SARS-CoV-2 Reinfection With and Without mRNA Vaccine

Quick Takes

  • Among Israeli residents with prior SARS-CoV-2 infection, single-dose BNT162b2 (Pfizer-BioNTech) mRNA-based vaccine was associated with significantly reduced risk of reinfection (HR, 0.18) and symptomatic reinfection (HR, 0.24).
  • Delta-variant SARS-CoV-2 accounted for the vast majority of reinfections in this cohort, and further research is needed to understand the impact of vaccination on reinfection with Omicron.

Study Questions:

In persons with naturally acquired immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), what is the risk of reinfection following single-dose BNT162b2 (Pfizer-BioNTech) messenger RNA (mRNA)-based vaccine, as compared with no vaccination?


This retrospective observational study was based on data from Maccabi Healthcare Services (MHS), Israel’s second largest health maintenance organization. During the study period of March 2020–December 2021, SARS-CoV-2 variants of concern in Israel were Alpha and Delta (not Omicron), with Delta accounting for the vast majority of reinfections. Per Israeli Ministry of Health guidelines, in March 2021, persons previously infected with SARS-CoV-2 became eligible to receive a single dose of BNT162b2 mRNA vaccine, a minimum of 90 days after infection. The authors simulated a randomized controlled trial by designing a series of multiple nested trials, enrolling convalescent patients as they became eligible for vaccination and matching vaccinated and unvaccinated patients based on age, sex, socioeconomic status, and comorbidities. Outcomes of interest were SARS-CoV-2 reinfection, symptomatic reinfection, and related hospitalizations. The follow-up period was March–December 2021.


A total of 41 trials were emulated, and 107,413 MHS members aged ≥16 years were eligible for ≥1 trial. During the follow-up period, 1,374 patients had a positive SARS-CoV-2 polymerase chain reaction (PCR) result, 874 patients had symptomatic reinfection, and 10 were hospitalized for coronavirus disease 2019 (COVID-19) (including two vaccinated patients). No COVID-19–related deaths occurred. More vaccinated patients than unvaccinated patients had comorbidities such as hypertension (12.5% vs. 8.6%) and diabetes (6.7% vs. 4.8%). Vaccination was associated with significantly decreased risks of reinfection (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.15-0.20) and symptomatic reinfection (HR, 0.24; 95% CI, 0.20-0.29).


Among persons previously infected with SARS-CoV-2, mRNA-based vaccination was associated with decreased risks of reinfection and symptomatic reinfection, as compared with no vaccination.


This study clearly demonstrates that vaccination is protective against Delta-variant SARS-CoV-2 reinfection. Very few patients in this cohort required hospitalization for COVID-19, so it is difficult to know the magnitude of protection that vaccination provided against severe disease. Notably, the prevalence of obesity in the US population is >40%, as compared with <25% in this Israeli cohort. Since obesity is a major risk factor for severe COVID-19, the benefits of vaccination in previously infected US residents are likely even greater than these data suggest. However, given that Omicron is now the dominant SARS-CoV-2 variant, these findings should be extrapolated to the current state with a degree of caution.

Keywords: Adaptive Immunity, COVID-19, COVID-19 Testing, COVID-19 Vaccines, Diabetes Mellitus, Hypertension, Metabolic Syndrome, Obesity, Polymerase Chain Reaction, Primary Prevention, Reinfection, Risk Factors, RNA, Messenger, SARS-CoV-2, Vaccination

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