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Review 1: "Effectiveness of CoronaVac in the setting of high SARS-CoV-2 P.1 variant transmission in Brazil: A test-negative case-control study"

Reviewer: Feng-Cai Zhu (Jiangsu Province CDC) | 📗📗📗📗◻️

Published onMay 07, 2022
Review 1: "Effectiveness of CoronaVac in the setting of high SARS-CoV-2 P.1 variant transmission in Brazil: A test-negative case-control study"
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key-enterThis Pub is a Review of
Effectiveness of CoronaVac among healthcare workers in the setting of high SARS-CoV-2 Gamma variant transmission in Manaus, Brazil: A test-negative case-control study
Description

AbstractBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported.MethodsWe performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection.FindingsFor the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case- control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate.InterpretationEvidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented.FundingFundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of ManausResearch in ContextEvidence before this studyWe searched PubMed for articles published from inception of the pandemic until April 3, 2021, with no language restrictions, using the search terms “P.1” AND “vaccine” AND “SARS-CoV-2”. Additionally, we searched for “CoronaVac” AND “SARS-CoV-2”. Early studies have found plasma from convalescent COVID-19 patients and sera from vaccinated individuals have reduced neutralisation of the SARS-CoV-2 variant, Gamma or P.1, compared with strains isolated earlier in the pandemic. Pfizer BNT162b2 mRNA, Oxford-AstraZeneca ChAdOx1, and CoronaVac are the only vaccines for which such data has been published to date.No studies reported effectiveness of any vaccine on reducing the risk of infection or disease among individuals exposed to P.1 or in settings of high P.1 transmission.Added value of this studyThis study finds that vaccination with CoronaVac was 49.4% (95% CI 13.2 to 71.9) effective at preventing COVID-19 in a setting with likely high prevalence of the Gamma Variant of Concern. However, an analysis of effectiveness by dose was underpowered and failed to find significant effectiveness of the two-dose schedule of CoronaVac (estimated VE 37.1%, 95% CI -53.3 to 74.2).Implications of all the available evidenceThese findings are suggestive for the effectiveness of CoronaVac in healthcare workers in the setting of widespread P.1 transmission but must be strengthened by observational studies in other settings and populations. Based on this evidence, there is a need to implement sustained non-pharmaceutical interventions even as vaccination campaigns continue.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review:

This article is aimed to estimate the effectiveness of the CoronaVac COVID-19 vaccine in a setting of SARS-CoV-2 P.1 variant transmission. The second epidemic of COVID-19 in Brazil was associated with the emergence and spread of P.1. The author chose Manaus as the study site, where P.1 accounted for 75% of genotyped SARS-CoV-2 samples at the peak of its epidemic. 

The author conducted a retrospective, test-negative, matched case-control study to estimate the effectiveness of CoronaVac in reducing the odds of primary and secondary outcomes of, respectively, symptomatic and all RT-PCR-confirmed SARS-CoV-2 infections. 393 and 418 case-control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. In the earlier analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period of 14 days or more after receiving the first dose. However, they estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after the first vaccination (aOR 2.11, 95% CI 1.36-3.27) suggests that among this population of healthcare workers, those at higher risk might take up vaccine earlier, leading to underestimation of its effectiveness. 

Data suggests that the Coronavac vaccine is effective in areas where P.1 mutants are prevalent, and the effectiveness may be underestimated. So the main study aims are generally justified by its methods and data.    

First, in the introduction section, the author miswrote the date of the emergence of the mutant P.1, which should be November 2020.

Second, in the results section, in the last sentence of the paragraph “Early At Least One-Dose Analysis” and “Two-Dose Analysis,” the data in supplementary form 5 were mentioned. Still, the actual supplementary form did not contain such data. Please check it. In addition, the data for “Female sex (AOR 0.50, 95%CI 0.38 to 0.81)” mentioned in the paragraph “Early at-least-one-dose analysis” is also inconsistent with the table. The table shows “Female sex (AOR 0.55, 95%CI 0.38 to 0.81).” 

The amount of data is relatively large. Therefore, please check the results carefully to ensure the authenticity and accuracy of the data.

Evidence and arguments are presented to support the advancement of COVID-19 understanding within society. In addition, to better understand the challenges to epidemic prevention and control by the emergence of coronavirus mutants such as P.1.

This paper proposes the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented. Provide theoretical guarantees for the policy of vaccination. I recommend this manuscript for publishing.

It is well structured and well written, with an ability to speak to key audiences. Figure 2. The flowchart for Case and Control Selection can be modified. The existing Flowchart only provides the case and control groups of two injection doses.

In this paper, the authors pay attention to ethics, control bias from various aspects, analyze the possibility of bias, and reduce bias by pairing. In addition, the accuracy and comprehensiveness of the information sources are ensured as far as possible by collecting the information of medical personnel.

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