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 ].

Efficacy of preclinical studies on the vaccine

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 ].

Key messages

Sinopharm/BIBP COVID-19 vaccine reduces the risk of contracting COVID-19

Sinopharm/BIBP COVID-19 vaccine reduces the risk of contracting severe COVID-19

Main efficacy outcomes of Sinopharm/BIBP COVID-19 vaccine

Contracting COVID-19 (at least 14 days following 2nd dose)

The relative risk of contracting COVID-19 in the group that received Sinopharm/BIBP COVID-19 vaccine versus the group that received placebo vaccine was 0.27 (95% CI 0.18 to 0.4). This means Sinopharm/BIBP COVID-19 vaccine reduced the risk of contracting COVID-19 by 73%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19. Comparison: Sinopharm/BIBP COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 116 people not receiving Sinopharm/BIBP COVID-19 vaccine out of 12722 presented this outcome (9 per 1000) versus 31 out of 12713 in the group that did receive it (2 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 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 high.

Contracting severe COVID-19 (at least 14 days following 2nd dose)

The relative risk of contracting severe COVID-19 in the group that received Sinopharm/BIBP COVID-19 vaccine versus the group that received placebo vaccine was 0.2 (95% CI 0.01 to 4.17). This means Sinopharm/BIBP COVID-19 vaccine reduce the risk of contracting severe COVID-19 by 80%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting severe COVID-19. Comparison: Sinopharm/BIBP COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 2 people not receiving Sinopharm/BIBP COVID-19 vaccine out of 12737 presented this outcome (16 per 100000) versus 0 out of 12726 in the group that did receive it (3 per 100000). In other words, 13 less people per 100000 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 0.013%, or that the intervention reduced the risk of contracting severe COVID-19 by 0.013 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 7692. Which means that 7692 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 low. The certainty of the evidence is based in the following judgments: Risk of bias: no concerns; Inconsistency: no concerns; Indirectness: the information available is based on a short term follow-up; Imprecision: the information provides from a small sample; Publication bias: no concerns.

Mortality

The existing evidence does not allow to assess the impact of Sinopharm/BIBP 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 (Female) (at least 14 days following 2nd dose)

The relative risk of contracting covid-19 in women in the group that received Sinopharm/BIBP COVID-19 vaccine versus the group that received placebo vaccine was 0.24 (95% CI 0.07 to 0.86). This means Sinopharm/BIBP COVID-19 vaccine reduce the risk of contracting covid-19 in women by 76%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting covid-19 in women . Comparison: Sinopharm/BIBP COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 12 people not receiving Sinopharm/BIBP COVID-19 vaccine out of 1932 presented this outcome (6 per 1000) versus 3 out of 1976 in the group that did receive it (1 per 1000). In other words, 5 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 0.5%, or that the intervention reduced the risk of contracting covid-19 in women by 0.5 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 200. Which means that 200 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 low. The certainty of the evidence is based in the following judgments: Risk of bias: no concerns; Inconsistency: no concerns; Indirectness: the information available is based on a short term follow-up; Imprecision: the information provides from a small sample; Publication bias: no concerns.

Contracting COVID-19 (Males) (at least 14 days following 2nd dose)

The relative risk of contracting covid-19 in males in the group that received Sinopharm/BIBP COVID-19 vaccine versus the group that received placebo vaccine was 0.22 (95% CI 0.13 to 0.36). This means Sinopharm/BIBP COVID-19 vaccine reduce the risk of contracting covid-19 in males by 78%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting covid-19 in males. Comparison: Sinopharm/BIBP COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 83 people not receiving Sinopharm/BIBP COVID-19 vaccine out of 10805 presented this outcome (8 per 1000) versus 18 out of 10706 in the group that did receive it (2 per 1000). In other words, 6 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 0.6%, or that the intervention reduced the risk of contracting covid-19 in males by 0.6 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 167. Which means that 167 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 low. The certainty of the evidence is based in the following judgments: Risk of bias: no concerns; Inconsistency: no concerns; Indirectness: the information available is based on a short term follow-up; Imprecision: the information provides from a small sample; Publication bias: no concerns.

Contracting COVID-19 (≥60y) (at least 14 days following 2nd dose)

There was 0 event out of 198 participants in the control group of the trials and no events in the intervention group (201 participants).

No incident cases of COVID-19 occurred in participants of 60 years or more in the phase 3, randomized trial, thus efficacy was not calculated [Al Kaabi N, 2021 ].

Summary of findings (iSoF) Table

Efficacy and effectiveness of the vaccine in subgroups

Sex
Randomized trials
Similar efficacy rates were observed for men and women in the phase 3, randomized trial [Al Kaabi N, 2021 ].
The relative risk of contracting covid-19 in women in the group that received Sinopharm/BIBP COVID-19 vaccine versus the group that received placebo vaccine was 0.24 (95% CI 0.07 to 0.86). This means Sinopharm/BIBP COVID-19 vaccine reduce the risk of contracting covid-19 in women by 76%, compared with placebo vaccine [Al Kaabi N, 2021 ].
The relative risk of contracting covid-19 in males in the group that received Sinopharm/BIBP COVID-19 vaccine versus the group that received placebo vaccine was 0.22 (95% CI 0.13 to 0.36). This means Sinopharm/BIBP COVID-19 vaccine reduce the risk of contracting covid-19 in males by 78%, compared with placebo vaccine [Al Kaabi N, 2021 ].

