

Available data are currently insufficient to assess efficacy in persons with conditions compromising immunity since no clinical trial has included this group.

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 ].

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 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 phase 3b, open-label, non-randomized study mRNA-1273-P304 is currently evaluating the efficacy/safety of the vaccine in adult solid organ transplant recipients and healthy controls [ModernaTX, Inc., 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 ].

Non-comparative studies

ICARUS-IBD was a cohort study conducted in the United States (sample size = 48, including 25 receiving Moderna COVID-19 Vaccine). The study evaluated individuals with inflammatory bowel disease receiving biologics who completed two-dose vaccine schedules and found high levels of seroconversion [Serre-Yu Wong, 2021 ].

The prospective observational study COVAC-IC is currently evaluating the immune response to Covid-19 vaccines in immunosuppressed participants with hematological conditions [University Hospitals of North Midlands NHS Trust, 2021 ].

The observational study ANTICOV is currently evaluating the effectiveness of COVID-19 mRNA vaccines Pfizer and Moderna in cancer patients aged 18 years and older receiving active therapy or who have completed their oncologic treatment within 6 months [Azienda Socio Sanitaria Territoriale di Cremona, 2021 ].

The non-randomized study IROC is currently evaluating the efficacy/safety of the vaccine in cancer patients 18 years of age and older [Indiana University, 2021 ].

The non-randomized study VIOLA is currently evaluating the immune response of the Pfizer-BioNTech and Moderna messenger RNA (mRNA)-platform vaccines in Multiple Sclerosis patients treated with Ocrelizumab [NYU Langone Health, 2021 ].

The non-randomized study VAX4FRAIL is currently evaluating the efficacy/safety of the vaccine in frail subjects with impaired immuno-competence [Azienda Unità Sanitaria Locale Reggio Emilia, 2021 ].
The non-randomized study CPAT is currently evaluating the efficacy/safety of the vaccine in kidney transplant recipients [National Institute of Allergy and Infectious Diseases (NIAID), 2021 ].

The cohort, non-randomized study US-TYS-11909 is currently evaluating the efficacy/safety of the vaccine in people with multiple sclerosis aged 18 to 65 years [St. Barnabas Medical Center, 2021 ].

The non-randomized study COVIAAD is currently evaluating the efficacy/safety of the vaccine in patients with rheumatic diseases [McGill University Health Centre/Research Institute of the McGill University Health Centre, 2021 ].

The non-randomized study 000115-C is currently evaluating the efficacy/safety of the vaccine in adults 18 years of age and older with solid tumors or blood cancer [National Cancer Institute (NCI), 2021 ].

The phase 2, non-randomized study VAX-TRES is currently evaluating the efficacy/safety of the vaccine in patient with renal transplants [Maria Joyera Rodríguez, 2021 ].

The non-randomized study Deepak Sahasrabudhe et al is currently evaluating the efficacy/safety of the vaccine in cancer patients 50 to 75 years of age [University of Rochester, 2021 ].

The non-randomized study CVG01 is currently evaluating the efficacy/safety of the vaccine in immune competent subjects and patients with primary or secondary immune deficiency aged 18 years and older [GUVAX (Gothenburg University Vaccine Research Institute), 2021 ].

 

Persons living with HIV

Randomized trials

The proportion of participants with HIV in the COVE trial was 0.6% (179 out of 30,351 participants) [Baden LR, 2021 ].
There were no reported differences in efficacy among the clinical trial participants with well-controlled HIV. Available data are currently insufficient to evaluate efficacy for persons living with HIV who are not well controlled on therapy.

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 ].

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 ].

 
Persons with recent COVID-19

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 infections.

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.

According to the researchers, these findings open the discussion about changing vaccination policy to deliver only a single dose to individuals with recent SARS-CoV-2 infection that may free up additional doses for individuals that have no preexisting immunity to the virus. However, no country is using the previous infection as a criterion to decide who should receive the vaccine and how.

Other data on vaccine efficacy and effectiveness

Main effectiveness outcomes of Moderna COVID-19 vaccine (Other studies)

Contracting COVID-19

Chung 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. Based on data from a test negative design study among patients who had symptoms consistent with COVID-19 between 14 December 2020 and 19 April 2021. Results showed vaccine effectiveness of 95% (95% CI 88% to 98%). [Chung H, 2021 ].

HEROES-RECOVER was a prospective cohort study conducted in United states. The study enrolled 3,975 participants: 3,179 vaccine; 796 Control. Based on data from HEROES-RECOVER cohorts between December 14, 2020 to April 10 2021. Result showed vaccine effectiveness of 84% (95% CI 31% to 96%) and infection rate of 0.26%/3.93% (vaccinated/unvaccinated) [Thompson MG, 2021 ].

Flacco et al. was 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 ].

Khan et al. was a retrospective cohort study conducted in United states. The study enrolled 14,697 participants (older adults with inflammatory bowel disease). Based on data from the Veterans Health Administration (VHA) between December 18 2020 to April 20 2021. Results showed infection rate 0.12%/1.34% (vaccinated/unvaccinated) [Khan N, 2021 ].

Pawlowski C et al. was a retrospective cohort study conducted in 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 97.3%) and infection rate 0.014%/ 0.19% (vaccinated/unvaccinated) [Pawlowski C, 2021 ]. Andrejko et al. was a case-control study conducted in United States. The study enrolled 1,023 participants: 525 vaccine; 498 Control. Based on data from California Department of Public Health via a web-based reporting system from 24 February to 29 April 2021. Results showed vaccine effectiveness of 85.6% (95% CI 69.1% to 94%) [Kristin Andrejko, 2021 ].

Andrejko et al. was a case-control study conducted in United States. The study enrolled 1,023 participants: 525 Vaccine; 498 Control. Based on data from California Department of Public Health via a web-based reporting system from 24 February to 29 April 2021. Results showed vaccine effectiveness of 85.6% (95% CI 69.1% to 94%) [Kristin Andrejko, 2021 ].

Pilishvili T et al. was a case-control study conducted in United States. The study enrolled 4,931 participants: 1,482 Vaccine group; 3,449 Control group. Based on a test-negative case–control study involving health care personnel across 25 U.S. states, between December 28, 2020 and May 19, 2021. Outcome was measured starting at ≥ 14 days after vaccination. Results showed a vaccine effectiveness of 96.3% (95%CI 91.3 to 98.4) [Pilishvili T, 2021 ]


Contracting severe COVID-19

Khan et al. was a retrospective cohort study conducted in United states. The study enrolled 14,697 participants (older adults with inflammatory bowel disease). Based on data from the Veterans Health Administration (VHA) between December 18 2020 to April 20 2021. Results showed severe infection rate 0.06% /0.32% (vaccinated/unvaccinated) [Khan N, 2021 ].

