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:

Mayaro Alphavirus is an arbovirus that causes outbreaks of acute febrile illness in the Amazon region of South America. We show here the cases of Mayaro fever that occurred in 2007-2008, in Manaus, a large city and capital of the Amazonas State, in Western Brazilian Amazon. IgM antibodies to Mayaro virus (MAYV) were detected by an enzyme immunoassay using infected cell cultures as antigen in the sera of 33 patients from both genera and 6-65 years old. MAYV genome was also detected by RT-PCR in the blood of 1/33 of these patients. The patients presented mainly with headache, arthralgia, myalgia, ocular pain, and rash. These cases of Mayaro fever are likely to represent the tip of an iceberg, and probably a much greater number of cases occurred in Manaus in the study period.

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.

The SARS-CoV-2 lineage B.1.1.28 has been evolving in Brazil since February 2020 giving origin to multiple local clades including the new Variant of Concern (VOC) designated P.1 or 501Y.V3. The recent emergence of sub-lineages with convergent mutations in the spike (S) protein raises concern about the potential impact on viral infectivity and immune escape. We describe here the first three confirmed SARS-CoV-2 reinfections cases with the new VOC P.1 in residents of the Amazonas state, Brazil. Three female patients, 29, 40, and 50-year-old, were RT-PCR confirmed for SARS-CoV-2 on two occasions, with at least 92 days apart. Next-generation sequencing and phylogenetic analysis were conducted to precisely access the SARS-CoV-2 lineages of each infection event. SARS-CoV-2 genomic analysis confirmed three cases of reinfections caused by the VOC P.1 in patients that were primo-infected by distinct viral lineages 3–9 months earlier. Case 1 (29-year-old) was positive on March 24, 2020 (lineage B.1.195) and then on December 30, 2020 (lineage P.1); case 2 (50-year-old) was positive on October 19, 2020 (lineage B.1.1.33) and on January 19, 2021 (lineage P.1); case 3 (40-year-old) was positive on April 22, 2020 (lineage B.1.195) and on January 29, 2021 (lineage P.1). The three patients displayed low mean Ct values (< 22) at nasopharyngeal samples and reported less severe illness during reinfection. The present study provides the first evidence of the new VOC P.1 causing multiple reinfections during the second epidemic peak in the Amazonas state. Our findings suggest that reinfected individuals may have been infectious. Although immune responses induced by natural infections do not necessarily prevent subsequent infections by the VOC P.1, they may still protect from severe disease.