Age
Randomized trials
No incident cases of COVID-19 occurred in participants of 60 years or more in the phase 3, randomized trial, thus efficacy was not calculated [Al Kaabi N, 2021 ].

Other comparative studies
Zhang YT et al. included 1440 people aged 60 years and over with hypertension and diabetes mellitus who received two doses of Sinopharm/BIBP COVID-19 vaccine. Data were collected before vaccination and 28 days after the second dose. The study showed that the positive conversion rate was 100% for all Sinopharm/BIBP COVID-19 vaccine recipients. The post-inoculation GMT of the COVID-19 neutralizing antibodies were: 73.41 in the hypertension group, 69.93 in the diabetes group, 73.84 incombined disease group, and 74.86 in the healthy group[Yun Tao Zhang, 2022 ].
    
Children and adolescents
Randomized trials
Xia et al. conducted a randomized, double-blind, controlled phase 1/2 trial in China, to evaluate safety and immunogenicity of BIBP vaccine in people younger than 18 years. It was registered with clinical trial number ChiCTR2000032459. 288 participants were stratified according to age (3-5, 6-12 or 13-17 years), then randomized to receive three doses of 2 μg, 4 μg, or 8 μg of vaccine or control (1:1:1:1) 28 days apart. The neutralizing antibody GMT against the SARS-CoV-2 virus ranged from 105.3 (95% CI, 90.9-122.0) to 180.2 (95% CI, 163.7-198.5) in the 3–5 years cohort, 84.1 (95% CI, 72.6-97.3) to 168.6 (95% CI, 152.0-187.1) in the 6–12 years cohort, and 88.0 (95% CI, 77.9-99.5) to 155.7 (95% CI, 137.4-176.5) in the 13–17 years cohort on day 28 after the second vaccination. [Xia S, 2021 ]

Other comparative studies
González S et al was a retrospective cohort study conducted in Argentina including 1,536,435 participants: 689,552 in the BIBP vaccine group and 846,883 in the mRNA vaccine group (539,093 with Pfizer/Pfizer schedule, 15,552 with Pfizer/Moderna schedule and 44,862 with Moderna/Pfizer schedule. mRNA-1273 and BNT162b2 vaccines were administered to 12−17- year subjects; and BBIBP-CorV to 3−11-year subjects. Vaccine effectiveness for the BBIBP-CorV vaccine group was 76.4% (95% CI 62.9 to 84.5) for the 3−11 age subgroup. [González S, 2022 ]

Castelli JM et al was a test negative case control study conducted in Argentina that included 844,460 children and adolescents without previous SARS-CoV-2 infection eligible to receive a primary vaccination schedule. Vaccine effectiveness for the BBIBP-CorV primary schedule was 61.2% (95% CI, 56.4% to 65.6%) during the Delta predominance period, and 16.0% (95% CI,13.2% to 18.6%) during the Omicron predominance period. [Castelli JM, 2022 ]

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

Breastfeeding
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 ]. 

Vaccine effectiveness (other comparative studies)

Contracting COVID-19
Alireza Mirahmadizadeh et al. was a cohort study conducted in Iran. The study enrolled 1,882,148 participants: 881,638 vaccine group; 1,000,510 control group. Based on data derived from administrative repositories during mass-vaccination campaigns or programs between February 09th and the end of follow-up in October 22th 2021; the study results showed a vaccine effectiveness of 79.9% (95% CI, 79% to 80.4%) against infection, 71.9% (95% CI, 70.7 %to 73.1%) against hospitalization and 86.1% (95% CI, 84.1% to 88.0%) against death [Alireza Mirahmadizadeh, 2022 ].

Belayachi J et al. was a case-control study conducted in Morocco that included 25,768 participants: 12,884 RT-PCR-positive cases and 12,885 controls using data from the national laboratory COVID-19 database and the national vaccination register from February to October 2021 in Morocco. Vaccine effectiveness was 88% (95% CI, 84% to 91%) 1 to 30 days after the second dose of Sinopharm/BIBP, and 64% (95% CI, 59% to 69%) ≥150 days after [Belayachi J, 2022 ].

Rearte A et al. was a case control study conducted in Argentina. The study included 237,330 individuals in the analysis of BBIBP-CorV vaccine: 95,519 in the case group and 141,811 in the control group. The study assessed the effectiveness of three vaccines (rAd26-rAd5, ChAdOx1 nCoV-19, and BBIBP-CorV) on SARS-CoV-2 infection and risk of death in people with RT-PCR confirmed COVID-19, using data from the National Surveillance System (SNVS 2.0). All individuals aged 60 years or older reported to SNVS 2.0 as being suspected to have COVID-19 who had disease status confirmed with RT-PCR were included in the study. The odds ratio of the BBIBP-CorV vaccine on the risk of SARS-CoV-2 infection in individuals with only one dose was OR 0.77 (95% CI 0.75 to 0.80). After the second dose was OR 0.56 (95% CI 0.55 to 0.58) [Rearte A, 2022 ].

