Individuals with recent prior SARS-CoV-2 infection are at reduced risk of Omicron infection and associated hospitalization

Omicron sub-lineages such as BA2.12.1 and BA5 have breached prior infection-induced immunity and vaccine-induced immunity. This capacity of Omicron to reinfect patients calls for a characterization of vaccination, infection, and reinfection patterns. We analyzed de-identified longitudinal electronic health records for 389,746 individuals (88,679 fully-vaccinated, 184,205 boosted, 73,184 with prior infection) across multiple US states. Compared to individuals with only full vaccination, the rates of SARS-CoV-2 infections in the Omicron era were reduced for individuals with additional prior infection (1.4 to 1.8-fold reduced, depending on vaccine status) or booster vaccination (1.3 to 2.0-fold reduced). Although prior infection was associated with lower incidence of SARS-CoV-2 infection, we found that the relative risk (RR) of infections for individuals with prior infection has increased during Omicron. During October, 2021, RR was 0.11 [0.10-0.13, 95% CI] while during May, 2022, it increased to 0.57 [0.46-0.68, 95% CI], suggesting an increase in reinfections with Omicron. Furthermore, we found that time since prior infection is associated with risk of reinfection, providing evidence of waning immunity. Prior infections before June, 2021, were associated with marginal reduction in risk of infection (eg., RR = 0.80 [0.68-0.90] for prior infection during January, 2021), while recent prior infections were associated with significant reduction in risk (eg., RR = 0.24 [0.20-0.29, 95% CI] for prior infection during November, 2021). Despite an observed increase in reinfections and vaccine breakthrough infections, our findings emphasize the protective effect of natural and vaccine immunity, with prior infection providing [~]6 months of protection from reinfection.