Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa

Abstract

Objective: To examine whether SARS-CoV-2 reinfection risk has changed through time in South Africa, in the context of the emergence of the Beta, Delta, and Omicron variants Design: Retrospective analysis of routine epidemiological surveillance data Setting: Line list data on SARS-CoV-2 with specimen receipt dates between 04 March 2020 and 27 November 2021, collected through South Africa's National Notifiable Medical Conditions Surveillance System Participants 2,796,982 individuals with laboratory-confirmed SARS-CoV-2 who had a positive test result at least 90 days prior to 27 November 2021. Individuals having sequential positive tests at least 90 days apart were considered to have suspected reinfections. Main outcome measures: Incidence of suspected reinfections through time; comparison of reinfection rates to the expectation under a null model (approach 1); empirical estimates of the time-varying hazards of infection and reinfection throughout the epidemic (approach 2) Results: 35,670 suspected reinfections were identified among 2,796,982 individuals with laboratory-confirmed SARS-CoV-2 who had a positive test result at least 90 days prior to 27 November 2021. The number of reinfections observed through the end of the third wave was consistent with the null model of no change in reinfection risk (approach 1). Although increases in the hazard of primary infection were observed following the introduction of both the Beta and Delta variants, no corresponding increase was observed in the reinfection hazard (approach 2). Contrary to expectation, the estimated hazard ratio for reinfection versus primary infection was lower during waves driven by the Beta and Delta variants than for the first wave (relative hazard ratio for wave 2 versus wave 1: 0.75 (CI95: 0.59-0.97); for wave 3 versus wave 1:0.71 (CI95: 0.56-0.92)). In contrast, the recent spread of the Omicron variant has been associated with a decrease in the hazard of primary infection and an increase in reinfection hazard. The estimated hazard ratio for reinfection versus primary infection for the period from 1 November 2021 to 27 November 2021 versus wave 1 was 2.39 (CI95: 1.88-3.11). Conclusion: Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection. In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. This finding has important implications for public health planning, particularly in countries like South Africa with high rates of immunity from prior infection. Urgent questions remain regarding whether Omicron is also able to evade vaccine-induced immunity and the potential implications of reduced immunity to infection on protection against severe disease and death.