|Ahead of print publication
Corbevax vaccine side effects in children of age group 12–14 years: A prospective observational study
Kumar Pushkar, Saurabh Bobdey, Rituraj Kotoki, Kunal Koundinya, Priyanka Sharma Michael, SK Kaushik
Department of Community Medicine, AFMC, Pune, Maharashtra, India
|Date of Submission||29-Sep-2022|
|Date of Decision||03-Oct-2022|
|Date of Acceptance||17-Oct-2022|
|Date of Web Publication||18-Feb-2023|
Department of Community Medicine, AFMC, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Corbevax was introduced by the Government of India in March 2022 for the vaccination of children between 12 and 14 years, however, there is a dearth of literature providing side effect profiles of Corbevax in the real-world/community. Hence, this study was conducted to assess the incidence and types of adverse events following immunization (AEFI) of Corbevax vaccine. Materials and Methods: A prospective observational study was conducted among 358 children between 12 and 14 years of age who had received Corbevax vaccine at a tertiary care center in western Maharashtra from March 16 to May 31, 2022. The participants were followed-up telephonically for side effects at 24 h, 72 h, and 7 days following the first dose and second doses of vaccinations. Results: Out of 358 children of age 12–14 years who received Corbevax vaccine, almost 80% of vaccines developed mild AEFI. Overall, reactogenicity was higher after the second dose and the most common AEFI was pain in the abdomen, followed by headache and pain at the site of injection. Occurrence of AEFI after the first dose (odds ratio: 158.87, 95% confidence interval 46.58–528.28, P < 0.005) was found to be a risk factor for the development of AEFI after the second dose. Conclusion: Corbevax was introduced in India for children between 12 and 14 years, but to the best of our knowledge, till date, there is no study specifically focused of AEFI due to Corbevax in the community setting. The study findings indicate that Corbevax is a safe vaccine with few mild side effects, thus reinforcing faith in the safety profile of the vaccine.
Keywords: 1st and 2nd dose, adverse event following immunizations, Corbevax, coronavirus disease 19 vaccination
|How to cite this URL:|
Pushkar K, Bobdey S, Kotoki R, Koundinya K, Michael PS, Kaushik S K. Corbevax vaccine side effects in children of age group 12–14 years: A prospective observational study. J Mar Med Soc [Epub ahead of print] [cited 2023 Mar 24]. Available from: https://www.marinemedicalsociety.in/preprintarticle.asp?id=369950
| Introduction|| |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the deadly virus that causes coronavirus disease 19 (COVID-19) has rampantly spread over the globe. The pandemic has diseased millions of people, till date, there have been 529,410,287 confirmed cases of COVID-19, including 6,296,771 deaths, reported by WHO. To combat this deadly disease, the world went into overdrive for the development of vaccines, and by early 2021, mass vaccination drives were adopted by numerous countries across the globe. As of May 31, 2022, a total of 11,947,644,522 vaccine doses have been administered.
Researchers worked enormously to develop effective and safer vaccines against COVID-19 infection. Before COVID-19, a vaccine for an infectious disease had never been produced in less than several years– and no vaccine existed for preventing a coronavirus infection in humans. However, vaccines have been produced against several animal diseases caused by coronaviruses, including infectious bronchitis virus in birds, canine coronavirus, and feline coronavirus. Previous projects to develop vaccines for viruses in the family Coronaviridae that affect humans have been aimed at SARS and Middle East respiratory syndrome (MERS). Few of the earliest COVID-19, vaccine candidates were mRNA molecule and viral vector vaccines. As multiple COVID-19 vaccines were authorized or licensed for use, the real-world effectiveness and side effect profile of various vaccines is being assessed.
