mazonas state reported the first confirmed SARS-CoV-2 case in Manaus, the state capital, in March 2020 in a traveler returning from Europe 1 . By late February 2021, >306,000 laboratory-confirmed cases and more than 10,400 deaths in Amazonas had been reported 2 . The COVID-19 epidemic in Amazonas is, at the time of writing, characterized by two exponentially growing curves of cases (Fig. 1a). Epidemiological data from surveillance of severe acute respiratory illness (SARI) and burials indicate that the first wave of the epidemic started in March 2020 and peaked around early May 2020, when the number of cases dropped and then remained roughly stable from June to November 2020. However, in mid-December the number of cases started to grow exponentially, establishing the second wave of the epidemic.A new SARS-CoV-2 VOC, designated P.1 and also knowns as N501Y.V3, recently emerged in Manaus. Lineage P.1 was first detected in four travelers returning to Japan from Amazonas state on 2 January 2021 (ref. 3 ) and was soon recognized as an emergent lineage in Manaus 4 . The VOC P.1 harbors 21 lineage-defining mutations, including ten in the Spike protein (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, H655Y and T1027I). The emergence of P.1 was touted as one of the putative causes of the second wave of COVID-19 in Manaus 5 . However, the precise relationship between circulating SARS-CoV-2 variants and epidemic dynamics in Amazonas remains unclear due to the paucity of viral sequences sampled in this Brazilian state before December 2020. Results Evidence of successive SARS-CoV-2 lineage replacements in Amazonas.To acquire a more in-depth understanding of the genetic diversity of SARS-CoV-2 variants circulating in Amazonas state since the early epidemic, we generated 250 SARS-CoV-2 high-quality, whole-genome sequences from individuals living in 25 municipalities, between 16 March 2020 and 13 January 2021 (Fig. 1a,b). Viral sequences were generated at FIOCRUZ Amazônia, which is part of both the Amazonas state health genomics network (REGESAM) and the consortium FIOCRUZ COVID-19 Genomics Surveillance Network of the Brazilian Ministry of Health (http:// www.genomahcov.fiocruz.br/). Our genomic survey revealed that most sequences were classified into five lineages:

The Northern Brazilian state of Amazonas is one of the most heavily affected country regions by the COVID-19 epidemic and experienced two exponential growing waves in early and late 2020. Through a genomic epidemiology study based on 250 SARS-CoV-2 genomes from different Amazonas municipalities sampled between March 2020 and January 2021 we revealed that the first exponential growth phase was driven mostly by the dissemination of lineage B.1.195 which was gradually replaced by lineage B.1.1.28. The second wave coincides with the emergence of the variant of concern (VOC) P.1 which evolved from a local B.1.1.28 clade in late November and rapidly replaced the parental lineage in less than two months. Our findings support that successive lineage replacements in Amazonas were driven by a complex combination of variable levels of social distancing measures and the emergence of a more transmissible VOC P.1 virus. These data provide unique insights to understanding the mechanisms that underlie the COVID-19 epidemic waves and the risk of disseminating SARS-CoV-2 VOC P.1 in Brazil and potentially worldwide.

T he effi ciency and persistence of natural protective immunity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination are currently unknown. Reinfection cases have been reported in different countries ( 1), but the differentiation between cases of reinfection and viral persistence remains a challenge. The detection of 2 coronavirus disease (COVID-19) episodes >90 days apart and caused by 2 different lineages of SARS-CoV-2 remains the most reliable evidence of reinfection (2). In this article, we describe a reinfection case and highlight details about the genomic features of the 2 COVID-19 episodes. In addition, we demonstrate that the virus in the second episode was related to the emerging variant of interest (VOI) designated as lineage P.2, which is currently circulating throughout Brazil.

Her research interests include molecular evolution of human pathogens and their epidemiology.

SummaryThe rapid spread of the SARS-CoV-2 Variant of Concern (VOC) Gamma during late 2020 and early 2021 in Brazilian settings with high seroprevalence raised some concern about the potential role of reinfections in driving the epidemic. Very few cases of reinfection associated with the VOC Gamma, however, have been reported. Here we describe 25 cases of SARS-CoV-2 reinfection confirmed by real-time RT-PCR twice within months apart in Brazil. SARS-CoV-2 genomic analysis confirmed that individuals were primo-infected between March and December 2020 with distinct viral lineages, including B.1.1, B.1.1.28, B.1.1.33, B.1.195 and P.2, and then reinfected with the VOC Gamma between 3 to 12 months after primo-infection. The overall mean cycle threshold (Ct) value of the first (25.7) and second (24.5) episodes were roughly similar for the whole group and 14 individuals displayed mean Ct values < 25.0 at reinfection. Sera of 14 patients tested by plaque reduction neutralization test after reinfection displayed detectable neutralizing antibodies against Gamma and other SARS-CoV-2 variants (B.1.33, B.1.1.28 and Delta). All individuals have milder or no symptoms after reinfection and none required hospitalization. The present study demonstrates that the VOC Gamma was associated with reinfections during the second Brazilian epidemic wave in 2021 and raised concern about the potential infectiousness of reinfected subjects. Although individuals here analyzed failed to mount a long-term sterilizing immunity, they developed a high anti-Gamma neutralizing antibody response after reinfection that may provide some protection against severe disease.