Sinopharm/BIBP COVID-19 vaccine

Extended version of the vaccine

Sinopharm/BIBP COVID-19 vaccine

Authorization

World Health Organization Emergency Use Listing Procedure
Listed for emergency use
Status of assessment: finalized May 7, 2021 [WHO, 2021 ]

European Commission (based upon the recommendation of the European Medicines Agency)
Not authorized.

China's National Medical Products Administration
Authorized [National Medical Products Administration of China, 2020 ].
31 December 2020
Conditional Marketing Authorization in individuals 18 years of age and older.

Regulatory Authorities of Regional Reference in the Americas

National Administration of Drugs, Foods and Medical Devices (ANMAT, Argentina)
Authorized for emergency use: 21 February, 2021 [Fundación Femeba, 2021 ]

Brazilian Health Regulatory Agency (ANVISA, Brazil)
Not authorized

Health Canada
Not authorized

Public Health Institute (ISP, Chile)
Not authorized

National Institute of Food and Drug Monitoring (INVIMA, Colombia)
Not authorized

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

U.S. Food and Drug Administration
Not authorized

Federal Commission for the Protection against Sanitary Risk (COFEPRIS, Mexico)
Not authorized

Authorization in other jurisdictions in the Americas
Bolivia
Guyana
Peru
Venezuela

Authorization in other jurisdictions
Bahrain
Bangladesh
Belarus
Brunei Darussalam
Cambodia
Cameroon
Comoros
Egypt
Gabon
Iran
Iraq
Jordan
Kyrgyzstan
Laos
Lebanon
Maldives
Mongolia
Montenegro
Morocco
Mozambique
Namibia
Nepal
Niger
North Macedonia
Pakistan
Republic of the Congo
Senegal
Serbia
Seychelles
Sierra Leone
Somalia
United Arab Emirates
Zimbabwe

Manufacturing

Manufacturer
Beijing Institute of Biological Products Co. Ltd.; China. Manufacturer of the inactivated vaccine against COVID-19.
Other manufacturers
G42 Healthcare; Dubai, United Arab Emirates. Production and filling of Sinopharm/BIBP COVID-19 vaccine in the UAE. The vaccine will be called Hayat-Vax when manufactured in the UAE, but is the same inactivated vaccine from the Beijing Institute of Biological Product (BiBP) [Arabian Business, 2021 ].

General characteristics

Sinopharm/BIBP COVID-19 vaccine is an inactivated vaccine that consists of virus particles that have been grown in culture and then were inactivated to lose disease-producing capacity, while still stimulating an immune response. Three SARS-CoV-2 strains were isolated from the bronchoalveolar lavage samples or throat swabs of hospitalized patients from a COVID-19 outbreak to develop preclinical in vitro neutralization and challenge models for an inactivated SARS-CoV-2 vaccine candidate. The three strains were 19nCoV-CDC-Tan-HB02 (HB02), 19nCoV-CDC-Tan-Strain03 (CQ01) and 19nCoV-CDC-Tan-Strain04 (QD01) [Wang H., 2020 ].

HBO2 strain showed optimal replication and generated the highest virus yields in Vero cells among the three viral strains. Therefore the HB02 strain was selected for the development of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV) [Wang H., 2020 ].

Dosage form and ingredients
The pharmaceutical form is a suspension for intramuscular injection that is provided in a monodose vial of 0.5 ml.

The vaccine contains the following ingredients:
Active ingredient:
6.5 U of inactivated SARS-CoV-2 antigen
Adjuvant:
0.225 mg of aluminum hydroxide
Excipients:
1.4 mg disodium hydrogen phosphate
0.1373 mg sodium dihydrogen phosphate
4.25 mg sodium chloride

Risk considerations

Inactivated vaccines have been successfully employed for more than 60 years. These vaccines are made from highly purified viruses that have been made noninfectious. Such vaccines have been found to be safe and effective for the prevention of diseases caused by viruses like influenza and poliovirus [Gao Q, 2020 ]. Inactivated vaccines require the use of adjuvants which may cause undesirable reactions in vaccinated individuals [Wang H., 2020 ].

