Risk and severity of SARS-CoV-2 reinfections during 2020-2022 in Vojvodina, Serbia: a population-level study

Background: Data on the rate and severity of reinfections with SARS-CoV-2 in real-world settings are scarce and the effects of booster vaccination on reinfection risk are unknown. Methods: In a retrospective cohort study, all SARS-CoV-2 laboratory-confirmed residents of Vojvodina, registered in the database of the Institute of Public Health of Vojvodina, between March 6, 2020 and October 31, 2021, were followed for reinfection >90 days after primary infection. Data were censored at the end of follow-up (January 31, 2022) or death. The risk of reinfection was visualized with Kaplan-Meier plots. To examine whether vaccination protected from reinfection, the subset of Vojvodina residents with primary infection in 2020 (March 6-December 31) were matched (1:2) with controls without reinfection. Results: Until January 31, 2022, 13,792 reinfections were recorded among 251,104 COVID-19 primary infections (5.49%). Most reinfections (86.8%) were recorded in January 2022. Reinfections were mostly mild (99.2%). Hospitalizations were uncommon (1.08% vs. 3.70% in primary infection) and COVID-19 deaths were very rare (n=20, case fatality rate 0.15%). The overall incidence rate of SARS-CoV-2 reinfections was 5.99 (95% CI 5.89-6.09) per 1,000 person-months for those who survived the first three months after primary infection. The reinfection risk was estimated as 0.76% at six months, 1.36% at nine months, 4.96% at 12 months, 16.7% at 15 months, and 18.9% at 18 months. Among 34 second reinfections, none resulted in hospitalization or death. Unvaccinated (OR=1.23; 95%CI=1.14-1.33), incompletely (OR=1.33; 95%CI=1.08-1.64) or completely vaccinated (OR=1.50; 95%CI=1.37-1.63), were modestly more likely to be reinfected compared with those who received a third (booster) vaccine dose. Conclusions: SARS-CoV-2 reinfections were exceptionally uncommon until the end of 2021 but became common with the advent of the Omicron variant. Very few reinfections were severe. A vaccination booster dose may modestly reduce reinfection risk.