In a recent study published in the latest issue of The New England Journal of Medicine, researchers conducted a retrospective cohort study in Israel to assess the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection in patients who had recovered from coronavirus disease 2019 (COVID-19).
Vaccine hesitancy might have stemmed from personal safety concerns in patients who wanted reassurance that the COVID-19 vaccine is safe and beneficial. Moreover, the data evidence of vaccine efficacy in patients who had recovered from COVID-19 is still limited. Although current guidelines recommend vaccination for everyone, including those previously infected, it is crucial to assess how long protective immunity lasts.
In Israel, although taking a COVID-19 vaccine is a personal choice, the Israel Ministry of Health issues the Green Pass, an immunity passport, from October 2021 onwards, only to those who get immunized within six months after recovering from COVID-19.
About the study
The researchers reviewed data from electronic medical records of members of Clalit Health Services, Israel, which has the health data of ~52% of the population to assess reinfection rates in patients who had recovered from SARS-CoV-2 infection in not less than 100 days before receiving any COVID-19 vaccine.
They compared the rate of recurrent infection between patients vaccinated with the BNT162b2 vaccine and unvaccinated patients; identified reinfection by the date of the SARS-CoV-2-positive quantitative reverse-transcriptase–polymerase-chain-reaction (RT-qPCR) test at least 100 days after the primary infection. As per the Israeli Ministry of Health, the 100-day cutoff allows recovered patients to receive their COVID-19 vaccination after the recommended time lag of three months post-primary infection. Additionally, they estimated the association between vaccination and reinfection after adjustment for demographic factors and other time-varying covariates using the Cox proportional-hazards regression model.
In a secondary analysis, they assessed vaccine effectiveness, estimated as one minus the hazard ratio (HR), among patients who had received one and two doses of vaccine. All the eligible study subjects were between 16 and 110 years, had contracted primary SARS-CoV-2 infection between August 23, 2020, and May 31, 2021, identified by the date of the first SARS-CoV-2-positive RT-qPCR.
During the study period, the population of vaccinated and unvaccinated groups was dynamic. Up to seven days after receiving the first vaccine dose, participants remained in the unvaccinated group; later, they moved into the vaccinated group. Two previous studies, one a large observational study regarding the BNT162b2 booster dose and another a randomized, controlled trial of the BNT162b2 vaccine, have validated that the 7-day time lag is ideal for the analysis of vaccine efficacy.
Study findings
Among the vaccinated patients, those in the age group of 16 and 64 years and over 65 years had the adjusted HR for reinfection of 0.18 and 0.40, respectively; subsequently, the observed vaccine effectiveness among patients of these two age groups was 82% and 60%, respectively.
Although the vaccine effectiveness was lower among patients over 65 years than the younger patients, vaccination still offered substantial immune protection. Contrastingly, the reinfection rate among the older patients was much lower, with only 3.02 cases per 100,000 persons per day versus 10.79 cases per 100,000 persons per day among the younger patients.
The adjusted HR for reinfection among the patients who had received one vaccine dose and two doses was 0.98, suggesting that two vaccine doses offered no additional protection than one vaccine dose to previously infected SARS-CoV-2 patients. It is worth noting here that only 19% of the vaccinated patients received more than one vaccine dose during the study period; however, prior SARS-CoV-2 exposure combined with the one vaccine dose helped them mount a more robust and persistent immunogenic response.
Conclusions
The study observations showed that among patients who had recovered from COVID-19, one dose of the BNT162b2 vaccine reduced the risk of recurrent infection by 60%-82% across all age groups. Moreover, the second dose of vaccine offered no additional benefit against reinfection compared with one vaccine dose.
More importantly, the data evidence gathered in this study supports a public health policy of mandating vaccination of patients who have recovered from COVID-19 in Israel.
Journal reference:
- Ariel Hammerman, Ruslan Sergienko, Michael Friger, Tanya Beckenstein, Alon Peretz, Doron Netzer, Shlomit Yaron, and Ronen Arbel. (2022). Effectiveness of the BNT162b2 Vaccine after Recovery from Covid-19. New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2119497