Pawlowski C et al. was a retrospective cohort study conducted in 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 ].


Transmission
 

No studies reported or assessed this outcome.

 

SARS-CoV-2 variants

Immunogenicity outcomes

Shen et al. was a non-comparative study (neutralizing capacity from recipients' sera) conducted in UK and Denmark. The study included 40 healthy adults, including data from 11 samples from 29 days post first inoculation and 29 samples from 28 days post-second inoculation (day 57). The study showed that the Alpha variant (B.1.1.7) remains sensitive to neutralization, (reduction in neutralizing capacity: 2-fold), by serum samples from convalescent individuals and recipients of an mRNA vaccine (mRNA-1273, Moderna). [Shen X, 2021 ].

Wang et al. was a non-comparative study (neutralizing capacity from recipients' sera) conducted in the United States. The study included 12 healthy adults and data were obtained from blood collected from patients on day 43 (after two doses; days 0 and 28; of vaccine). The study showed that the Alpha variant (B.1.1.7) is refractory to neutralization by most single and combination monoclonal antibody (mAbs) to the N-terminal domain (NTD) of spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). [Wang, P., 2021 ].

Venkata V et al. was a non-comparative study (neutralization capacity of receptor sera) carried out in the United States. The study included 14 healthy adults and data were obtained from blood drawn from patients on day 43 (after two doses; days 0 and 28; of vaccine). The study reported that both infection-induced and vaccine-induced antibodies were effective in neutralizing SARS-CoV-2 variant B.1.1.7 [Venkata Viswanadh Edara, 2021 ].

Wang P et al. was a non-comparative study (neutralization capacity of receptor sera) carried out in the United States. The study included 12 vaccine recipients and data were obtained from blood samples collected on day 43, from the 12 vaccine recipients who received two doses, on days 0 and 28. They reported that B.1.1.7 is refractory to neutralization by most monoclonal antibodies (mAbs) to the N-terminal domain (NTD) of spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinated serum [Wang, P., 2021 ].

Randomized trials

Currently there are no randomized trials that assess vaccine efficacy against SARS-CoV-2 variants.

Other studies

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 ].

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 ].

 

Booster dose

Immunogenicity outcomes

Benotmane I et al. was a non-comparative study conducted in France. The study included 159 participants (kidney transplant). ​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 an ongoing 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 ].

Tobudic S 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 ].

 

Heterologous vaccine regimens

Immunogenicity outcomes

Currently there are no studies that have assessed the vaccine immunogenicity outcomes on a heterologous regimen.

 

Heterologous-booster regimens

Immunogenicity outcomes

Tobudic S 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 et al. 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 ].

Safety of the vaccine

Safety of the vaccine in preclinical studies

Risk of DNA modification or infection
The mRNA platform is by definition a non-infectious, non-integrating platform. So, there is no potential risk of infection or insertional mutagenesis. The mRNA component from the vaccine does not enter the nucleus of the cell and does not affect or interact with a person’s DNA. The mRNA is quickly degraded by normal cellular processes [Pardi N, 2018 ].

 

mRNA vaccine pharmacology
Naked mRNA is quickly degraded by extracellular RNase and is not internalized efficiently [Tsui NB, 2002 ].

Several modifications of the mRNA and delivery method [ Kauffman KJ, 2016 ],[Guan S, 2017 ] have been introduced to regulate degradation of mRNA by normal cellular processes, facilitate integration and promote translation, including:
The mRNA is assembled using pseudouridine, a nucleoside variant naturally occurring in the body that reduces the response of dendritic cells, interferon-associated genes and other components of the immune system to trigger an inflammatory response. [Karikó K, 2008 ].

The use of sequence-engineered mRNA avoids using chemical nucleoside modifications to obtain sufficient protein expression and avoid activation of the innate immune system [Thess A, 2015 ].

The purification of the mRNA component with high performance liquid chromatography results in mRNA that does not induce an inflammatory response and is translated at 10- to 1000-fold greater levels in primary cells [Karikó K, 2011 ].

Mutations of mRNA sequence of SARS-CoV-2, such as E484K, N501Y or K417N, can potentially reduce vaccine-elicited response. The evidence on these and other variants is still evolving but mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy [Wang Z, 2021 ].

 

Reproductive toxicity
A study performed in rats assessing postnatal reproductive toxicity of 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

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.

Main safety outcomes of Moderna COVID-19 vaccine

Any adverse event after the 1st dose (within 7 days after injection)

The relative risk of any adverse event after the 1st dose in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 1.83 (95% CI 1.79 to 1.86). This means Moderna COVID-19 vaccine increased the risk of any adverse event after the 1st dose by 83%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: any adverse event after the 1st dose. Comparison: Moderna COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 7285 people not receiving Moderna COVID-19 vaccine out of 7285 presented this outcome (494 per 1000) versus 13317 out of 15166 in the group that did receive it (902 per 1000). In other words, 408 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 40.8%, or that the intervention increased the risk of any adverse event after the 1st dose by 40.8 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 NNTH is 2. Which means that 2 people need to receive the vaccine for one of them to experienced any adverse event after the 1st dose.