Previous experiences with the development of vaccine candidates against SARS-CoV and MERS-CoV had raised concerns about pulmonary immunopathology, probably caused by a response from type 2 (Th2) helper T cells. Although the cellular response can be elicited by many vaccines, protection against subsequent coronavirus infections is largely mediated for humoral immunity. The 'cytokine storm' induced by excess T cells has been shown to accentuate the pathogenesis of COVID-19 [Qiang Gao, 2020 ].

Dosification and schedule

Dose-finding studies
[Xia, Shengli, 2021 ] was a dose-finding, randomized, phase 1/2 trial sponsored by Sinopharm. It was registered with the trial registry number ChiCTR2000032459.
The trial included healthy participants ≥18 years.
The sample size was 192 (6 cohorts of 32). The mean age of the participants was 53.7 in the whole study. Participants were 47% male, 53% female; 50% aged 18-59 years, 50% aged ≥60 years.
Participants were randomly assigned in a 3:1 ratio to receive Sinopharm COVID-19 vaccine (2µg, 4µg or 8µg) or placebo.
For vaccine recipients in the group aged 18-59 years, 19 (79%) of 24 in the 2 µg group, 21 (87%) of 24 in the 4 µg group, and 23 (96%) of 24 in the 8 µg group seroconverted by day 14. Seroconversion rates reached 100% in all three cohorts on day 28. For vaccine recipients in the group aged 60 years and older, eight (4%) of 23 in the 2 µg group and 11 (46%) of 24 in each of the 4 µg and 8 µg groups seroconverted by day 14. 21 (91%) of 23 in the 2 µg group, 22 (92%) of 24 in the 4 µg group, and 22 (96%) of 23 in the 8 µg group seroconverted by day 28. The neutralizing antibodies in all placebo recipients were negative throughout the trials [Xia, Shengli, 2021 ].

There is no data available on the interchangeability of the Sinopharm/BIBP COVID-19 vaccine with other COVID-19 vaccines to complete the vaccination series.
There is no evidence yet about the effects of the coadministration of Sinopharm/BIBP COVID-19 vaccine with other vaccines included in routine vaccination programs

Indications and contraindications

Indications
Sinopharm/BIBP COVID-19 vaccine is indicated in adult individuals from 18 years to 59 year old (inclusive) [Ministerio de Salud Argentina, 2021 ].

Contraindications
The vaccine is contraindicated in individuals with a known history of a severe allergic reaction to any component of the vaccine.
The second dose of the vaccine should NOT BE GIVEN to those who have experienced anaphylaxis to the first dose.
Exacerbation of chronic diseases, which imply compromise of the general state [Ministerio de Salud Argentina, 2021 ]
The vaccine is contraindicated in individuals with a known history of a severe allergic reaction to any component of vaccines [Ministerio de Salud Argentina, 2021 ].
Uncontrolled epilepsy or other progressive neurological disorder [Ministerio de Salud Argentina, 2021 ]

Precautions
Severe allergic reaction (e.g. anaphylaxis) to a previous dose of any vaccine (not including Sinopharm/BIBP COVID-19 vaccine).
In general, persons with an immediate non-anaphylactic allergic reaction to the first dose should not receive additional doses, unless recommended after review by a health professional with specialist expertise.
As a small number of anaphylactic reactions have also been reported in vaccines without a history of anaphylaxis, it is recommended that Sinopharm/BIBP COVID-19 vaccine should be administered only in settings where anaphylaxis can be treated.
Severe allergic reaction (e.g. anaphylaxis) to an injectable medication.
Vaccination should be postponed in individuals suffering from acute severe febrile illness, or acute infection [Ministerio de Salud de Perú, 2021 ].
Reactions related to stress or anxiety, such as syncope or hyperventilation may occur in association with vaccination as a psychogenic response to the needle injection. It is important that precautions are in place to avoid injury from fainting.
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 [Ministerio de Salud de Perú, 2021 ].
The available data on Sinopharm/BIBP COVID-19 vaccine on pregnant females are insufficient to assess vaccine efficacy in pregnancy since no clinical trial evaluating vaccines to prevent COVID-19 has included pregnant females. The vaccine should only be given to pregnant females if the risks outweigh the benefit.
The available data on Sinopharm/BIBP COVID-19 vaccine on lactating females are insufficient to assess whether the vaccine is excreted in human milk or if there is any associated risk.
The available data on Sinopharm/BIBP COVID-19 vaccine on children are insufficient to assess vaccine efficacy since no clinical trial evaluating vaccines to prevent COVID-19 has included children.
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.
Vaccination may be offered regardless of a person‘s history of symptomatic or asymptomatic SARS-CoV-2 infection.
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.