Petrovic V et al. was a study conducted in Serbia, including 117,914 participants with two BBiBP vaccines and 241,166 controls. Based on data from the surveillance registry from Vojvodina and the nationwide COVID-19 vaccine registry, participants aged 60 and above, between December 24, 2020 and April 28, 2021. The overall effectiveness of BBIBP was 86% (95% CI 86 to 87.7) and 85.8% (95% CI 84.8 to 86.8) against mild COVID-19. [Petrovi? V, 2022 ]

Silva-Valencia et al. conducted a retrospective cohort study to assess the effectiveness of BIBP-CorV vaccines in preventing COVID-19 infection and mortality in Peru. 606,772 health care workers (HCW) were elegible, of which 22.9% had not received any dose, 9.3% had received only one dose an 67.8% had received two doses of the vaccine. Vaccine Effectiveness among those who received two doses of the vaccine was 47.6% (95% CI, 46.3% to 48.9%) for preventing SARS-CoV-2 infection. [ Silva-Valencia, 2022 ]

Contracting severe COVID-19
Alireza Mirahmadizadeh et al. was a cohort study conducted in Iran. The study enrolled 1,882,148 participants: 881,638 vaccine group; 1,000,510 control group. Based on data derived from administrative repositories during mass-vaccination campaigns or programs between February 09, 2021 and the end of follow-up in October 22, 2021; the study results showed a vaccine effectiveness of 79.9% (95%CI 79. to -80.4%) against infection, 71.9% (95%CI 70.7 to 73.1%) against hospitalization and 86.1% (95%CI 84.1-88.0%) against death [Alireza Mirahmadizadeh, 2022 ].

Belayachi J et al. was a case-control study conducted in Morocco that included 25,768 participants: 12,884 RT-PCR-positive cases and 12,885 controls using data from the national laboratory COVID-19 database and the national vaccination register from February to October 2021 in Morocco. Vaccine effectiveness against hospitalization in adults aged 18 to 64 years was 88% (95% CI, 82% to 92%) 1-30 days after the second dose of Sinopharm/BIBP, and 70% (95% CI, 57% to 79%) measured ≥150 days after. [Belayachi J, 2022 ]

Petrovic V et al. was a study conducted in Serbia, including 117,914 participants with two BBiBP vaccines and 241,166 controls. Based on data from the surveillance registry from Vojvodina and the nationwide COVID-19 vaccine registry, participants aged 60 and above, between December 24, 2020 and April 28, 2021. The effectiveness of BBIBP was 90.5% (95% CI 88.9 to 91.9) against severe COVID-19 [Petrovi? V, 2022 ].

Al-Momani et al was a case-control study conducted in Jordan that evaluated the effectiveness of Pfizer-BioNTech and BBIBP-CorV vaccines against COVID-19-related hospitalization among adult participants in the Prince Hamza Hospital between February and April 2022. The effectiveness of the BBIBP-CorV vaccine against hospitalization was 67% (95% CI, 52% to 78%). [Al-Momani H, 2022 ]

Silva-Valencia et al. conducted a retrospective cohort study to assess the effectiveness of BIBP-CorV vaccines in preventing COVID-19 infection and mortality in Peru. 606,772 health care workers (HCW) were elegible, of which 22.9% had not received any dose, 9.3% had received only one dose an 67.8% had received two doses of the vaccine. Vaccine Effectiveness (VE) among those who received two doses of the vaccine was 93.3% (95% CI, 91.4% to 94.8%) for preventing all-cause mortality and 96.1% (95% CI, 94.4% to 97.4%) for preventing COVID-19 mortality. They found an effect modification of vaccine effectiveness by age group (18-59 years vs. ≥ 60 years), statistical evidence for a higher VE for full immunization HCW of 18-59 years in comparison with 60+ years for all-cause mortality (86.4% vs. 79.2%, multiple interaction p-value = 0.014) and COVID-19 mortality (93.3 vs. 83.4%, multiple interaction p-value = 0.002). [ Silva-Valencia, 2022 ]

Nittayasoot et al was a test negative case-control study to examine the effectiveness of COVID-19 vaccines during January to April 2022 in Thailand. They analyzed secondary data from four main national health data bases: Co-Lab, Co-Ward, COVID-10 Death and MOPH-IC, using the national identification numbers of each individual as a unique identifier to link the same person across databases. They obtained a total of 3,059,616 records including: 1,015 cases of COVID-19 pneumonia requiring invasive ventilation from 652,854 cases with SARS-CoV-2 detection and 2,046,762 controls or non-SARS-CoV-2 detection. Vaccine Effectiveness against pneumonia requiring invasive ventilation for BIBP + BIBP schedule was 65.81% (95% CI, 39.47% to 80.69%). [Nittayasoot N, 2022 ]

Heidarzadeh et al was a test negative case-control study to estimate the effectiveness of COVID-19 vaccines against hospitalization and death in the Guilan Province of Iran, from May to December 2021. This study included population aged 5 years and above by extracting information from local databases (MCMC and SIB). The total study population was 42,084 including 19,500 cases and 22,586 controls. For the BIBP + BIBP schedule, Vaccine Effectiveness (VE) against hospitalization (temporary admission) was 62% (95% CI, 50% to 72%) within 1-30 days and 95% (95% CI, 67% to 99.4%) ≥ 151 days after second dose. VE against hospitalization (regular admission) was 64% (95% CI, 59% to 68%) within 1-30 days and 85% (95% CI, 77% to 91%) ≥ 151 days after second dose. VE against hospitalization (ICU admission) was 28% (95% CI, -17% to 53%) within 1-30 days and 0.26 (95% CI, -77% to 69%) ≥ 151 days after second dose. VE against death was 34% (95% CI, 13% to 50%) within 1-30 days and 33% (95% CI, -4% to 69%) ≥ 151 days after second dose. [Heidarzadeh A, 2022 ]

Transmission
No studies reported or assessed this outcome

Efficacy and effectiveness against SARS-CoV-2 variants

Immunogenicity outcomes
Alpha (B.1.1.7) 
Zhang X et al. carried out a non-comparative study (neutralizing capacity from recipients' sera) in China, which included 470 healthcare workers. The study reported data from 28 days post immunization. The results showed that the vaccine-elicited sera showed complete or partial loss of neutralizing activity against lineage B.1.1.7, and the GMTs against B.1.1.7 declined 2.2-fold to 31.17 (95% CI 27.71 to 35.07) compared to their titres against wild-type strains [Zhang X, 2021 ].