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 (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 2.15 (95% CI 2.11 to 2.19). This means Moderna COVID-19 vaccine increased the risk of any adverse event after the 2nd dose by 115%, 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 (944 per 1000). In other words, 505 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 50.5%, or that the intervention increased the risk of any adverse event after the 2nd dose by 50.5 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 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 1st dose (within 7 days after 1st injection)

The relative risk of local adverse events after the 1st dose in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 4.24 (95% CI 4.1 to 4.38). This means Moderna COVID-19 vaccine increased the risk of local adverse events after the 1st dose by 324%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: local adverse events after the 1st dose. Comparison: Moderna COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 3009 people not receiving Moderna COVID-19 vaccine out of 3009 presented this outcome (211 per 1000) versus 12765 out of 15166 in the group that did receive it (894 per 1000). In other words, 683 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 68.3%, or that the intervention increased the risk of local adverse events after the 1st dose by 68.3 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 1. Which means that 1 people need to receive the vaccine for one of them to experienced local adverse events after the 1st 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 4.69 (95% CI 4.53 to 4.85). This means Moderna COVID-19 vaccine increased the risk of local adverse events after the 2nd dose by 369%, 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 (938 per 1000). In other words, 738 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 73.8%, or that the intervention increased the risk of local adverse events after the 2nd dose by 73.8 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 NNTH is 1. Which means that 1 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 1st dose (within 7 days after injection)

The relative risk of systemic adverse events after the 1st dose in the group that received Moderna COVID-19 vaccine versus the group that received placebo vaccine was 4.24 (95% CI 4.1 to 4.38). This means Moderna COVID-19 vaccine increased the risk of systemic adverse events after the 1st dose by 324%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: systemic adverse events after the 1st dose. Comparison: Moderna COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 3009 people not receiving Moderna COVID-19 vaccine out of 15151 presented this outcome (190 per 1000) versus 12765 out of 15166 in the group that did receive it (805 per 1000). In other words, 615 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 61.5%, or that the intervention increased the risk of systemic adverse events after the 1st dose by 61.5 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 NNTH is 2. Which means that 2 people need to receive the vaccine for one of them to experienced systemic adverse events after the 1st 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 2.17 (95% CI 2.12 to 2.22). This means Moderna COVID-19 vaccine increased the risk of systemic adverse events after the 2nd dose by 117%, 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 (742 per 1000). In other words, 400 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 40%, or that the intervention increased the risk of systemic adverse events after the 2nd dose by 40 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 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% (14,366 out of 30,351 participants) [Baden LR, 2021 ].
Safety profile of Moderna COVID-19 vaccine was similar across sex groups.


Older patients

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 ].

 

Pregnancy

Randomized trials

One study is collecting outcomes for all reported pregnancies that occur after vaccination or were undetected prior to the trial. Through December 2, 2020, 13 pregnancies were reported (6 vaccine group and 7 in the placebo). Unsolicited AEs related to pregnancy included a case of spontaneous abortion and a case of elective abortion, both in the placebo group. However, pregnancy outcomes are still unknown at this time [FDA, 2020 ]

Non-comparative studies

An analysis of the CDC v-safe COVID-19 Pregnancy Registry in 19,252 pregnant persons who received the vaccine did not show obvious safety signals [Shimabukuro TT, 2021 ].

Shimabukuro et al. (CDC report) was a safety monitoring non-comparative study that enrolled 16,439 pregnant women that received Moderna or Pfizer COVID-19 vaccine. Results showed that the most frequent local and systemic reactions wer: 95.6% injection-site pain, 80.6% fatigue, 65.0% headache, 46.0% fever or felt feverish. Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported (Data based on 827 participants in the v-safe pregnancy registry who received an mRNA Covid-19 vaccine, BNT162b2 or mRNA-1273). Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases) [Shimabukuro TT, 2021 ].

The cohort study mRNA-1273-P902 is currently evaluating the efficacy/safety of the vaccine in pregnancy in females exposed to the Moderna COVID-19 vaccine (mRNA-1273) during pregnancy [ModernaTX, Inc., 2021 ].

 

Breast-feeding

Randomized trials

No clinical trial evaluating vaccines to prevent COVID-19 has included breast-feeding females.

 

Persons/ individuals with comorbidities


Randomized trial

The comorbidities studied in clinical trials include hypertension, diabetes, asthma, pulmonary disease, liver disease, kidney disease, infection with human immunodeficiency virus (HIV), hepatitis C virus and hepatitis B virus.


Non-comparative studies

The cohort, non-randomized study US-TYS-11909 is currently evaluating the efficacy/safety of the vaccine in people with multiple sclerosis aged 18 to 65 years [St. Barnabas Medical Center, 2021 ].

 

Immunocompromised persons

Randomized trials

Available data are currently insufficient to assess safety in severely immunocompromised persons.

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 ].

Non-comparative studies

COVAC-IC is an ongoing prospective observational study (registered with the number NCT04805216 [University Hospitals of North Midlands NHS Trust, 2021 ]) sponsored by University Hospitals of North Midlands NHS Trust that is being conducted in the United Kingdom. It was first registered in March 18, 2021 and plans to enroll 80 immunosuppressed participants with hematological conditions that will receive several COVID-19 vaccines including Moderna COVID-19 Vaccine. It is expected to run until November 15, 2021.

The non-randomized study IROC is currently evaluating the efficacy/safety of the vaccine in cancer patients 18 years of age and older [Indiana University, 2021 ].

The non-randomized study LymphVAX is currently eliciting patient experiences, choices, and side effects associated with the COVID-19 vaccine after breast cancer surgery in women with a history of breast cancer [Massachusetts General Hospital, 2021 ].

The non-randomized study VAX4FRAIL is currently evaluating the efficacy/safety of the vaccine in frail subjects with impaired immuno-competence [Azienda Unità Sanitaria Locale Reggio Emilia, 2021 ].

The non-randomized study CPAT is currently evaluating the efficacy/safety of the vaccine in kidney transplant recipients [National Institute of Allergy and Infectious Diseases (NIAID), 2021 ].

The non-randomized study COVIAAD is currently evaluating the efficacy/safety of the vaccine in patients with rheumatic diseases [McGill University Health Centre/Research Institute of the McGill University Health Centre, 2021 ].

The non-randomized study 000115-C is currently evaluating the efficacy/safety of the vaccine in adults 18 years of age and older with solid tumors or blood cancer [National Cancer Institute (NCI), 2021 ].

The phase 3b, open-label, non-randomized study mRNA-1273-P304 is currently evaluating the efficacy/safety of the vaccine in adult solid organ transplant recipients and healthy controls [ModernaTX, Inc., 2021 ].

The phase 2, non-randomized study VAX-TRES is currently evaluating the efficacy/safety of the vaccine in patient with renal transplants [Maria Joyera Rodríguez, 2021 ].

The non-randomized study Deepak Sahasrabudhe et al is currently evaluating the efficacy/safety of the vaccine in cancer patients 50 to 75 years of age [University of Rochester, 2021 ].

The non-randomized study CVG01 is currently evaluating the efficacy/safety of the vaccine in immune competent subjects and patients with primary or secondary immune deficiency aged 18 years and older [GUVAX (Gothenburg University Vaccine Research Institute), 2021 ].