Storage and logistics

Storage
Sinopharm/BIBP COVID-19 vaccine is provided as a suspension stored at 5°C /41°F (between 2°C to 8°C [35° to 46°F]).
Unopened vaccine vials can be stored refrigerated between 2°C to 8°C [35° to 46°F] for up to 24 months [Ministerio de Salud Argentina, 2021 ].
Do not apply dry ice to the package or the vials as a method of refrigeration

Protect the vials from light.
Do not freeze

Logistic at the time of administration
Inspect the vial before use. SINOPHARM vaccine is an opalescent, injectable suspension with possible precipitate formation that must be resuspended by inverting the vial several times to mix [Ministerio de Salud Argentina, 2021 ].
The vial should be discarded if particles or differences are observed in the described appearance of the vaccine.
The single-dose vial should be used immediately after opening.
Do not shake the vial roughly.
To improve traceability, the name and batch number of the administered product should be clearly recorded.

Administration
1.Using aseptic technique, clean the vial stopper with a single-use antiseptic swab.
2. Use a 3 ml reuse prevention syringe (RUP) or a 5 ml RUP syringe, and a 21G or narrower needle.
3. Gently invert the vial to mix, and withdraw the 0.5 ml dose. If the amount of vaccine remaining in the vial cannot provide a full 0.5 ml dose, discard the vial and the remaining volume.
4. Administer the vaccine intramuscularly, preferably into the deltoid muscle. Do not administer the vaccine intravascularly, subcutaneously, or intradermally.

Due to the high risk that discarded vials of COVID-19 vaccines may be recovered, it is essential that they are guaranteed to be safely disposed of at the site of use; or study the possibility of applying reverse logistics, if the safe treatment and disposal of vaccine residues cannot be guaranteed, so that they are transferred to the place established for that purpose. Otherwise, consider the possibility that the discarded vaccine vials are shredded, if there is a safe way to do so [WHO, 2021 ].

Clinical studies - general characteristics

Randomized trials
Xia S et al [Xia, Shengli, 2021 ] was a dose-escalation, randomized, double-blind, placebo-controlled, phase 1/2 trial sponsored by Center for Disease Control and Prevention, Liangyuan District, Shangqiu City, Henan Province, China and conducted in China. It was registered with clinical trial number ChiCTR2000032459).
The trial included healthy people aged 18-80 years, who were negative for serum-specific IgM/IgG antibodies against SARS-CoV-2.
The sample size was 192. The mean age of the participants was 54 years and the proportion of females was 50%.
Participants were each randomly assigned to receive two doses of 2 µg, 4 µg, or 8 µg of vaccine or placebo in a 3:1 ratio. Therefore, 144 participants received vaccine and 48 participants received placebo.


Ongoing randomized trials
Cov-Peru is an ongoing phase 3 trial (registered with the number NCT04612972 [Universidad Peruana Cayetano Heredia, 2020 ]) sponsored by Universidad Peruana Cayetano Heredia that is being conducted in Perú. It was first registered in November 2020 and plans to enroll 6000 healthy adults ≥ 18 years of age that will receive the inactivated SARS CoV 2 vaccine (Vero cell). It is expected to run until September 2021.

CNBG2020003SQ is an ongoing randomized, phase 3 trial (registered with the number NCT04510207 [China National Biotec Group Company Limited, 2020 ]) sponsored by China National Biotec Group Company Limited that is being conducted in Bahrain, Egypt, Jordan and the United Arab Emirates. It was first registered in August, 2020 and plans to enroll 45000 healthy individuals aged 18 years old and above. It will evaluate the efficacy, safety and immunogenicity of inactivated sars-cov-2 vaccines (vero cell). It is expected to run until September, 2021.

