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Review 1: "Necessity of COVID-19 vaccination in previously infected individuals"

Reviewer: Murat Akova, Mine Durusu Tanriover (Hacettepe University Hospitals) | 📗📗📗📗◻️

Published onMar 15, 2022
Review 1: "Necessity of COVID-19 vaccination in previously infected individuals"
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key-enterThis Pub is a Review of
Necessity of COVID-19 vaccination in previously infected individuals

ABSTRACTBackgroundThe purpose of this study was to evaluate the necessity of COVID-19 vaccination in persons previously infected with SARS-CoV-2.MethodsEmployees of the Cleveland Clinic Health System working in Ohio on Dec 16, 2020, the day COVID-19 vaccination was started, were included. Any subject who tested positive for SARS-CoV-2 at least 42 days earlier was considered previously infected. One was considered vaccinated 14 days after receipt of the second dose of a SARS-CoV-2 mRNA vaccine. The cumulative incidence of SARS-CoV-2 infection over the next five months, among previously infected subjects who received the vaccine, was compared with those of previously infected subjects who remained unvaccinated, previously uninfected subjects who received the vaccine, and previously uninfected subjects who remained unvaccinated.ResultsAmong the 52238 included employees, 1359 (53%) of 2579 previously infected subjects remained unvaccinated, compared with 20804 (42%) of 49659 not previously infected. The cumulative incidence of SARS-CoV-2 infection remained almost zero among previously infected unvaccinated subjects, previously infected subjects who were vaccinated, and previously uninfected subjects who were vaccinated, compared with a steady increase in cumulative incidence among previously uninfected subjects who remained unvaccinated. Not one of the 1359 previously infected subjects who remained unvaccinated had a SARS-CoV-2 infection over the duration of the study. In a Cox proportional hazards regression model, after adjusting for the phase of the epidemic, vaccination was associated with a significantly lower risk of SARS-CoV-2 infection among those not previously infected (HR 0.031, 95% CI 0.015 to 0.061) but not among those previously infected (HR 0.313, 95% CI 0 to Infinity).ConclusionsIndividuals who have had SARS-CoV-2 infection are unlikely to benefit from COVID-19 vaccination, and vaccines can be safely prioritized to those who have not been infected before.SummaryCumulative incidence of COVID-19 was examined among 52238 employees in an American healthcare system. COVID-19 did not occur in anyone over the five months of the study among 2579 individuals previously infected with COVID-19, including 1359 who did not take the vaccine.

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.



The real-life retrospective study by Shrestha and colleagues analyses the cumulative incidence of COVID-19 among a large cohort of healthcare workers comparing those who were either infected or not infected and either vaccinated or not vaccinated. The study aimed to demonstrate whether people who were previously infected with SARS-CoV-2 and then vaccinated have a lower incidence of COVID-19 compared to those previously infected people who did not receive the vaccine. Available data show that the immunity conferred by the infection can be long-lasting, but the recommendations on vaccination of individuals who already contracted COVID19 are variable. The hypothesis that previously infected people do not have an increased risk for infection if they remain unvaccinated would help prioritize people to whom the vaccines would be applied. In a world where vaccine inequity and shortages are very much pronounced, the results proving this hypothesis would be valuable as they will prioritize available vaccines to people who will benefit from them more. The authors retrospectively analyzed the data of a cohort of over 50 thousand healthcare workers. Ethical approval was obtained to use and process the data. As the cohort was composed of active health system employees, data retrieved from the occupational health database on vaccination and COVID-19 testing and diagnosis were precise and complete. The study population is diverse in the face of a health system. All of those who were employed at the time of vaccine roll-out were included regardless of their background and epidemiological characteristics. The study results contribute to decision-making processes as not even a single COVID-19 case occurred among the people who contracted the infection regardless of the vaccination status. The study's strengths are the large sample size, the real-life design, and the relatively long follow-up period compared to phase 3 studies. The study's limitations are the lack of children and minor representation of elderly and immunosuppressed subjects, if any, in the cohort, which precludes the generalizability of the results to a wider and more heterogeneous population. The authors discussed their findings in the light of the available scientific literature and emphasized, especially on the limitations of the study. The conclusion of this study can have a real impact on the policy-making processes and COVID-19 vaccination program implementation of the communities.

Specific Comments:

The study's name could be modified as it is perceived as ‘COVID-19 vaccination is necessary for previously infected individuals.

-A statistical review would be valuable to assess whether the statistical methods were used accurately or not.

-The study's primary outcome is ‘the cumulative incidence of COVID-19 cases’, not the ‘time to SARS-CoV-2 infection’.

- The rationale of the time period chosen as 42 days before the vaccine rollout date should be better explained and justified. Additionally, ‘time to SARS-CoV-2 infection’ was assessed as the study outcome; however, we think that the primary outcome assessed was ‘the cumulative incidence of SARS-CoV-2 in the predefined study period’ outcome was analyzed among groups to test the hypothesis.

-The manuscript confirms previous work that concludes that people who contracted COVID-19 have a very low risk of reinfection and refutes the suggestion that they should receive the vaccine. The results of this study should be verified in other cohorts and in other time periods to see whether these results are generalizable in more vulnerable populations or where the variants of concerns circulate at a higher incidence.

miley cricus:

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mike dawson:

The reviewer rates the study on COVID-19 incidence among healthcare workers as "Reliable" on the RR:C19 Evidence Scale. They commend the study's large cohort size, real-life design, and extensive follow-up period, emphasizing its potential impact on policy-making and vaccination programs. The limitations, such as the absence of children and a limited representation of elderly and immunosuppressed subjects, are acknowledged. Specific comments suggest modifying the study's name, conducting a statistical review, clarifying the rationale for the chosen time period, and distinguishing the primary outcome as the cumulative incidence of COVID-19 cases rather than the time to SARS-CoV-2 infection. The reviewer notes the study's potential significance in prioritizing vaccine distribution amid global shortages and vaccine inequity. Stick Merge