No studies have been conducted so far for the adverse event following immunization (AEFI) incidence for Corbevax vaccine among adolescents and children; however, little has been known about the same from other types of COVID-19 vaccine such as mRNA, DNA, and inactivated virus vaccine. A study by Frenck et al. reported that the incidence of overall AEFI in the BNT162b2 vaccine (mRNA vaccine) and placebo groups was 6.0% and 5.9%, respectively. Furthermore, a study by Ali et al. found a significantly increased incidence of adverse reactions after vaccination in mRNA-1273 vaccine recipients (dose 1: 95.9% and dose 2: 97.1%) compared with placebo recipients (dose 1: 65.1% and dose 2: 55.7%). Similarly, a study by Han's et al. showed that the incidence of overall AEFI with the use of CoronaVac (inactivated virus vaccine) ranged from 18% to 35% after vaccination, however, Xia et al. reported that the incidence of overall AEFI was <35% with the use of BBIBP-CorV vaccine. Finally, a study by Khobragade et al. shows the occurrence of overall AEFI in the ZyCoV-D (DNA vaccine) groups was 3.13% after the first dose, which was no different compared with the placebo group (1.44%).
The Texas Children's Hospital Center for Vaccine Development at Baylor College of Medicine has maintained a recombinant protein coronavirus vaccine program for SARS-CoV and MERS coronavirus since 2011. At the beginning of 2020, the program pivoted to developing a recombinant protein COVID-19 vaccine candidate produced in yeast (Pichia pastoris). It was through genetic modification, a more stable and better-controlled vaccine candidate was developed., The yeast-expressed protein was shown to induce high levels of binding and virus-neutralizing antibodies in mice and was protective in a rhesus macaque challenge model. On March 16, GoI gave emergency use authorization for Corbevax to be given for children of 12–14 years. Trials have indicated that Corbevax may cause common postvaccine effects such as mild fever, dizziness, pain in the injection area, fatigue, mild headache, and body ache. However, there is a dearth of literature providing the side effect profile of Corbevax in the real-world/community. Hence, the present study was conducted to assess the incidence and types of AEFI of Corbevax vaccine in children between 12 and 14 years of age.
| Materials and Methods|| |
The present study was a longitudinal descriptive study conducted among children between 12 and 14 years of age who had received Corbevax vaccine at a tertiary care center in western Maharashtra. According to WHO, AEFI is defined as “Any untoward medical occurrence which follows immunization and which does not necessarily have a causal relationship with the usage of the vaccine. If not rapidly and effectively dealt with, can undermine confidence in a vaccine and ultimately have dramatic consequences for immunization coverage and disease incidence”. The study was conducted from March 16 to May 31, 2022. A standardized questionnaire was prepared to collect data on the side effects. The questionnaire consisted of both close-ended and open-ended questions. The questionnaire was circulated among epidemiologists, public health experts, and pediatricians for content validity. The training session was conducted for persons administering the questionnaire. The parents of the participants were asked telephonically about the onset of symptoms at 24 h, 72 h and were followed up for 7 days after the first dose and second doses of vaccinations. The study was approved by the institutional ethical committee of the institute. All the parents of the children were informed at the time of the vaccine regarding the study, and informed consent was taken at the time of vaccine administration. The children who reported side effects were counseled, and appropriate management was administered. The data were collected in an Excel spreadsheet, and data were analyzed using an electronic statistical package IBM SPSS for Windows, version 20.0. Armonk, NY, USA: IBM Corp. P < 0.05 was considered statistically significant.
| Results|| |
A total of 358 children of age 12–14 years received Corbevax vaccine at our tertiary care center in western Maharashtra. The majority of children were males 190 (52.1%) and were of 13–14 years of age (89.1%), detailed demographic profile is depicted in [Table 1]. Almost 80% of vaccines developed mild adverse after vaccination; however, no serious AEFI was reported. Fifty-five (17%) participants among 303 had multiple AEFIs after the first dose and 67 (21%) participants among 320 participants had multiple AEFIs after the second dose. The most common adverse effects were pain in the abdomen, followed by headache and pain at the site of injection [Figure 1]. It was observed that local side effects such as pain at the injection site were less commonly reported after the second dose than after the first dose of Corbevax vaccine. Overall, reactogenicity was higher after the second dose with more individuals reporting systemic side effects such as chills, headache/body ache, and pain in the abdomen as compared to more local reactions after the first dose.
|Table 1: Distribution of adverse event following immunisation as per dose and basic demographic characteristics|
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|Figure 1: AEFI after Corbevax vaccination (n = 358), AEFI: Adverse Events Following Immunization|
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To identify risk factors for AEFI after the second dose of Corbevax, factors such as age, sex, and AEFI after the first dose of vaccination were analyzed using univariate and multivariate analysis. Only occurrence of AEFI after first dose (odds ratio: 158.87, 95% confidence interval [CI] 46.58–528.28, P < 0.005) emerged as an independent risk factor for development of AEFI after second dose [Table 2]. Thus, indicating that children who had developed AEFI after the first dose of Corbevax were at a higher risk of developing AEFI after the second dose as compared to children who did not have AEFI after the first dose of Corbevax vaccine.