Beta (B.1.351) 
Zhang X et al. carried out a non-comparative study (neutralizing capacity from recipients' sera) in China, which included 470 healthcare workers. The study reported data from 28 days post immunization. The results showed that only 42.34% vaccine-elicited sera preserved neutralizing activity against lineage B.1.351, with significantly reduced GMTs compared with their titres against wild-type strains (GMT 15.08 (95% CI 13.06 to 17.42)) [Zhang X, 2021 ].

Angkasekwinai N et al. was a cohort study conducted Thailand . Based on data from a single-center, tertiary care university-based hospital in Bangkok, between July to September 2021. Results showed that for both the Sinovac-prime and AstraZeneca-prime groups, the PRNT50 GMT against the Delta and Beta variant were significantly higher among those who received a booster dose of Pfizer (30µg or 15µg) compared to those who received AstraZeneca or Sinopharm/ BIBP. In addition, there was no statistical difference in PRNT50 between boosting with 30µg and 15µg- Pfizer regardless of the primary series vaccine and the type of variants. However, the PRNT50 against the Beta variant was in general around 1.5-fold lower than the Delta variants for both CoronaVac-prime and ChAdOx1-prime groups. The GMRs of the PRNT50 between post-boost and post-primary series were highest among the participants who received Pfizer boosting vaccination in bothSinovac-prime and AstraZeneca-prime groups. The SARS-CoV-2 RBD IgG levels and the neutralizing titers against Delta variant or Beta variant were strongly correlated.[ ].

Effectiveness outcomes
Delta (B.1.617.2) 
Lin XN et al. conducted a case-control study (test-negative) in China, which included 74 positive cases for SARS-COV-2 and 292 controls. In the study, they evaluated the efficacy of the Sinovac and Sinopharm vaccines (BIBP and WIBP) against COVID-19 infection for 14 days or more after receiving the second dose. The results showed that the effectiveness against COVID-19 infection was 59.0% (95% CI 16.0 to 81.6) and the effectiveness against severe COVID-19 infection was 100%. [Li XN, 2021 ]

Kang et al. was a comparative cohort study in China that included 10,805 healthy adults. The study evaluated the efficacy of the inactivated virus vaccines Sinovac and Sinopharm/BIBP against COVID-19 infection for 14 days or more after receiving the second dose. Results show an effectiveness against symptomatic COVID-19 infection of 63.5% (CI, 37.2% to 89.8%) and 100.0% (CI, 98.4% to 100.0%) against severe COVID-19 infection. [Kang M, 2022 ]

Castelli JM et al was a test negative case control study conducted in Argentina that included 844,460 children and adolescents without previous SARS-CoV-2 infection eligible to receive a primary vaccination schedule. Vaccine effectiveness for the BBIBP-CorV primary schedule was 61.2% (95% CI, 56.4% to 65.6%) during the Delta predominance period. [Castelli JM, 2022 ]

Omicron (B.1.1.529.1)
Ng O et al, was a cohort study conducted in Singapore, the study included data from the Singapore Ministry of Health’s official COVID-19 database, including individuals who had received 2 or 3 doses of mRNA vaccines (by Pfizer-BioNTech or Moderna) or inactivated vaccines (by Sinovac or Sinopharm) and notified infections from December 27, 2021, to March 10, 2022. The study showed an effectiveness during the Omicron wave with an incidence rate ratio for 2 doses of CoronaVac of 1.03% (95% CI 0.95-1.11) and 3 doses of 0.93% (95% CI 0.89-0.97) against confirmed infection. The incidence rate ratio for 2 doses of CoronaVac of 1.81% (95% CI 1.20 - 2.74) and 3 doses of 0.30% (95% CI 0.18 - 0.51) against severe infection. [Ng OT, 2022 ].

González S et al was a retrospective cohort study conducted in Argentina including 1,536,435 participants: 689,552 in the BIBP vaccine group and 846,883 in the mRNA vaccine group (539,093 with Pfizer/Pfizer schedule, 15,552 with Pfizer/Moderna schedule and 44,862 with Moderna/Pfizer schedule. mRNA-1273 and BNT162b2 vaccines were administered to 12−17 year subjects; and BBIBP-CorV to 3−11-year subjects. Vaccine effectiveness for the BBIBP-CorV vaccine group was 76.4% (95% CI 62.9 to 84.5) for the 3−11 age subgroup [González S, 2022 ].