 

Persons living with HIV

Randomized trials

There were no reported differences in safety among the clinical trial participants with well-controlled HIV. Available data are currently insufficient to evaluate safety for persons living with HIV who are not well controlled on therapy.

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 ].

Safety of the vaccine post-authorization

Post-authorization studies

Comparative studies

Maxime Taquet et al. is a retrospective cohort conducted in United States. The study enrolled 537,913 patients with a confirmed diagnosis of COVID-19. Based on data from ​a federated electronic health records network recording anonymized data from 59 healthcare organizations from January 20, 2020, and March 25, 2021. The authors compared the adverse events between Moderna or Pfizer and Influenza vaccine groups. Results of the study showed that the Moderna/Pfizer group had more cerebral sinus and venous thrombosis (567%, 95% IC 98% to 2134%), and portal vein thrombosis 640% (95% CI 387% to 1024%) than the Influenza group. [Maxime Taquet, 2021 ].


Non-comparative studies
 

Omar M Albalawi et al. was a study conducted in United States. The study enrolled General population that received Pfizer-BioNTech, Moderna, and Janssen Ad26.COV2.S vaccines. Based on data from Vaccine Adverse Event Reporting System (VAERS) between 15 December 2020 to 19 March 2021. Results of the study showed that the Moderna group had more deaths than Pfizer group (7% 95% CI-14% to 33%). [Omar M Albalawi, 2021 ].

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 [Colin Pawlowski, 2021 ].

Pushkar Aggarwal 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 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 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 FDA vaccine Adverse Event Reporting System (VAERS) as of February 12th, 2021. Schulz, J. B et al. was a non-comparative study carried out in Germany, which included 7,126,424 first doses (Pfizer-BioNTech, Moderna, AstraZeneca vaccines) and sought to estimate the incidence of cerebral venous thrombosis (CVT) within a month after administration and the frequency of vaccine-induced immune thrombotic thrombocytopenia (VITT) as an underlying mechanism after vaccination. Given an incidence of 0.22-1.75 per 100,000 person-years for CVT in the general population, these findings point towards a higher risk for CVT after ChAdOx1 vaccination, especially for women [Schulz, J. B., 2021 ].

David Presby et al. is a retrospective cohort conducted in 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 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 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 ].

Desai AP et al. (CDC report) was a safety monitoring non-comparative study that enrolled 3,203 participants that received Moderna COVID-19 vaccine. Results showed that there were 39 (1.22% [95% CI: 0.83%–1.61%]) reported cases of anaphylaxis in the study [Desai AP, 2021 ].

Maria Abbattista 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 Tozinameran, 5.63 (95% CI, 4, 74-6.64) for CX-024414, 21.60 (95% CI, 20.16-23.11)) for CHADOX1 NCOV-19 and 11.48 (95% CI, 9.57-13, 67) for AD26.COV2.S. 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 ].

ACP et al. was a retrospective cohort study conducted in the United Kingdom. The study recruited 373 participants who received the Pfizer-BioNTech, Moderna, and AstraZeneca vaccines. Based on data from the London Cancer Center from December 8, 2020 to February 28, 2021. Of the patients, 88.5% were receiving cancer treatment (36.2% parenteral chemotherapy and 15.3% immunotherapy), 76.1% developed some degree of vaccine-related adverse events (VRAE's) of which 2.1% were grade 3. No grades 4/5 or anaphylaxis were observed. The most common VRAE within 7 days after vaccination were arm pain (61.7%), fatigue (18.2%), and headaches (12.1%). The most common grade 3 VRAE's was fatigue (1.1%). Our results demonstrate that COVID-19 vaccines in cancer patients have mild reactogenicity [So ACP, 2021 ].

Monitoring

WHO recommends the following research and post-authorization monitoring activities:

Safety surveillance and monitoring
- Serious adverse events, anaphylaxis and other serious allergic reactions, Bell’s palsy, cases of multisystem inflammatory syndrome following vaccination, cases of COVID-19 following vaccination that result in hospitalization or death.

Vaccine effectiveness
− Vaccine effectiveness over time and whether protection can be prolonged by booster doses.
− Studies to investigate whether this vaccine reduces SARS-CoV-2 transmission and viral shedding.
− Assessment and reporting of vaccination failures and virus sequence information.

Subgroups
− Prospective studies on the safety of COVID-19 vaccine in pregnant and lactating females.
− Randomized controlled trials on efficacy and safety of vaccination in children below the age of 18 years.
− Safety data on vaccination in immunocompromised people, including patients living with HIV and autoimmune disease.

Vaccination logistics
− Immunogenicity and safety studies of co-administration with other vaccines, including influenza and pneumococcal vaccines, to adults and older persons.
− Safety, immunogenicity, and impact of a delayed second dose, as currently implemented by certain countries.
− Stability of the vaccine under alternative cold-chain distribution and storage conditions.
− Effectiveness of the proposed strategies for the prevention and management of anaphylactic reactions.
− Interchangeability studies within and across COVID-19 vaccine platforms.

