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After initially containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many European and Asian countries had a resurgence of COVID-19 consistent with a large proportion of the population remaining susceptible to the virus after the first epidemic wave. By contrast, in Manaus, Brazil, a study of blood donors indicated that 76% (95% CI 67–98) of the population had been infected with SARS-CoV-2 by October, 2020. High attack rates of SARS-CoV-2 were also estimated in population-based samples from other locations in the Amazon Basin—eg, Iquitos, Peru 70% (67–73). The estimated SARS-CoV-2 attack rate in Manaus would be above the theoretical herd immunity threshold (67%), given a basic case reproduction number (R0) of 3. In this context, the abrupt increase in the number of COVID-19 hospital admissions in Manaus during January, 2021 (3431 in Jan 1–19, 2021, vs 552 in Dec 1–19, 2020) is unexpected and of concern (figure). After a large epidemic that peaked in late April, 2020, COVID-19 hospitalisations in Manaus remained stable and fairly low for 7 months from May to November, despite the relaxation of COVID-19 control measures during that period (figure). There are at least four non-mutually exclusive possible explanations for the resurgence of COVID-19 in Manaus. First, the SARS-CoV-2 attack rate could have been overestimated during the first wave, and the population remained below the herd immunity threshold until the beginning of December, 2020. In this scenario, the resurgence could be explained by greater mixing of infected and susceptible individuals during December. The 76% estimate of past infection might have been biased upwards due to adjustments to the observed 52·5% (95% CI 47·6–57·5) seroprevalence in June, 2020, to account for antibody waning. However, even this lower bound should confer important popula tion immunity to avoid a larger outbreak. 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TL;DRAfter initially containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many European and Asian countries had a resurgence of COVID-19 consistent with a large proportion of the population remaining susceptible to the virus after the first epidemic wave, while in Manaus, Brazil, a study of blood donors indicated that 76% of thepopulation had been infected with SARS- covirus 2 by October, 2020. (Semantic Scholar)