|Table 2: Univariate and multivariate analysis of predictive factors for adverse event following immunization after the second dose|
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| Discussion|| |
Since the development of vaccines against COVID-19, there have been concerns of AEFI because for the first time in history, the COVID vaccines have been developed in a very short duration and used in masses under emergency use authorization. Many adverse events are not reported in the clinical trials due to their smaller sample size and lower frequency of AEFIs in ideal trial settings; however, more AEFIs are likely to emerge when vaccines are used in masses in community settings. Therefore, postvaccination adverse reactions monitoring is important to establish the safety and efficacy of the vaccines as well as to provide real-life data to policymakers to ensure judicious and evidence-based public health decisions are made for the betterment of the population
As per WHO's safety surveillance module manual for COVID-19 vaccines, “COVID-19 vaccination surveillance systems need to be prepared for identifying and responding to both AEFIs and AESIs.” Hence, in the present study, we followed up with the vaccine beneficiaries (children between 12 and 14 years of age who had received Corbevax vaccine at our tertiary care center in western Maharashtra) for AEFI at 24 h, 72 h, and 7 days both after the first dose and second dose of Corbevax vaccine.
We found that the most commonly reported AEFIs after the first dose of the Corbevax vaccine were pain/tenderness at the injection site, headache, and pain in the abdomen. In an immunogenic superiority and safety study of Biological E's CORBEVAX™ vaccine which was compared to COVISHIELD™ vaccine in phase III, single-blind, multicenter, randomized clinical trial by Thuluva et al., the most common AEFI reported by study subjects were injection site pain (17·8%), pyrexia (12·3%), myalgia (10·4%), headache (7·7%), and fatigue (7·3%). Most of the adverse reactions were mild to moderate in severity. Compared to this report, a higher percentage of mild AEFIs was observed in our study. Similar to our study, in one of the media reports of Hindustan Times dt June 11, 2022, there were no serious AEFI cases reported from 28000 Corbevax beneficiaries in Pune.
In our study, 320 (89%) of individuals developed AEFI after the second dose, as on date, even after a rigorous literature search, we were unable to find studies reporting the incidence of AEFI after the second dose of Corbevax, however, similar high incidence of AEFI have been reported after the second dose of ChAdOx1 (86%) and BNT162 (92%). Similarly, a large longitudinal descriptive study conducted among 2529 vaccine beneficiaries in western Maharashtra found that only 14% of individuals did not suffer any AEFI after the first/second dose. Local side effect such as pain at the injection site was more common after the first dose, and systemic side effects were more common after the second dose of Corbevax in our study participants. Similar, less local effects have been less commonly reported after the second dose than after the first dose of BNT162b2 vaccine. However, in contrast, systemic side effects have been reported more commonly after the first dose than after the second dose of ChAdOx1 vaccine. Multivariate analysis found that the occurrence of AEFI after the first dose of Corbevax vaccine (odds ratio: 158.87, 95% CI 46.58–528.28, P < 0.005) as an independent risk factor for the development of AEFI after the second dose. Number of studies has reported that previously COIVD immunized (one dose)/past SARS-CoV-2 infection-positive individuals have higher chances of AEFI. Thus, although it remains to be confirmed, it is possible that increased reactogenicity is due to increased immunogenicity. Studies have shown that previous exposure to the COVID vaccine/past infection increases immunogenicity as these individuals have higher antibody titers as compared to naïve individuals.,
| Conclusion|| |
At present, the global focus is primarily toward the prevention of COVID-19, hence most of the publications relate to the efficacy of vaccines. Corbevax was introduced in India in March 2022 for children between 12 and 14 years, but to the best of our knowledge, till date, there is no study specifically focused of AEFI due to Corbevax in children in the targeted age group. Our study focuses specifically on AEFI due Corbevax in children (between 12 and 14 years) and the finding indicates that Corbevax is a safe vaccine with few mild side effects, thus reinforcing the faith in the safety profile of the vaccine.