BIBP2020003AR is an ongoing randomized, phase 3 trial (registered with the number NCT04560881 [Laboratorio Elea Phoenix S.A., 2020 ]) sponsored by Laboratorio Elea Phoenix S.A. that is being conducted in Argentina. It was first registered in September, 2020 and plans to enroll 3000 healthy people aged between 18 and 85 years. The objective is to evaluate the efficacy, immunogenicity and safety of the inactivated vaccine. It is expected to run until December, 2021.

Al Kaabi N et al. is an ongoing phase 3 trial (registered with the number ChiCTR2000034780 [China National Biotec Group Co.Ltd , 2020 ]) sponsored by China National Biotec Group Co.Ltd, which is being conducted in China. It was first registered in July, 2020 and plans to enroll 4500 healthy adults ≥ 18 years of age. The objective is to evaluate the protective efficacy of inactivated SARS-CoV-2 Vaccine (Vero Cell) after full course of immunization in preventing diseases caused by the SARS-CoV-2. It is expected to run until July, 2021.

Other ongoing registered studies
NJGLVAC-001 is an ongoing prospective cohort study (registered with the number NCT04729374 [The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, 2021 ]) sponsored by the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, that is being conducted in China. It was first registered in January, 2021 and plans to enroll 200 adults 18 to 59 years of age. The objective is to analyze the vaccine´s immune response. It is expected to run until December, 2023.

AssiutU21 is an ongoing prospective cohort study (registered with the number NCT04706143 [Assiut University, 2021 ]) sponsored by Assiut University, that is being conducted in Egypt. It was first registered in January, 2021 and plans to enroll 100 adults 25 to 65 years of age. It will evaluate the immune responses in adults, up to 8 weeks after vaccination with a single or double dose of different vaccines, including: inactivated (Sinopharm), mRNA (Pfizer/ BioNTech) and viral vector (Oxford/AZ- ChAdOx1 nCoV-19) vaccines. It is expected to run until August, 2021.

Methods used to assess efficacy and effectiveness

Xia S et al trial [Xia, Shengli, 2021 ]
Primary efficacy endpoint
The primary efficacy endpoint was the humoral immunogenicity outcomes measured using an infectious SARS-CoV-2 neutralizing assay and expressed as neutralizing antibody geometric mean titre (GMT).
Seroconversion was defined as an increase in post-vaccination titre of four-fold or more from baseline.

Methods used to assess safety

Xia S et al trial [Xia, Shengli, 2021 ]
Primary safety endpoint
Number of adverse reactions within 7 days after the first and second vaccinations.
Measured by any abnormal change in laboratory at day 4 post-inoculations, and adverse events within 28 days after the first and the second vaccinations across the treatment groups were analyzed as secondary safety endpoints.

Efficacy and effectiveness of the vaccine

Efficacy of the vaccine in preclinical studies

To assess the immunogenicity of the vaccine, BALB / c mice were injected with different vaccine schedules (2, 4 or 8 µg / dose). In the one-dose immunization group, mice were administered intraperitoneally with a high (8 µg / dose), medium (4 µg / dose), or low (2 µg / dose) dose of vaccine on day 0, then, on days 7, 14, 21 and 28 post-inoculation, the levels of neutralizing antibodies were evaluated. The results showed that the seroconversion rate in the high, medium and low dose groups reached 100% at day 7 after immunization, and the effect of immunization was time-dependent [Wang H., 2020 ].
In the two-dose immunization group, two immunization programs were assessed at days 0/7, days 0/14, and days 0/21, respectively. The seropositivity of the high, medium and low-dose groups from all three immunization programs reached 100% at 7 days after the second immunization. The immunogenicity of a three-dose immunization program, in which the mice were intraperitoneally administered a high (8 µg/dose), middle (4 µg/dose), or low (2 µg/dose) dose of vaccine at days 0, 7, and 14, showed that seroconversion rate in all three groups reached 100% at day 7 after the first immunization [Wang H., 2020 ].

