Review 1: "A Real World Evaluation of the safety and immunogenicity of the Covishield vaccine, ChAdOx1 nCoV- 19 Corona Virus Vaccine (Recombinant) in Health Care Workers (HCW) in National Capital Region (NCR) of India: A preliminary report"

Feng-Cai Zhu

doi:doi:10.1162/2e3983f5.85935f5b

A Real World Evaluation of the safety and immunogenicity of the Covishield vaccine, ChAdOx1 nCoV- 19 Corona Virus Vaccine (Recombinant) in Health Care Workers (HCW) in National Capital Region (NCR) of India: A preliminary report

by Sushila Kataria, Pooja Sharma, Vikas Deswal, Kuldeep Kumar, Manish Singh, Sazid Alam, Vaibhav Gupta, Padam Singh, Rashmi Phogat, Smita Sarma, Nipun Patil, Rohit Dutt, Renu Saxena, and Naresh Trehan

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dx.doi.org

Description

AbstractBackgroundThe SARS-CoV-2 pandemic has severely impacted health systems, economic and social progress globally in 2020. The rollout of vaccines in several parts of the world is being hailed as a solution to the crisis. With newer and more virulent serotypes on the horizon and limited vaccine available, evaluation of safety and immunogenicity is critical for rationalization of vaccine use in public health.ObjectiveTo evaluate real world safety, and, immunogenicity of the Covishield vaccine, ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) in Health Care Workers (HCW) during the national vaccine roll out in the NCR, New Delhi. The safety is evaluated through Adverse Events and Serious Adverse Events reported though enhanced pharmacovigilance protocols, and, the immunogenicity by quantitative determination of anti-S1 and anti-S2 specific IgG antibodies to SARS-CoV-2 in serum samples collected before the receipt of the vaccine and 14 days after dose 1, using the fully automated LIAISON® SARS-CoV-2 S1/S2 IgG test using the chemiluminescence immunoassay (CLIA)ResultsIn the two weeks after immunization with the Covishield vaccine {ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant)}, none of the 1638 evaluated participants reported any serious adverse events (ie require hospitalization or emergency room visit). Solicited adverse events reported via daily diary cards included pain (62.7%) and soreness (24.1%) at injection site as most common, whereas fever (48.4%), headache (43.4%), myalgia (38.4%), fatigue (33.4%), joint pain (27.0%) and nausea (16.0%) were most common solicited systemic adverse events on day 1. Majority of local and systemic adverse events were seen in first 2 days post vaccination and thereafter they resolved. Lesser reactogenicity was observed in subjects with age >50 years. No major difference was observed in adverse events when subjects were stratified based on history of COVID 19 disease or baseline seropositivity. In our study serostatus improved from 48.2% positive at baseline to 79.0% positive 2 weeks following first dose of vaccination. After first dose of vaccination overall higher percentage (98.2%) of seropositivity rates were observed in those with past history of COVID 19 diseaseConclusionThe Covishield vaccine {ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant)}, was safe and reported mild self limiting adverse events over 2-4 days and had an good early (within 2 weeks) seroresponse. This holds the promise of far reaching impact on vaccine availability for a larger population and thereby providing a widespread coverage.

RR:C19 Evidence Scale rating by reviewer:

Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review:

In countries such as India, where the COVID-19 epidemic has not been effectively controlled, with newer and more virulent serotypes on the horizon and limited vaccines available, the isolation and medical observation of health care personnel associated with COVID-19 will add an additional burden to the medical system, thus the real-world protection rate of COVID-19 vaccine for front-line health care workers is particularly important. In this research, an observational real-world study was developed to evaluate the safety and immunogenicity of ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) in Health Care Workers. Generally speaking, the main study claims made are not strongly justified by its data but may yield some insight, the results and conclusions may resemble those from the hypothetical ideal study, and researchers should consider other theories and evidence to further support it. In addition, the manuscript lacks comparison with previous research and understanding of the current situation, and to a certain extent, it failed to comprehensively investigate the experimental design and put forward specific recommendations.

The safety of ChAdOx1 nCoV-19 Corona Virus Vaccine is evaluated through Adverse Events and Serious Adverse Events reported through enhanced pharmacovigilance protocols. Regarding the widely reported thrombotic events of this vaccine, have they received attention and verification in this study? If there is indeed no thrombosis in the study, is it closely related to the subject’s age, health status, occupation, etc.? Please compare the results of previously announced Covishield vaccine clinical trials and add a discussion.
In this research, the immunogenicity by quantitative determination of anti-S1 and anti-S2 specific IgG antibodies to SARS-CoV-2 in serum samples, using the fully automated LIAISON® SARS-CoV-2 S1/S2 IgG test. Whether the researcher has conducted live virus experiments (especially the Indian variant B.1.617) to verify the neutralizing ability of the antibody, if only the binding ability of the antibody is tested, the research on the immunogenicity of the vaccine is still insufficient. Please add these data and discuss the effectiveness of protection against the currently circulating B.1.617 variants.
Whether this study examined the absolute risk value of SARS-CoV-2 positive after vaccination among health care workers in the real world? is it different from the results of previously published clinical trials? Whether it is related to more frequent nucleic acid testing in health facilities (and thus more asymptomatic infections), a sharp increase in the number of cases during the same period of vaccination, and the average age of health workers are younger than the clinical trial enrolled population and they are at higher risk of exposure? Please supplement and discuss in this study.
Those who had received immunoglobulins and/or convalescent plasma within the three months preceding the planned administration of the vaccine (Jan 16, 2021) were excluded from this research. However, 219 of the 1638 people included in the analysis later have a history of COVID-19 disease, of which 87 were infected in the past 3 months, is there any impact? In table 3, “51.8% baseline seronegative turned seropositive” was stated here, please check this value. Are the data in Table 4 and Graph 1 consistent, and what does the ordinate in Graph 1 represent?