Financial support and sponsorship
Any grants/equipment/drugs, and/or other support that facilitated the conduct of research/writing of the manuscript (Including AFMRC project details, if applicable).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Frenck RW Jr., Klein NP, Kitchin N, Gurtman A, Absalon J, Lockhart S, et al.
Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N Engl J Med 2021;385:239-50.
Ali K, Berman G, Zhou H, Deng W, Faughnan V, Coronado-Voges M, Ding B, Dooley J, Girard B, Hillebrand W, Pajon R, Miller JM, Leav B, McPhee R. Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents. N Engl J Med. 2021;385:2241-2251. doi: 10.1056/NEJMoa2109522. Epub 2021. PMID: 34379915; PMCID: PMC8385554.
Han B, Song Y, Li C, Yang W, Ma Q, Jiang Z, et al.
Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: A double-blind, randomised, controlled, phase 1/2 clinical trial. Lancet Infect Dis 2021;21:1645-53.
Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al.
Safety and immunogenicity of an inactivated COVID-19 vaccine, BBIBP-CorV, in people younger than 18 years: A randomised, double-blind, controlled, phase 1/2 trial. Lancet Infect Dis 2022;22:196-208.
Khobragade A, Bhate S, Ramaiah V, Deshpande S, Giri K, Phophle H, et al.
Efficacy, safety, and immunogenicity of the DNA SARS-CoV-2 vaccine (ZyCoV-D): The interim efficacy results of a phase 3, randomised, double-blind, placebo-controlled study in India. Lancet 2022;399:1313-21.
Chen WH, Wei J, Kundu RT, Adhikari R, Liu Z, Lee J, et al.
Genetic modification to design a stable yeast-expressed recombinant SARS-CoV-2 receptor binding domain as a COVID-19 vaccine candidate. Biochim Biophys Acta Gen Subj 2021;1865:129893.
India's Corbevax Vaccine Was Developed at Texas Children's Hospital. Archive.ph. 2022. Available from: https://archive.ph/3GoF0
. [Last accessed on 2022 Jun 07].
Pollet J, Chen WH, Versteeg L, Keegan B, Zhan B, Wei J, et al.
SARSCoV-2 RBD219-N1C1: A yeast-expressed SARS-CoV-2 recombinant receptor-binding domain candidate vaccine stimulates virus neutralizing antibodies and T-cell immunity in mice. Hum Vaccin Immunother 2021;17:2356-66.
Thuluva S, Paradkar V, Gunneri SR, Yerroju V, Mogulla R, Turaga K, et al.
Evaluation of safety and immunogenicity of receptor-binding domain-based COVID-19 vaccine (Corbevax) to select the optimum formulation in open-label, multicentre, and randomised phase-1/2 and phase-2 clinical trials. EBioMedicine 2022;83:104217.
World Health Organization. Covid-19 Vaccines: Safety Surveillance Manual. Geneva: World Health Organization; 2020.
Elgendy MO, El-Gendy AO, Mahmoud S, Mohammed TY, Abdelrahim ME, Sayed AM. Side effects and efficacy of COVID-19 vaccines among the Egyptian population. Vaccines (Basel) 2022;10:109.
Bobdey S, Sahu R, Yadav AK, Kaushik S K, Sreekanth K S, Nagari N, Koundinya K. A longitudinal study to estimate adverse events following two doses of COVID-19 vaccination. Med J DY Patil Vidyapeeth 2022;15, Suppl S2:334-8.
Menni C, Klaser K, May A, Polidori L, Capdevila J, Louca P, et al.
Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID symptom study app in the UK: A prospective observational study. Lancet Infect Dis 2021;21:939-49.
Krammer F, Srivastava K, Alshammary H, Amoako AA, Awawda MH, Beach KF, et al
. Antibody Responses in Seropositive Persons after a Single Dose of SARS-CoV-2 mRNA Vaccine. N Engl J Med. 2021;384:1372-4. doi: 10.1056/NEJMc2101667. Epub 2021. PMID: 33691060; PMCID: PMC8008743
Wise J. Covid-19: People who have had infection might only need one dose of mRNA vaccine. BMJ 2021;372:n308.
[Table 1], [Table 2]