Immunogenicity of the vaccine was tested in different animal models: rabbits, guinea pigs, rats, and mice. The animals were immunized with high (8 µg/dose), middle (4 µg/dose), or low (2 µg/dose) doses of vaccine in the different immunization programs. The seroconversion rate reached 100% at 21 days after immunization in all animal models in all the immunization programs tested. [Wang H., 2020 ]
Immunogenicity was also tested in primates. One group of macaques was selected to be immunized twice, on days 0 and 14, while another group received physiological saline intramuscularly to act as control. The experimental groups were injected intramuscularly with a low dose (2 µg / dose) or a high dose (8 µg / dose) of the vaccine. Subsequently, on day 24 (10 days after the second immunization), all macaques were challenged intratracheally with 106 TCID50 of SARS-CoV-2. Body temperature measurements were performed in both the vaccinated and placebo groups. The temperatures of both groups fluctuated within the normal range 7 days after the exposure to the virus. Furthermore, the biochemical parameters after vaccination remained constant. [Wang H., 2020 ]

Efficacy of the vaccine in clinical trials

Main immunogenicity outcomes

Xia et al was a a dose-escalation, randomized trial. The trial included healthy people aged 18-80 years, who were negative for serum-specific IgM/IgG antibodies against SARS-CoV-2. The sample size was 192. The mean age of the participants was 54 years and the proportion of females was 50%.
Participants were randomly assigned to receive placebo or vaccine. In phase 1, on days 0 and 28, the intervention group received Sinopharm/BBIBP COVID-19 vaccine containing 2 µg, 4 µg, or 8 µg total protein, and the control group received placebo.
Neutralizing antibody mean titres were higher at day 42 in the group aged 18-59 years: 87·7 for the 2 µg group; 211·2 for the 4 µg group; and 228·7 for the 8 µg group. In the elderly group of participants (>60 years), mean titres were 80·7 in the 2 µg group; 131·5 in the 4 µg group; and 170·87 in the 8 µg group [Xia, Shengli, 2021 ].

Contracting COVID-19

The risk of contracting any COVID-19 infection has not yet been reported, so it was not possible to estimate the effect for this outcome.


Contracting severe COVID-19

The risk of contracting severe COVID-19 infection has not yet been reported, so it was not possible to estimate the effect for this outcome.




Efficacy and effectiveness of the vaccine on subgroups

Sex

Randomized trials
The proportion of females in the phase 2 of the Xia S et al trial was 54.7% (245 out of 448 participants) [Xia, Shengli, 2021 ].
The proportion of females in the phase 1 of the Xia S et al trial was 53% (102 out of 192 participants) [Xia, Shengli, 2021 ].
Seroconversion rates were consistent in the different sex groups.

Age

Randomized trials
The proportion of participants >60 years of age in the Xia S et al was 50% (96 out of 192 participants) [Xia, Shengli, 2021 ].
For vaccine recipients in the group aged 18-59 years. Seroconversion rates reached 100% in all three cohorts on day 28.
For vaccine recipients in the group aged 60 years and older, 91% in the 2 µg group,92% in the 4 µg group, and 96% in the 8 µg group seroconverted by day 28.
Non-comparative studies
AssiutU21 is an ongoing prospective cohort study (registered with the number NCT04706143 [Assiut University, 2021 ]), that will evaluate the immune responses in adults aged 25 to 65 years, of different vaccines including; inactivated (Sinopharm), m Biontech) and viral vector (Oxford / AZ- ChAdOx1 nCoV-19) vaccines.

Children and adolescents

Randomized trials
Children were excluded from the Xia S et al, so no data are available for this subgroup [Xia, Shengli, 2021 ].
Pregnancy

Randomized trials
Pregnant females were excluded from the Xia S et al, so no data are available for this subgroup [Xia, Shengli, 2021 ].
Breast-feeding

Randomized trials
Breastfeeding females were excluded from the Xia S et al, so no data are available for this subgroup [Xia, Shengli, 2021 ].
Immunocompromised persons

Randomized trials
Immunocompromised participants were excluded from the Xia S et al, so no data are available for this subgroup [Xia, Shengli, 2021 ].