References

[WHO, 2021] WHO. WHO Recommendation COVID-19 mRNA Vaccine (nucleoside modified). WHO RECOMMENDATION COVID-19 MRNA VACCINE (NUCLEOSIDE MODIFIED). 2021; WHO. WHO Recommendation COVID-19 mRNA Vaccine (nucleoside modified). WHO RECOMMENDATION COVID-19 MRNA VACCINE (NUCLEOSIDE MODIFIED). 2021;
[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, 2021] WHO. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19. 15 June 2021. 2021; WHO. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19. 15 June 2021. 2021;
[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;
[MINISTERIO DE SALUD DE ARGENTINA, 2021] MINISTERIO DE SALUD DE ARGENTINA. Resolución 2711/2021 RESOL-2021-2711-APN-MS. 2021;
[Health Canada, 2020] Health Canada. Health Canada authorizes Moderna COVID-19 vaccine. 2020; Health Canada. Health Canada authorizes Moderna COVID-19 vaccine. 2020;
[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;
[Moderna, Inc, 2020] Moderna, Inc. Moderna Announces FDA Authorization of Moderna COVID-19 Vaccine in U.S. Press release - Moderna - 18 December 2020. 2020; Moderna, Inc. Moderna Announces FDA Authorization of Moderna COVID-19 Vaccine in U.S. Press release - Moderna - 18 December 2020. 2020;
[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;
[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.
[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.
[FDA, 2021] FDA. FDA NEWS RELEASE. Coronavirus (COVID-19) Update: June 25, 2021. 2021; FDA. FDA NEWS RELEASE. Coronavirus (COVID-19) Update: June 25, 2021. 2021;
[EMA, 2021] EMA. COVID-19 Vaccine Moderna. European Medicines Agency website - product information section. 2021; EMA. COVID-19 Vaccine Moderna. European Medicines Agency website - product information section. 2021;
[World Health Organization, 2021] World Health Organization. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19: interim guidance, 25 January 2021. 2021;
[PAHO, 2020] PAHO. The Immunization Program in the Context of the COVID-19 Pandemic, 26 March 2020. PAHO/FPL/IM/COVID-19/20-0005. 2020; PAHO. The Immunization Program in the Context of the COVID-19 Pandemic, 26 March 2020. PAHO/FPL/IM/COVID-19/20-0005. 2020;
[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.
[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;
[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;
[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
[Canadian Immunization Research Network, 2021] Canadian Immunization Research Network. Mix and Match of the Second COVID-19 Vaccine Dose for Safety and Immunogenicity. clinicaltrials.gov. 2021; Canadian Immunization Research Network. Mix and Match of the Second COVID-19 Vaccine Dose for Safety and Immunogenicity. clinicaltrials.gov. 2021;
[Assistance Publique - Hôpitaux de Paris, 2021] Assistance Publique - Hôpitaux de Paris. Compare Immunological Efficacy of a Vaccine Regimen Combining Two Covid19 mRNA Vaccines (Pfizer-BioNTech and Moderna) With That of a Homologous Vaccination of Each Covid19 mRNA Vaccine. clinicaltrials.gov. 2021; Assistance Publique - Hôpitaux de Paris. Compare Immunological Efficacy of a Vaccine Regimen Combining Two Covid19 mRNA Vaccines (Pfizer-BioNTech and Moderna) With That of a Homologous Vaccination of Each Covid19 mRNA Vaccine. clinicaltrials.gov. 2021;
[International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), 2021] International Network for Strategic Initiatives in Global HIV Trials (INSIGHT). Vaccination for Recovered Inpatients With COVID-19 (VATICO). clinicaltrials.gov. 2021; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT). Vaccination for Recovered Inpatients With COVID-19 (VATICO). clinicaltrials.gov. 2021;
[National Institute of Allergy and Infectious Diseases (NIAID), 2021] National Institute of Allergy and Infectious Diseases (NIAID). A Randomized, Placebo-controlled Crossover Study to Assess the Safety of Administering a Second Dose of a COVID-19 mRNA Vaccine in Individuals Who Experienced a Systemic Allergic Reaction to a National Institute of Allergy and Infectious Diseases (NIAID). A Randomized, Placebo-controlled Crossover Study to Assess the Safety of Administering a Second Dose of a COVID-19 mRNA Vaccine in Individuals Who Experienced a Systemic Allergic Reaction to a
[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
[ModernaTX, Inc., 2021] ModernaTX, Inc.. A Study to Evaluate Safety, Reactogenicity, and Immunogenicity of mRNA-1283 and mRNA-1273 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccines in Healthy Adults Between 18 Years and 55 Years of Age. clinicaltrials.gov. 20 ModernaTX, Inc.. A Study to Evaluate Safety, Reactogenicity, and Immunogenicity of mRNA-1283 and mRNA-1273 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccines in Healthy Adults Between 18 Years and 55 Years of Age. clinicaltrials.gov. 20
[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;
[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
[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;
[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;
[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;
[National Institute of Allergy and Infectious Diseases (NIAID), 2021] National Institute of Allergy and Infectious Diseases (NIAID). A Study of SARS CoV-2 Infection and Potential Transmission in University Students Immunized With Moderna COVID-19 Vaccine. clinicaltrials.gov. 2021; National Institute of Allergy and Infectious Diseases (NIAID). A Study of SARS CoV-2 Infection and Potential Transmission in University Students Immunized With Moderna COVID-19 Vaccine. clinicaltrials.gov. 2021;
[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;
[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;
[Takeda, 2021] Takeda. A Placebo-Controlled Study of TAK-919 in Healthy Japanese Adults (COVID-19). clinicaltrials.gov. 2021; Takeda. A Placebo-Controlled Study of TAK-919 in Healthy Japanese Adults (COVID-19). clinicaltrials.gov. 2021;
[University of Antwerp, 2021] University of Antwerp. Assessment of the immunogenicity and safety of marketed vaccines for COVID-19 after regular schedule and adapted vaccine schedules and routes: BNT162b2 (Comirnaty®; Pfizer-BioNTech), mRNA-1273 Vaccine (COVID-19 Vaccine Moderna®; Mod University of Antwerp. Assessment of the immunogenicity and safety of marketed vaccines for COVID-19 after regular schedule and adapted vaccine schedules and routes: BNT162b2 (Comirnaty®; Pfizer-BioNTech), mRNA-1273 Vaccine (COVID-19 Vaccine Moderna®; Mod
