LAUSR

Background With the widespread transmission of the Omicron SARS-CoV-2 variant, reinfections have become increasingly common. Here, we explored the role of immunity, primary infection severity, and variant predominance in the risk of reinfection and severe COVID-19 during Omicron predominance in Mexico. Methods We analyzed reinfections in Mexico in individuals with a primary infection separated by at least 90 days from reinfection using a national surveillance registry of SARS-CoV-2 cases from March 3rd, 2020, to August 13th, 2022. Immunity-generating events included primary infection, partial or complete vaccination, and booster vaccines. Reinfections were matched by age and sex with controls with primary SARS-CoV-2 infection and negative RT-PCR or antigen test at least 90 days after primary infection to explore reinfection and severe disease risk factors. We also compared the protective efficacy of heterologous and homologous vaccine boosters against reinfection. Results We detected 231,202 SARS-CoV-2 reinfections in Mexico, most occurring in unvaccinated individuals (41.55%). Over 207,623 reinfections occurred during periods of Omicron (89.8%), BA.1 (36.74%), and BA.5 (33.67%) subvariant predominance and a case-fatality rate of 0.22%. Vaccination protected against reinfection, without significant influence of the order of immunity-generating events and provided >90% protection against severe reinfections. Heterologous booster schedules were associated with ~11% and ~ 54% lower risk for reinfection and reinfection-associated severe COVID-19, respectively, modified by time-elapsed since the last immunity-generating event, when compared against complete primary schedules. Conclusion SARS-CoV-2 reinfections increased during Omicron predominance. Hybrid immunity provides protection against reinfection and associated severe COVID-19, with potential benefit from heterologous booster schedules.