Soledad Gonzalez et al was a test-negative, case-control study conducted in Argentina. The study included 422,144 individuals ≥50 years: 221,933 with positive test and 200,211 with negative test. The aim of the study was to estimate the protection against laboratory-confirmed SARS-CoV-2 infection, hospitalisations, and death after homologous or heterologous third-dose (booster) in individuals with primary vaccination schemes with rAd26-rAd5, ChAdOx1nCoV-19, BBIBP-CorV or heterologous combinations, during the period of Omicron BA.1 predominance. Odds ratio of booster dose against confirmed SARS-CoV-2 infections were 0.62 (95% CI 0.55 to 0.69) for BBIBP-CorV primary schedule and mRNA booster (≤ 60 days), and 0.71 (95% CI 0.67 to 0.75) for BBIBP-CorV primary schedule and vectored booster (≤ 60 days). Odds ratio of booster dose against hospitalizations were 0.22 (95% CI 0.09 to 0.51) for BBIBP-CorV primary schedule and mRNA booster (≤ 60 days), and 0.24 (95% CI 0.17 to 0.34) for BBIBP-CorV primary schedule and vectored booster (≤ 60 days). [Soledad Gonzalez, 2022 ]

Castelli JM et al was a test negative case control study conducted in Argentina that included 844,460 children and adolescents without previous SARS-CoV-2 infection eligible to receive a primary vaccination schedule. Vaccine effectiveness for the BBIBP-CorV primary schedule was 16.0% (95% CI,13.2% to 18.6%) during the Omicron predominance period. [Castelli JM, 2022 ]

Albreiki M et al was a case control study conducted in the United Arab Emirates that included data from 4,618 participants: 541 hospitalized and 4,077 non hospitalized. The aim was to assess the effectiveness against hospitalization of the Sinopharm and Pfizer vaccines between May 28th 2021 and January 13th 2022, during the Delta and Omicron outbreaks. Vaccine effectiveness (VE) against hospital admission during the Omicron outbreak was 90% (95% CI, 74% to 96%) for ≤ 45 years and 58% (95% CI, 0% to 87%) for participants older than 45 years. VE against hospital admission during the Delta outbreak was 94% (95% CI, 90% to 97%) for ≤ 45 years and 92% (95% CI, 88% to 95%) for participants older than 45 years. [Albreiki M, 2023 ]

Vaccine efficacy and effectiveness for booster dose

Immunogenicity outcomes
Yu, X et al. was a before-after study conducted in China. The study enrolled 292 participants and study determined the serum neutralizing activity using a pseudovirus-based neutralization assay after the third booster in healthcare workers in Shanghai Ruijin Hospital aged 18-59 years, who have received priming vaccination by two doses for at least 8 months. Outcome measured 28 after the booster dose. The results showed a Median antibody level of 486.66 (296.16-681.91), a seroconversion rate of 98.29% and a GMT increased to 294.85 (95% CI 252.99-343.65) [Yu, X., 2021 ].

BOOST was a phase 4 non-randomized study conducted in China. The study enrolled 103 healthy adults aged 18-59 years and analyzed the immune response and reactogenicity of a third-dose homologous Sinopharm/ BIBP boosting vaccination. The results showed a third homologous Sinopharm/BIBP boosting vaccination was highly immunogenic for healthy adults. Median anti-RBD antibody and IgG level significantly increased from 11.12 BAU/ml to 2607.50 BAU/ml and 4.07 BAU/ml to 619.20 BAU/ml on day 14 [Ai J, 2022 ].

Zhang Y et al. was a before-after study conducted in China. The study enrolled 136 participants aged 18 to 63 years and assessed safety and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses of a third-dose homologous BBIBP-CorV boosting vaccination. The study results showed that neutralizing antibody titers rapidly increased all subjects within the first month, from 18.3 at day 3 to 439.8 at day 28 (24-fold increase, GMT). The rate of neutralizing antibody titers increase appeared to be relatively constant during the first 14 days and then declined between day 14 and day 28, suggesting that the neutralizing antibody titers might reach a plateau level in about a month. Neutralizing antibody titers at day 28 post the third dose (GMT: 439.8) were higher than those at month 3 after the first dose (GMT: 91.1), a 4.83-fold increase [Zhang Y, 2022 ].

Cheng et al was a comparative study conducted in China, The study recruited 353 participants who received a primary vaccination regimen consisting of two Sinopharm/BBIBP vaccines plus a booster dose of the same vaccine 7 months from the first dose. Vaccine elicited antibody levels were measured before and after the first, second and booster dose. Results found IgA levels remained low throughout the study. IgM, IgG and neutralizing antibodies reached a peak level after primary vaccination that slowly declined over time. The booster dose increased levels of IgM to post dose 1 levels. IgG levels increased by a factor of 21.4-30.0 (25.2-35.8) post booster dose. Neutralizing titers had a 4.5 fold increase after the booster vaccination, 32.94 (95% CI: 24.22–44.81), when compared to initial peak at month 2, 6.80 (95% CI: 5.98–7.72). [Cheng ZJ, 2022 ].

