Immunity to SARS-CoV-2 is building up globally, but will this be sufficient to prevent future COVID-19 epidemics in the face of variants and waning immunity? Manaus, Brazil offers a concerning glimpse of what may come: six months after the majority of the citys population experienced primary infection, a second wave with a new strain resulted in more deaths than the first wave. Current hypotheses for this surge rely on prior immunity waning due to time and antigenic distance. Here we show this hypothesis predicts a severe endemic state. We propose an alternative hypothesis in which individuals infected in the first wave lose protection against transmission but retain immunity against severe disease and show this hypothesis is equally compatible with existing data. In this scenario, the increased number of deaths is due to an increased infection fatality ratio (IFR) for primary infections with the new variant. This alternative predicts a mild endemic state will be reached within decades. Collecting data on the severity of reinfections and infections post-vaccination as a function of time and antigenic distance from the original exposure is crucial for optimizing control strategies.
Severity of SARS-CoV-2 reinfections in second wave determines likelihood of mild endemicity