Other data from vaccine efficacy and effectiveness

Duration of protection

Randomized trials
The exact duration of protection provided by the vaccine is unknown, as it is still being determined by ongoing clinical trials.
Other studies
None available
Limitations of vaccine effectiveness

Comparative studies
None available
Non-comparative studies
None available
SARS-CoV-2 variants

Comparative studies
Neutralization activity was assessed in 24 serum samples from participants in two clinical trials, 12 of whom had been vaccinated with Sinopharm/BBIBP COVID-19 vaccine. Neutralizing activity was measured in these serum samples against live SARS-CoV-2 strains GDPCC (501Y.V2). SARS-CoV-2 strains HB02 (wild type) and BJ01 (D614G) were tested as the control.
The serum samples preserved neutralization of the 501Y.V2 variant, with slightly reduced geometric mean titres (GMTs) compared with their titres against the wild type or D614G strains. Findings suggest that the 501Y.V2 variant does not escape the immunity induced by vaccines targeting the whole virus (BBIBP-CorV) [Huang B, 2021 ].

Safety of the vaccine

Safety of the vaccine in preclinical studies

Vaccine was tested in Sprague-Dawley rats to evaluate the acute toxicity of the inactivated vaccine. In this study, 20 rats were divided into two groups and intramuscularly injected with 3 doses (8 µg/dose) of vaccine and physiological saline as the control. After inoculation, all rats were continuously observed for 14 days and euthanized at day 15 to assess systematic anatomy and for general observation. No cases of death or impending death or obvious clinical signs were observed in any of the groups over the 14 days after vaccine inoculation [Wang H., 2020 ].
Systemic anaphylaxis was subsequently evaluated by intramuscular and intravenous injections in guinea pigs. Thirty-six male guinea pigs were divided into 4 groups, 2 control groups and 2 intervention groups. The results showed no abnormal reactions during the inoculation and follow-up period, by clinical observation and measurement of the body weights of the guinea pigs. No allergic reaction symptoms were found in the negative control group or experimental group [Wang H., 2020 ].
The long-term toxicity of the vaccine was further evaluated in cynomolgus monkeys. Forty cynomolgus monkeys were divided into 4 groups and intramuscularly injected with a control solution or 2, 4, or 8 µg of vaccine in a volume of 0.5 ml. No cases of death or significant abnormalities in clinical physiological and pathological indicators were observed. The animals showed only local irritation characterized by mild to severe granulomatous inflammation due to injection, but this reaction was absent at 2 weeks after injection. The no observed adverse effect level was found to be 8 µg/dose in this trial No allergic reaction symptoms were found in the negative control group or experimental group [Wang H., 2020 ].

Safety of the vaccine in clinical trials

Key messages

Sinopharm/BIBP COVID-19 vaccine increases the risk of overall adverse events

Main safety outcomes of Sinopharm/BIBP COVID-19 vaccine

Overall adverse events (30 days after 1st or 2nd dose)

The relative risk of any adverse events in the group that received Sinopharm/BIBP COVID-19 vaccine versus the group that received placebo or no treatment was 1.33 (95% CI 0.85 to 2.1). This means Sinopharm/BIBP COVID-19 vaccine increases the risk of any adverse events in 33%, compared with placebo or no treatment.

Figure - Forest plot of risk ratio meta-analysis. Outcome:Any adverse events. Comparison: Sinopharm/bbibp covid-19 vaccine versus placebo vaccine

In the trial identified in this review, 21 people not receiving Sinopharm/BIBP COVID-19 vaccine out of 112 presented this outcome (188 per 1000) versus 78 out of 336 in the group that did receive it (232 per 1000). In other words, 44 people per 1000 did develop the outcome because of the vaccine.

Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as moderate. We downgraded the certainty of the evidence for imprecision because the confidence interval includes the possibility of no effect.

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.


Serious adverse events

The total number of serious adverse events was not reported as a group, so it was not possible to estimate the effect for this outcome.


Summary of findings table (iSoF)

Safety of the vaccine in subgroups

Sex

Randomized trials
Safety profile of the Sinopharm/BIBP COVID-19 vaccine was not evaluated across sex groups.