[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;
[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.
[Serre-Yu Wong, 2021] Serre-Yu Wong, Rebekah Dixon, Vicky Martinez Pazos et al. Serological response to COVID-19 vaccination in IBD patients receiving biologics. medRxiv. 2021; Serre-Yu Wong, Rebekah Dixon, Vicky Martinez Pazos et al. Serological response to COVID-19 vaccination in IBD patients receiving biologics. medRxiv. 2021;
[Azienda Socio Sanitaria Territoriale di Cremona, 2021] Azienda Socio Sanitaria Territoriale di Cremona. Effectiveness of mRNA Covid-19 Vaccines on Cancer Patients:Observational Study. (ANTICOV). clinicaltrials.gov. 2021; Azienda Socio Sanitaria Territoriale di Cremona. Effectiveness of mRNA Covid-19 Vaccines on Cancer Patients:Observational Study. (ANTICOV). clinicaltrials.gov. 2021;
[LifeBridge Health, 2021] LifeBridge Health. Quantification of Binding and Neutralizing Antibody Levels in COVID-19 Vaccinated Health Care Workers Over 1 Year. clinicaltrials.gov. 2021; LifeBridge Health. Quantification of Binding and Neutralizing Antibody Levels in COVID-19 Vaccinated Health Care Workers Over 1 Year. clinicaltrials.gov. 2021;
[Dr. Sidney J. Stohs, 2021] Dr. Sidney J. Stohs. Change in Antibody Levels Following SARS-CoV-2 (Covid-19) Vaccinations. clinicaltrials.gov. 2021; Dr. Sidney J. Stohs. Change in Antibody Levels Following SARS-CoV-2 (Covid-19) Vaccinations. clinicaltrials.gov. 2021;
[Clalit Health Services, 2020] Clalit Health Services. Covid-19 Vaccine Effectiveness in Healthcare Personnel in Clalit Health Services in Israel (CoVEHPI). clinicaltrials.gov. 2020; Clalit Health Services. Covid-19 Vaccine Effectiveness in Healthcare Personnel in Clalit Health Services in Israel (CoVEHPI). clinicaltrials.gov. 2020;
[National Institute on Aging (NIA), 2021] National Institute on Aging (NIA). A Clinical Observational Study of SARS-CoV-2 Specific CD8 T-Cell Responses to COVID-19 Vaccines in Humans. clinicaltrials.gov. 2021; National Institute on Aging (NIA). A Clinical Observational Study of SARS-CoV-2 Specific CD8 T-Cell Responses to COVID-19 Vaccines in Humans. clinicaltrials.gov. 2021;
[Lenanrt Friis-Hansen, 2021] Lenanrt Friis-Hansen. Mucosal Immunity in Terms of SARS-CoV-2 Antibodies in Saliva After COVID-19 Infection and Vaccination. clinicaltrials.gov. 2021; Lenanrt Friis-Hansen. Mucosal Immunity in Terms of SARS-CoV-2 Antibodies in Saliva After COVID-19 Infection and Vaccination. clinicaltrials.gov. 2021;
[National Institute of Allergy and Infectious Diseases (NIAID), 2021] National Institute of Allergy and Infectious Diseases (NIAID). Efficacy Study of Phase 1/2 Randomized Interventional Study of SARS-COV-2-Vaccine Candidates Utilizing EUA Dosing. clinicaltrials.gov. 2021; National Institute of Allergy and Infectious Diseases (NIAID). Efficacy Study of Phase 1/2 Randomized Interventional Study of SARS-COV-2-Vaccine Candidates Utilizing EUA Dosing. clinicaltrials.gov. 2021;
[Indiana University, 2021] Indiana University. Immune Responses in Oncology Patients to Novel Coronavirus Vaccines (IROC). clinicaltrials.gov. 2021; Indiana University. Immune Responses in Oncology Patients to Novel Coronavirus Vaccines (IROC). clinicaltrials.gov. 2021;
[Massachusetts General Hospital, 2021] Massachusetts General Hospital. Patient Experiences With the COVID-19 Vaccination After Breast Cancer Treatment. clinicaltrials.gov. 2021; Massachusetts General Hospital. Patient Experiences With the COVID-19 Vaccination After Breast Cancer Treatment. clinicaltrials.gov. 2021;
[NYU Langone Health, 2021] NYU Langone Health. Covid19 Multiple Sclerosis Vaccine Biospecimen Study. clinicaltrials.gov. 2021; NYU Langone Health. Covid19 Multiple Sclerosis Vaccine Biospecimen Study. clinicaltrials.gov. 2021;
[William Beaumont Hospitals, 2021] William Beaumont Hospitals. The Impact of Vaccination on Severity of Illness in COVID-19: A Multicenter Cohort Study. clinicaltrials.gov. 2021; William Beaumont Hospitals. The Impact of Vaccination on Severity of Illness in COVID-19: A Multicenter Cohort Study. clinicaltrials.gov. 2021;
[Azienda Unità Sanitaria Locale Reggio Emilia, 2021] Azienda Unità Sanitaria Locale Reggio Emilia. National Project on Vaccines, COVID-19 and Frail Patients. clinicaltrials.gov. 2021; Azienda Unità Sanitaria Locale Reggio Emilia. National Project on Vaccines, COVID-19 and Frail Patients. clinicaltrials.gov. 2021;
[ModernaTX, Inc., 2021] ModernaTX, Inc.. Post-Marketing Safety Study of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA-1273 COVID-19 Vaccine in the United States. clinicaltrials.gov. 2021; ModernaTX, Inc.. Post-Marketing Safety Study of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA-1273 COVID-19 Vaccine in the United States. clinicaltrials.gov. 2021;
[National Institute of Allergy and Infectious Diseases (NIAID), 2021] National Institute of Allergy and Infectious Diseases (NIAID). COVID Protection After Transplant Pilot Study. clinicaltrials.gov. 2021; National Institute of Allergy and Infectious Diseases (NIAID). COVID Protection After Transplant Pilot Study. clinicaltrials.gov. 2021;
[St. Barnabas Medical Center, 2021] St. Barnabas Medical Center. Effect of Disease Modifying Therapy on Antibody Response to COVID19 Vaccination in Multiple Sclerosis. clinicaltrials.gov. 2021; St. Barnabas Medical Center. Effect of Disease Modifying Therapy on Antibody Response to COVID19 Vaccination in Multiple Sclerosis. clinicaltrials.gov. 2021;
[McGill University Health Centre/Research Institute of the McGill University Health Centre, 2021] McGill University Health Centre/Research Institute of the McGill University Health Centre. COVID-19 Vaccine in Immunosuppressed Adults With Autoimmune Diseases. clinicaltrials.gov. 2021; McGill University Health Centre/Research Institute of the McGill University Health Centre. COVID-19 Vaccine in Immunosuppressed Adults With Autoimmune Diseases. clinicaltrials.gov. 2021;
[National Cancer Institute (NCI), 2021] National Cancer Institute (NCI). A Trial of the Safety and Immunogenicity of the COVID-19 Vaccine (mRNA-1273) in Participants With Hematologic Malignancies and Various Regimens of Immunosuppression, and in Participants With Solid Tumors on PD1/PDL1 Inhibi National Cancer Institute (NCI). A Trial of the Safety and Immunogenicity of the COVID-19 Vaccine (mRNA-1273) in Participants With Hematologic Malignancies and Various Regimens of Immunosuppression, and in Participants With Solid Tumors on PD1/PDL1 Inhibi
