COVID-19 in Amazonas, Brazil, was driven by the persistence of endemic lineages and P.1 emergence

Abstract

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:

COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies

“…They found that NAbTs were 5.8-fold reduced against B.1.617.2 relative to wild type on a similar order to the reduction observed against B.1.351 [224]. B.1.617 partially evaded neutralization by the antibodies induced through natural infection or immunization with the BNT162b2 and mRNA-1273 vaccine, while sera from individuals having received one dose of AstraZeneca/Oxford (ChAdOx1) vaccine barely inhibited B.1.617.2 [214][215][216]. Convalescent sera from infected patients and from recipients of BBV152 (Covaxin) were able to neutralize B.1.617 partially, but the effect was robust, as seen with mRNA vaccines [214].…”

“…The P.1 variant has accumulated 12 mutations in the spike protein, including the N501Y mutation, which is also present in B.1.1.7 and B.1.351, while L18F, K417T, E484K and D614G mutations are shared with the B.1.351 variant (Figure 2B). Overall, P.1 contains 12 spike mutations in addition to D614G, including K417T, E484K and N501Y in the RBD, L18F, T20N, P26S, D138Y and R190S in the NTD, and H655Y near the furin cleavage site [214][215][216].…”

Predominance of SARS-CoV-2 P.1 (Gamma) lineage inducing the recent wave in southern Brazil and the finding of an additional S: D614A mutation

“…It has already been described that Gamma lineage can escape of the neutralization antibodies acquired by infection or immunization with previously circulating viral variants (de Souza et al, 2021) . As well, it was suggested that the Gamma is more transmissible than previously circulating lineages (Naveca et al, 2021) . These facts, in addition to the lack an e cient social distancing and other prevention measures probably caused the high numbers observed in this big SARS-CoV-2 wave.…”

“…Shortly thereafter, it was suggested that the Gamma is more transmissible. This fact in addition to the lack of e cient social distancing and other prevention measures probably caused the high hospitalizations (Naveca et al, 2021) . Also, it was observed rapid dissemination to other Brazilian regions as in Southern of Brazil where the Gamma variant would have already been identi ed, on November 30 This same phenomenon, characterized by a rapid spread had already been observed prior to March 2020.…”

COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies

“…The P.1 variant has accumulated 12 mutations in the spike protein including the N501Y mutation, which is also present in B.1.1.7 and B.1.351, while L18F, K417T, E484K, and D614G mutations are shared with the B.1.351 variant (Figure 2B). Overall, P.1 contains 12 spike mutations in addition to D614G, including K417T, E484K, and N501Y in the RBD, L18F, T20N, P26S, D138Y and R190S in the NTD, and H655Y near the furin cleavage site [204][205][206].…”