Age

Randomized trials
For the vaccine recipients in the group aged 60 years and older (n=72), pain at the injection site was the most frequent adverse reaction (one [4%] in the 2 µg group, four [17%] in the 4 µg group, and four [17%] in the 8 µg group), an additional injection site adverse reaction was induration (two [3%] of 72) [Xia, Shengli, 2021 ].
The most common systemic adverse reactions reported in the >60 age group (n=72) were fever (one [1%]) and fatigue (one [1%]), reported in the 8 µg cohort; and headache (one [1%]), diarrhea (one [1%]), and joint pain (one [1%]) reported in the 4 µg cohort. All adverse reactions were mild or moderate in severity. No serious adverse event was reported within 28 days post vaccination for all cohorts [Xia, Shengli, 2021 ].
Children and adolescents

Randomized trials
Children and adolescents were excluded from the Xia S et al, so no data are available for this subgroup [Xia, Shengli, 2021 ].
Pregnancy

Randomized trials
Pregnant females were excluded from the Xia et al, so no data are available for this subgroup [Xia, Shengli, 2021 ].
Breast-feeding

Randomized trials
Breastfeeding females were excluded from the Xia et al, so no data are available for this subgroup [Xia, Shengli, 2021 ].
Immunocompromised persons

Randomized trials
Immunocompromised participants were excluded from the Xia et al, so no data are available for this subgroup [Xia, Shengli, 2021 ].

Safety of the vaccine post-authorization

Post-authorization studies

Comparative studies
None available
Non-comparative studies
None available
Case reports and case series
None available

Spontaneous report data

Disclaimer: Reporting suspected adverse reactions after authorization of the medicinal product is important because it allows continuous monitoring of the benefit/risk balance of the vaccines. However, they do not indicate a causal association between the vaccine and the observed effects. Furthermore, this information should not be used to estimate the frequency of adverse events in people receiving the vaccine or to make comparisons between different vaccines. The information emerging about possible adverse effects needs to be carefully evaluated in order to first establish if the adverse effect might have been caused by the vaccine.

To date, in Argentina, 127/210 (60.4%) local and systemic mild to moderate adverse events have been reported related to Sinopharm/BIBP vaccine against COVID-19. No serious adverse events related to the vaccine [Ministerio de Salud Argentina, 2021 ] have been reported.

Monitoring

WHO recommends the following research and post-authorization monitoring activities [World Health Organization, 2021 ]:
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 persons, including persons living with HIV and persons with autoimmune disease.
Vaccination logistics
− immunogenicity and safety studies with co-administration of 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 lists additional COVID-19 vaccine for emergency use and issues interim policy recommendations. Press release - World Health Organization - 7 May 2021. 2021; WHO. WHO lists additional COVID-19 vaccine for emergency use and issues interim policy recommendations. Press release - World Health Organization - 7 May 2021. 2021;
[National Medical Products Administration of China, 2020] National Medical Products Administration of China. China grants conditional approval for first COVID vaccine. 2020; National Medical Products Administration of China. China grants conditional approval for first COVID vaccine. 2020;
[Fundación Femeba, 2021] Fundación Femeba. Argentina autoriza la vacuna contra el SARS-CoV-2 de Sinopharm. 2021; Fundación Femeba. Argentina autoriza la vacuna contra el SARS-CoV-2 de Sinopharm. 2021;
[Arabian Business, 2021] Arabian Business. Sinopharm Covid-19 shot dubbed Hayat Vax for local rollout after UAE-China deal. 2021; Arabian Business. Sinopharm Covid-19 shot dubbed Hayat Vax for local rollout after UAE-China deal. 2021;
[Wang H., 2020] Wang H., Zhang Y., Zhao Y. et al. Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2. Cell. 2020;182(3):713-721.e9. Wang H., Zhang Y., Zhao Y. et al. Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2. Cell. 2020;182(3):713-721.e9.
[Gao Q, 2020] Gao Q, Bao L, Mao H et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science (New York, N.Y.). 2020;369(6499):77-81. Gao Q, Bao L, Mao H et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science (New York, N.Y.). 2020;369(6499):77-81.
[Qiang Gao, 2020] Qiang Gao, Linlin Bao, Haiyan Mao et al. Rapid development of an inactivated vaccine for SARS-CoV-2. bioRxiv. 2020; Qiang Gao, Linlin Bao, Haiyan Mao et al. Rapid development of an inactivated vaccine for SARS-CoV-2. bioRxiv. 2020;
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