Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Naturally Acquired Immunity versus Vaccine-induced Immunity, Reinfections versus Breakthrough Infections: A Retrospective Cohort Study

Background Waning of protection against infection with SARS-CoV-2 conferred by 2 doses of the BNT162b2 vaccine begins shortly after inoculation and becomes substantial within four months. With that, the impact of prior infection on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined the long-term protection of naturally acquired immunity (protection conferred by previous infection) compared to vaccine-induced immunity. Methods A retrospective observational study of 124,500 persons, compared two groups: (1) SARS-CoV-2-naïve individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, and (2) previously infected individuals who have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes - infection, symptomatic disease (COVID-19), hospitalization and death – between June 1 to August 14, 2021, when the Delta variant was dominant in Israel. Results SARS-CoV-2-naïve vaccinees had a 13.06-fold (95% CI, 8.08-21.11) increased risk for breakthrough infection with the Delta variant compared to unvaccinated-previously-infected individuals, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time between March 2020 to February 2021, evidence of waning naturally acquired immunity was demonstrated, though SARS-CoV-2 naïve vaccinees still had a 5.96-fold (95% CI, 4.85-7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51-9.21) increased risk for symptomatic disease. Conclusions Naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity.