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.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported. Methods We performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection. Findings For the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case-control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate. Interpretation Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented. Funding Fundação Oswaldo Cr...

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant P.1 emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread P.1 transmission has not been reported. Methods We performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where P.1 accounted for 75% of genotyped SARS-CoV-2 samples at the peak of its epidemic. Information from electronic surveillance databases was used to select cases of RT-PCR-confirmed SARS-CoV-2 infection and matched test-negative controls from 19 January, 2021 to 25 March, 2021. We used conditional logistic regression to estimate the effectiveness in reducing the odds of primary and secondary outcomes of, respectively, symptomatic and any SARS-CoV-2 infection. Findings Among 53,176 HCWs, 46,884 (88%) received at least one dose of CoronaVac and 2,656 (5%) underwent RT-PCR testing from 19 January, 2021 to 25 March, 2021. Of 2,797 RT-PCR tests, 776 (28%) were positive. 393 and 135 case-control pairs with and without, respectively, symptomatic illness were selected for the matched analyses. Vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, -6.6 - 60.5) in the same time period. Interpretation Administration of at least one dose of CoronaVac showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic P.1 transmission, underscoring the need to increase vaccination efforts in response to the spread of this variant in Brazil and globally. Funding Pan American Health Organization; Fundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus

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The continuous evolution of SARS-CoV-2 is an expected phenomenon that will continue to happen due to the high number of cases worldwide. The present study analyzed how a Variant of Concern (VOC) could still circulate in a population hardly affected by two COVID-19 waves and with vaccination in progress.

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Background In Brazil malaria is most frequent in the Amazon region, mainly in the Amazonas state, where it is found the most proportion of indigenous people of the whole country. It is remarkable publications about malaria in the Amazon, although information on malaria in indigenous populations is still poorly explored. Objective Identify factors associated with malaria in indigenous populations. Methods Cross-sectional study of positive cases of malaria in the state of Amazonas, Brazil, from 2007 to 2016. Secondary data were obtained from the Epidemiological Surveillance Information System for Malaria and from the Mortality Information System, both from Brazil. To tackle with race missing data, cases with no race fulfilled were classified according to the probable location where infection occurred. This way, was imputed indigenous race for those which the probable infection location was indigenous village (aldeia). Variables tested with race were: sex, age, schooling, microscope surveillance slide type, parasitic infection species, parasitemia level, and timeliness of treatment. Multivariate logistic regression was used. Results A total of 1,055,852 cases of malaria were notified in the state of Amazonas. Among the factors that associate malaria and indigenous peoples, the most significant were sex, children and high levels of parasitemia. The magnitude of Plasmodium vivax infection is higher than