Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections
Sivan Gazit, Roei Shlezinger, Galit Perez, Roni Lotan, Asaf Peretz, Amir Ben-Tov, Dani Cohen, Khitam Muhsen, Gabriel Chodick, Tal Patalon
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Background: Reports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear. Methods: We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naive individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel.
Results: SARS-CoV-2-naive vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naive vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naive vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected.
Conclusions: This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.