Xia et al. conducted a randomized, double-blind, controlled phase 1/2 trial in China, to evaluate safety and immunogenicity of BIBP vaccine in people younger than 18 years. It was registered with clinical trial number ChiCTR2000032459. 288 participants were stratified according to age (3-5, 6-12 or 13-17 years), then randomized to receive three doses of 2 μg, 4 μg, or 8 μg of vaccine or control (1:1:1:1) 28 days apart. The neutralising antibody GMT against the SARS-CoV-2 virus and ranged from 143.5 (95% CI, 124.3-165.8) to 224.4 (95% CI, 202.2-249.1) in the 3–5 years cohort, 127 (95% CI, 112.0-144.2) to 184.8 (95% CI, 162.5-210.1) in the 6–12 years cohort, and 150.7 (95% CI, 134.2-169.4) to 199 (95% CI, 180.6-219.2) in the 13–17 years cohort on day 28 after the third vaccination. [Xia S, 2021 ]

Effectiveness outcomes
Ng O et al, was a cohort study conducted in Singapore, the study included data from the Singapore Ministry of Health’s official COVID-19 database, including individuals who had received 2 or 3 doses of mRNA vaccines (by Pfizer-BioNTech or Moderna) or inactivated vaccines (by Sinovac or Sinopharm) and notified infections from December 27, 2021, to March 10, 2022. The study showed an effectiveness during the Omicron wave with an incidence rate ratio for 3 doses of CoronaVac of 0.93% (95% CI 0.89-0.97) against confirmed infection and 69.7% (95% CI 48.9 - 82.0) against severe infection. [Ng OT, 2022 ]

Park S et al was a cohort study conducted in the United Arab Emirates that included 495 participants, 121 who received a BIBP primary schedule only, 326 who received Pfizer booster dose and 48 who received a homologous BIBP booster dose. All healthcare workers who had completed two doses of the BBIBP-CorV vaccine between November 2020 and September 2021 in the Sheikh Khalifa Specialty Hospital were elegible. The Odds Ratio for SARS-CoV2 infection after BIBP booster was 0.446 (95% CI, 0.170-1.167) [Park S, 2022 ]

Heidarzadeh et al was a test negative case-control study to estimate the effectivenesss of COVID-19 vaccines against hospitalization and death in Guilan Province of Iran, from May to December 2021. This study included population aged 5 years and above by extracting information from local databases (MCMC and SIB). The total study population was 42,084 including 19,500 cases and 22,586 controls. For the BIBP + BIBP + BIBP schedule, vaccine effectiveness against hospitalization (regular admission) was 96% (95% CI, 92% to 98%) and against death was 58% (95% CI, -6% to 83%). [Heidarzadeh A, 2022 ]

Vaccine efficacy and effectiveness for heterologous schedule

Immunogenicity outcomes
Angkasekwinai N et al. was a cohort study conducted Thailand. Based on data from a single-center, tertiary care university-based hospital in Bangkok, between July to September 2021. Results showed that heterologous boosting vaccination with Pfizer following Sinovac or AstraZeneca primary series is the most immunogenic against SARS-CoV-2 variants. A lower dose Pfizer may be used as a booster in settings with limited vaccine supply.[ ].

Macchia et al, was a non-inferiority randomized clinical trial conducted in Argentina. The study compared the immune response generated by homologous Sputnik V regimen to the heterologous regimens of Sputnik V vaccine with either Moderna, Sinopharm BIBP or AstraZeneca vaccines. Macchia et al, recruited 540 individuals with no history of COVID-19 infection who had received a first dose of the Sputnik V vaccine (component rAd26) at least 30 days prior. Participants were randomized to receive a second dose of either Sputnik V (component rAd26 or rAd5), AstraZeneca, Moderna or Sinopharm BIBP vaccines. The study showed all but the Moderna regimen were statistically inferior to the standard Sputnik V regimen (rAd26/rAd5). The Moderna regimen showed a 3.53 fold increase in antibody concentrations compared to the standard Sputnik V regimen [Macchia A, 2022 ].

Wang X et al was a cohort study conducted in China including 403 individuals between 18 and 59 years old: 275 Sinopharm/WIBP (WIBP-CorV) + Sinopharm/BIBP (BIBP-CorV) recipients, and 133 Sinopharm/BIBP + Sinopharm/BIBP recipients. The study compared the immunogenicity of both primary schedules. Sera of participants was obtained 1, 2, and 6 months after the second doses, and neutralizing antibody titers were measured. The GMT of neutralizing antibodies at 1 month was 21.33 (95% CI, 19.62–23.18) in the WIBP+BBIBP group and 22.45 (95% CI, 20.16–24.99) in the BBIBP+BBIBP group. At 2 months GMT was 16.80 (95% CI, 15.28–18.47) in the WIBP+BBIBP group and 19.28 (95% CI, 17.48–21.25) in the BBIBP+BBIBP group. At 6 months GMT was 3.56 (95% CI, 3.28–3.86) in the WIBP+BBIBP group and 5.36 (95% CI, 4.56–6.31) in the BBIBP+BBIBP. [Wang X, 2022 ].

Vaccine efficacy and effectiveness for heterologous booster schedule

Immunogenicity outcomes
Angkasekwinai N et al. was a cohort study conducted Thailand . Based on data from a single-center, tertiary care university-based hospital in Bangkok, between July to September 2021. Results showed that heterologous boosting vaccination with Pfizer following Sinovac or AstraZeneca primary series is the most immunogenic against SARS-CoV-2 variants. A lower dose Pfizer may be used as a booster in settings with limited vaccine supply. [ ]

Biyan Zhang et al. was a cohort study conducted in Singapore. The study enrolled 52 participants and evaluated the levels of antibodies for Omicron variant and compared to the ancestral strain (Wuhan-Hu-1) and Delta variant, in four groups of volunteers receiving 1) Two doses of mRNA vaccines plus an mRNA vaccine booster (Homologous mRNA vaccine booster) 2) Two doses of inactivated virus vaccines plus an inactivated virus vaccine booster (Homologous inactivated virus vaccine booster) 3) Two doses of mRNA vaccines plus an inactivated virus vaccine booster (Heterologous inactivated virus vaccine booster) and 4) Two doses of inactivated virus vaccines plus an mRNA vaccine booster (Heterologous mRNA vaccine booster). The study results showed that only the mRNA vaccine booster was able to effectively increase the median levels of neutralizing capabilities against the Omicron variant (Group 1, median 90.45% [IQR 78.71-94.33%]; Group 4, median 77.85% [IQR 47.80-92.18%]) by 4.5-fold and 3-fold, respectively. Inactivated virus booster shot was unable to significantly increase the median levels of neutralizing capabilities against the Omicron variant regardless of whether the individuals received 2 priming doses of mRNA vaccines (Group 3, median 30.65% [IQR 19.98- 36.03%]) or 2 priming doses of inactivated virus vaccines (Group 4, median 26.80% [IQR 18.35- 36.15%]). [Biyan Zhang, 2022 ]

Zhu Y et al was a cohort study conducted in China, including 486 participants with heterologous prime-boost inactivated vaccine schedules: 48 received BBIBP+CoronaVac, 30 received CoronaVac+BBIBP, 30 received CoronaVac+WIBP, 34 received WIBP+CoronaVac, 25 received WIBP+BBIBP and 36 received BBIBP+WIBP. The study evaluated the immunogenic response of heterologous booster schedules with inactivated vaccines. The neutralization GMTs against the ancestral strain were 312 in the BBIBP+CoronVac group, 179 in the CoronaVac+BBIBP group, 335 in the CoronaVac+WIBP group, 444 in the WIBP+CoronaVac group, 130 in the WIBP+BBIBP group and 191 in the BBIBP+WIBP group. [Zhu Y, 2022 ]

Effectiveness outcomes
Soledad Gonzalez et al was a test-negative, case-control study conducted in Argentina. The study included 422,144 individuals ≥50 years: 221,933 with positive test and 200,211 with negative test. The aim of the study was to estimate the protection against laboratory-confirmed SARS-CoV-2 infection, hospitalisations, and death after homologous or heterologous third-dose (booster) in individuals with primary vaccination schemes with rAd26-rAd5, ChAdOx1nCoV-19, BBIBP-CorV or heterologous combinations, during the period of Omicron BA.1 predominance. Odds ratio of booster dose against confirmed SARS-CoV-2 infections were 0.62 (95% CI, 0.55-0.69) for BBIBP-CorV primary schedule and mRNA booster (≤ 60 days), and 0.71 (95% CI, 0.67-0.75) for BBIBP-CorV primary schedule and vectored booster (≤ 60 days). Odds ratio of booster dose against hospitalizations were 0.22 (95% CI, 0.09-0.51) for BBIBP-CorV primary schedule and mRNA booster (≤ 60 days), and 0.24 (95% CI, 0.17-0.34) for BBIBP-CorV primary schedule and vectored booster (≤ 60 days). [Soledad Gonzalez, 2022 ]

Park S et al was a cohort study conducted in the United Arab Emirates that included 495 participants, 121 who received a BIBP primary schedule only, 326 who received Pfizer booster dose and 48 who received an homologous BIBP booster dose. All healthcare workers who had completed two doses of the BBIBP-CorV vaccine between November 2020 and September 2021 in the Sheikh Khalifa Specialty Hospital were eligible. The Odds Ratio for SARS-CoV2 infection after a BIBP primary schedule and a Pfizer-BioNTech booster was 0.401 (95% CI, 0.187-0.86). [Park S, 2022 ]

Nittayasoot et al was a test negative case-control study to examine the effectiveness of COVID-19 vaccines during January to April 2022 in Thailand. They analyzed secondary data from four main national health data bases: Co-Lab, Co-Ward, COVID-10 Death and MOPH-IC, using the national identification numbers of each individual as a unique identifier to link the same person across databases. They obtained a total of 3,059,616 records including: 1,015 cases of COVID-19 pneumonia requiring invasive ventilation from 652,854 cases with SARS-CoV-2 detection and 2,046,762 controls or non-SARS-CoV-2 detection. Vaccine Effectiveness against pneumonia requiring invasive ventilation for BIBP + BIBP + Pfizer schedule was 81.37% (95% CI, 36.08% to 94.57%}). [Nittayasoot N, 2022 ]

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

Main safety outcomes of Sinopharm/BIBP COVID-19 vaccine

Any adverse event (at least 7 days after any injection)

The relative risk of any adverse event in the group that received Sinopharm/BIBP COVID-19 vaccine versus the group that received placebo vaccine was 0.91 (95% CI 0.89 to 0.94). No statistically significant differences between groups were found for any adverse events.

Figure - Forest plot of risk ratio meta-analysis. Outcome: any adverse event. Comparison: Sinopharm/BIBP COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 6250 people not receiving Sinopharm/BIBP COVID-19 vaccine out of 6250 presented this outcome (465 per 1000) versus 5623 out of 13471 in the group that did receive it (418 per 1000). In other words, 47 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 4.7%, or that the intervention reduced the risk of any adverse event by 4.7 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 21. Which means that 21 people need to receive the vaccine for one of them to experienced any adverse event.

Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.

Local adverse event (at least 7 days after any injection)

The relative risk of local adverse event in the group that received Sinopharm/BIBP COVID-19 vaccine versus the group that received placebo vaccine was 0.71 (95% CI 0.68 to 0.74). No statistically significant differences between groups were found for any adverse events.