[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;
[ModernaTX, Inc., 2021] ModernaTX, Inc.. A Study to Evaluate Safety and Immunogenicity of mRNA-1273 Vaccine in Adult Organ Transplant Recipients and in Healthy Adult Participants. clinicaltrials.gov. 2021; ModernaTX, Inc.. A Study to Evaluate Safety and Immunogenicity of mRNA-1273 Vaccine in Adult Organ Transplant Recipients and in Healthy Adult Participants. clinicaltrials.gov. 2021;
[Diakonessenhuis, 2021] Diakonessenhuis. SARS-CoV-2 immune response. EU Clinical Trials Register. 2021; Diakonessenhuis. SARS-CoV-2 immune response. EU Clinical Trials Register. 2021;
[Regeneron Pharmaceuticals, 2021] Regeneron Pharmaceuticals. COVID-19 Study to Assess Immunogenicity, Safety, and Tolerability of Moderna mRNA-1273 Vaccine Administered With Casirivimab+Imdevimab in Healthy Adult Volunteers. clinicaltrials.gov. 2021; Regeneron Pharmaceuticals. COVID-19 Study to Assess Immunogenicity, Safety, and Tolerability of Moderna mRNA-1273 Vaccine Administered With Casirivimab+Imdevimab in Healthy Adult Volunteers. clinicaltrials.gov. 2021;
[Assistance Publique - Hôpitaux de Paris, 2021] Assistance Publique - Hôpitaux de Paris. Immunogenecity and Safety of VaccinemRNA-1273 in Elderly Volunteers (Over 65 y) Compared to Younger Ones (18-45y). clinicaltrials.gov. 2021; Assistance Publique - Hôpitaux de Paris. Immunogenecity and Safety of VaccinemRNA-1273 in Elderly Volunteers (Over 65 y) Compared to Younger Ones (18-45y). clinicaltrials.gov. 2021;
[Takeda, 2021] Takeda. Survey of the Moderna COVID-19 Vaccine in People at High-Risk of Developing Severe COVID-19 Symptoms. clinicaltrials.gov. 2021; Takeda. Survey of the Moderna COVID-19 Vaccine in People at High-Risk of Developing Severe COVID-19 Symptoms. clinicaltrials.gov. 2021;
[University Hospital, Strasbourg, France, 2021] University Hospital, Strasbourg, France. Monitoring of COVID-19 Vaccine Response in Organ Transplant Patients. clinicaltrials.gov. 2021; University Hospital, Strasbourg, France. Monitoring of COVID-19 Vaccine Response in Organ Transplant Patients. clinicaltrials.gov. 2021;
[Maria Joyera Rodríguez, 2021] Maria Joyera Rodríguez. Study About the Response to the Administration of a Third Dose of mRNA-1273 Vaccine (COVID-19 Vaccine Moderna) in Renal Transplants With Immunological Failure Initial to Vaccination. clinicaltrials.gov. 2021; Maria Joyera Rodríguez. Study About the Response to the Administration of a Third Dose of mRNA-1273 Vaccine (COVID-19 Vaccine Moderna) in Renal Transplants With Immunological Failure Initial to Vaccination. clinicaltrials.gov. 2021;
[University of Rochester, 2021] University of Rochester. Serologic Response to the SARS-CoV-2 mRNA-1273 Vaccine in Select Subsets of Oncology Patients. clinicaltrials.gov. 2021; University of Rochester. Serologic Response to the SARS-CoV-2 mRNA-1273 Vaccine in Select Subsets of Oncology Patients. clinicaltrials.gov. 2021;
[Takeda, 2021] Takeda. Long-Term Follow-up Survey of COVID-19 Vaccine After Vaccination. clinicaltrials.gov. 2021; Takeda. Long-Term Follow-up Survey of COVID-19 Vaccine After Vaccination. clinicaltrials.gov. 2021;
[ModernaTX, Inc., 2021] ModernaTX, Inc.. Moderna COVID-19 Vaccine mRNA-1273 Observational Pregnancy Outcome Study. clinicaltrials.gov. 2021; ModernaTX, Inc.. Moderna COVID-19 Vaccine mRNA-1273 Observational Pregnancy Outcome Study. clinicaltrials.gov. 2021;
[GUVAX (Gothenburg University Vaccine Research Institute), 2021] GUVAX (Gothenburg University Vaccine Research Institute). Immune response to SARS-CoV-2 in health care workers, previously infected subjects, and immunocompromised subjects, before and after Covid-19 vaccination: a phase IV trial. EU Clinical Trials Regis GUVAX (Gothenburg University Vaccine Research Institute). Immune response to SARS-CoV-2 in health care workers, previously infected subjects, and immunocompromised subjects, before and after Covid-19 vaccination: a phase IV trial. EU Clinical Trials Regis
[National Institute of Allergy and Infectious Diseases (NIAID), 2021] National Institute of Allergy and Infectious Diseases (NIAID). SARS Vaccination Reactions. clinicaltrials.gov. 2021; National Institute of Allergy and Infectious Diseases (NIAID). SARS Vaccination Reactions. clinicaltrials.gov. 2021;
[University Hospitals of North Midlands NHS Trust, 2021] University Hospitals of North Midlands NHS Trust. Covid-19 Vaccine Response in Immunocompromised Haematology Patients. clinicaltrials.gov. 2021; University Hospitals of North Midlands NHS Trust. Covid-19 Vaccine Response in Immunocompromised Haematology Patients. clinicaltrials.gov. 2021;
[Petsch B, 2012] Petsch B, Schnee M, Vogel AB et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nature biotechnology. 2012;30(12):1210-6. Petsch B, Schnee M, Vogel AB et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nature biotechnology. 2012;30(12):1210-6.
[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.
[Wang Z, 2021] Wang Z, Schmidt F, Weisblum Y et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature. 2021; Wang Z, Schmidt F, Weisblum Y et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature. 2021;
[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.
[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;
[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.
[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.
[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;
[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;
[Popkin BM, 2020] Popkin BM, Du S, Green WD, Beck MA et al. Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2020;2 Popkin BM, Du S, Green WD, Beck MA et al. Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2020;2
[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-
[Alisa Fox, 2021] Alisa Fox, Claire DeCarlo, Xiaoqi Yang et al. Comparative profiles of SARS-CoV-2 Spike-specific milk antibodies elicited by COVID-19 vaccines currently authorized in the USA. medRxiv. 2021; Alisa Fox, Claire DeCarlo, Xiaoqi Yang et al. Comparative profiles of SARS-CoV-2 Spike-specific milk antibodies elicited by COVID-19 vaccines currently authorized in the USA. medRxiv. 2021;
[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.