Figure - Forest plot of risk ratio meta-analysis. Outcome: local adverse event. Comparison: Sinopharm/BIBP COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 3906 people not receiving Sinopharm/BIBP COVID-19 vaccine out of 13453 presented this outcome (290 per 1000) versus 2786 out of 13471 in the group that did receive it (207 per 1000). In other words, 83 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 8.3%, or that the intervention reduced the risk of local adverse event by 8.3 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 12. Which means that 12 people need to receive the vaccine for one of them to experienced local adverse event.

Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.

Systemic adverse event (at least 7 days after any injection)

The relative risk of systemic adverse event in the group that received Sinopharm/BIBP COVID-19 vaccine versus the group that received placebo vaccine was 1.02 (95% CI 0.98 to 1.06). This means Sinopharm/BIBP COVID-19 vaccine increase the risk of systemic adverse event by 2%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: systemic adverse event. Comparison: Sinopharm/BIBP COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 3743 people not receiving Sinopharm/BIBP COVID-19 vaccine out of 13453 presented this outcome (278 per 1000) versus 3810 out of 13471 in the group that did receive it (283 per 1000). In other words, 5 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 0.5%, or that the intervention increased the risk of systemic adverse event by 0.5 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 200. Which means that 200 people need to receive the vaccine for one of them to experienced systemic adverse event.

Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.

Serious adverse event (SAEs) (at least 7 days after any injection)

The relative risk of serious adverse event (saes) in the group that received Sinopharm/BIBP COVID-19 vaccine versus the group that received placebo vaccine was 0.76 (95% CI 0.54 to 1.06). No statistically significant differences between groups were found for serious adverse events.

Figure - Forest plot of risk ratio meta-analysis. Outcome: serious adverse event (saes). Comparison: Sinopharm/BIBP COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 78 people not receiving Sinopharm/BIBP COVID-19 vaccine out of 13453 presented this outcome (6 per 1000) versus 59 out of 13471 in the group that did receive it (5 per 1000). In other words, 1 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 0.1%, or that the intervention reduced the risk of serious adverse event (saes) by 0.1 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 1000. Which means that 1000 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.

Summary of findings table (iSoF)

Safety of the vaccine in subgroups

Sex
Randomized trials
The safety profile of the Sinopharm/BBIBP vaccine against COVID-19 was not evaluated in all gender 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
No data are available for this subgroup

Other comparative studies
Thonginnetra et al. conducted a prospective cohort single center trial at Chulabhorn Hospital, Thailand, from 20th September to 11th November, 2021. A total of 36,808 adolescents between the ages of 10 and 17 were enrolled in the study. Participants were scheduled to receive two doses of BBIBP-CorV through intramuscular administration with a 21–28-day interval between doses.  Among participants, 76% (27,880) reported reactogenicity within the first 24 hours and 7 days following the first dose. Half (51.41%) of participants experienced pain at the injection site; the majority of cases were mild in severity. Injection site tenderness (37.93%) was another common local reaction. Fatigue (37.89%), myalgia (33.56%), and headache (26.76%) were the most common systemic reactions. On days 2–7 after the first dose, 25.85% of participants experienced adverse reactions. Following the second dose, reactogenicity was 7.6% and 1.09% within 24 h and between days 2–7. The majority of reactions were of mild to moderate severity. [Thonginnetra S, 2022 ]

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

Other comparative studies
Huang et al. was a retrospective cohort study conducted in China [Huang J, 2022 ] at the Center for Reproductive Medicine, Jiangxi Maternal and Child Health Hospital (JMCHH) affiliated with Nanchang University School of Medicine. This study investigated the effect of female inactivated SARS-CoV-2 vaccination on cycle characteristics, laboratory parameters and pregnancy outcomes during in vitro fertilization (IVF) treatment. Participants included women who underwent fresh IVF cycles between June 1st and September 13th 2021 and who were followed up to October 18th 2021. The number of oocytes retrieved (9.9 ± 7.1 vs 9.9 ± 6.7), good-quality embryo rate (33.5 ± 29.8% vs 29.9 ± 28.6%) and clinical pregnancy rate (59.1% vs 63.6%) were all similar between the vaccine group and the control group. Additionally, no significant differences were observed regarding other cycle characteristics, laboratory parameters and pregnancy outcomes such as: stimulation duration, total gonadotropin dose, serum sex hormone level, endometrial thickness, number of ≥14 mm follicles on trigger day, mature oocyte rate, fertilization rate, cleavage rate, blastocyst formation rate, available blastocyst rate, biochemical pregnancy (65.2% vs 73.7%) and implantation (45.4% vs 46.7%). Results were also similar when vaccinated patients were subdivided into three categories based on the time interval from complete vaccination to cycle initiation: ≤1 month, >1–2 months, and >2 months. The authors suggest that inactivated SARS-CoV-2 vaccines in females did not result in any measurable detrimental effects on IVF treatment. However, further prospective studies with larger cohort size and longer follow-up are needed to validate this conclusion. [Huang J, 2022 ]

Ali et al conducted a cross sectional study in Iran, from January to March 2022, and included 1645 pregnant women. All vaccinated women received the Sinopharm vaccine. The risk of maternal morbidities was not significantly different in two groups (p > 0.001). Only the risk of neonatal intensive care unit admission was higher in vaccinated women was higher in vaccinated women than in non-vaccinated women (OR = 3.39, p < 0.001). [Ali H, 2022 ]

Breastfeeding
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 ].