[Thompson MG, 2021] Thompson MG, Burgess JL, Naleway AL et al. Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines. The New England journal of medicine. 2021; Thompson MG, Burgess JL, Naleway AL et al. Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines. The New England journal of medicine. 2021;
[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).
[Khan N, 2021] Khan N, Mahmud N. Effectiveness of SARS-CoV-2 vaccination in a Veterans Affairs Cohort of Inflammatory Bowel Disease Patients with Diverse Exposure to Immunosuppressive Medications. Gastroenterology. 2021; Khan N, Mahmud N. Effectiveness of SARS-CoV-2 vaccination in a Veterans Affairs Cohort of Inflammatory Bowel Disease Patients with Diverse Exposure to Immunosuppressive Medications. Gastroenterology. 2021;
[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;
[Kristin Andrejko, 2021] Kristin Andrejko, Jake M Pry, Jennifer F Myers et al. Prevention of COVID-19 by mRNA-based vaccines within the general population of California. medRxiv. 2021; Kristin Andrejko, Jake M Pry, Jennifer F Myers et al. Prevention of COVID-19 by mRNA-based vaccines within the general population of California. medRxiv. 2021;
[Pilishvili T, 2021] Pilishvili T, Gierke R, Fleming-Dutra KE et al. Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel. The New England journal of medicine. 2021; Pilishvili T, Gierke R, Fleming-Dutra KE et al. Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel. The New England journal of medicine. 2021;
[Shen X, 2021] Shen X, Tang H, McDanal C et al. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines. Cell host & microbe. 2021;29(4):529-539.e3. Shen X, Tang H, McDanal C et al. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines. Cell host & microbe. 2021;29(4):529-539.e3.
[Wang, P., 2021] Wang, P., Nair, M. S., Liu, L. et al. Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7. bioRxiv. 2021; Wang, P., Nair, M. S., Liu, L. et al. Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7. bioRxiv. 2021;
[Venkata Viswanadh Edara, 2021] Venkata Viswanadh Edara, Katharine Floyd, Lilin Lai et al. Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant. medRxiv. 2021; Venkata Viswanadh Edara, Katharine Floyd, Lilin Lai et al. Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant. medRxiv. 2021;
[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;
[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;
[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
[Tsui NB, 2002] Tsui NB, Ng EK, Lo YM. Stability of endogenous and added RNA in blood specimens, serum, and plasma. Clinical chemistry. 2002;48(10):1647-53. Tsui NB, Ng EK, Lo YM. Stability of endogenous and added RNA in blood specimens, serum, and plasma. Clinical chemistry. 2002;48(10):1647-53.
[ Kauffman KJ, 2016] Kauffman KJ, Webber MJ, Anderson DG. Materials for non-viral intracellular delivery of messenger RNA therapeutics. Journal of controlled release : official journal of the Controlled Release Society. 2016;240:227-234. Kauffman KJ, Webber MJ, Anderson DG. Materials for non-viral intracellular delivery of messenger RNA therapeutics. Journal of controlled release : official journal of the Controlled Release Society. 2016;240:227-234.
[Guan S, 2017] Guan S, Rosenecker J. Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems. Gene therapy. 2017;24(3):133-143. Guan S, Rosenecker J. Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems. Gene therapy. 2017;24(3):133-143.
[Thess A, 2015] Thess A, Grund S, Mui BL et al. Sequence-engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large Animals. Molecular therapy : the journal of the American Society of Gene Therapy. 2015;23(9):1456-64. Thess A, Grund S, Mui BL et al. Sequence-engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large Animals. Molecular therapy : the journal of the American Society of Gene Therapy. 2015;23(9):1456-64.
[Karikó K, 2011] Karikó K, Muramatsu H, Ludwig J et al. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucleic acids research. 2011;39(21):e142. Karikó K, Muramatsu H, Ludwig J et al. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucleic acids research. 2011;39(21):e142.
[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.
[Maxime Taquet, 2021] Maxime Taquet, Masud Husain, John R Geddes et al. Cerebral venous thrombosis and portal vein thrombosis: a retrospective cohort study of 537,913 COVID-19 cases. medRxiv. 2021; Maxime Taquet, Masud Husain, John R Geddes et al. Cerebral venous thrombosis and portal vein thrombosis: a retrospective cohort study of 537,913 COVID-19 cases. medRxiv. 2021;
[Omar M Albalawi, 2021] Omar M Albalawi, Maha I Alomran, Ghada M Alsagri et al. Analyzing the U.S. Post-marketing safety surveillance of COVID-19 vaccines. medRxiv. 2021; Omar M Albalawi, Maha I Alomran, Ghada M Alsagri et al. Analyzing the U.S. Post-marketing safety surveillance of COVID-19 vaccines. medRxiv. 2021;
[Colin Pawlowski, 2021] Colin Pawlowski, John Rincon-Hekking, Samir Awasthi et al. Cerebral venous sinus thrombosis (CVST) is not significantly linked to COVID-19 vaccines or non-COVID vaccines in a large multi-state US health system. medRxiv. 2021; Colin Pawlowski, John Rincon-Hekking, Samir Awasthi et al. Cerebral venous sinus thrombosis (CVST) is not significantly linked to COVID-19 vaccines or non-COVID vaccines in a large multi-state US health system. medRxiv. 2021;
[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;
[Schulz, J. B., 2021] Schulz, J. B., Berlit, P., Diener, H.-C. et al. COVID-19 vaccine-associated cerebral venous thrombosis in Germany. medRxiv. 2021; Schulz, J. B., Berlit, P., Diener, H.-C. et al. COVID-19 vaccine-associated cerebral venous thrombosis in Germany. medRxiv. 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.
[Desai AP, 2021] Desai AP, Desai AP, Loomis GJ. Relationship between pre-existing allergies and anaphylactic reactions post mRNA COVID-19 vaccine administration. Vaccine. 2021; Desai AP, Desai AP, Loomis GJ. Relationship between pre-existing allergies and anaphylactic reactions post mRNA COVID-19 vaccine administration. Vaccine. 2021;
[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;
[So ACP, 2021] So ACP, McGrath H, Ting J et al. COVID-19 Vaccine Safety in Cancer Patients: A Single Centre Experience. Cancers. 2021;13(14). So ACP, McGrath H, Ting J et al. COVID-19 Vaccine Safety in Cancer Patients: A Single Centre Experience. Cancers. 2021;13(14).
Back to dashboard