Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil

Abstract

Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite high levels of previous infection there. Through genome sequencing of viruses sampled in Manaus between November 2020 and January 2021, we identified the emergence and circulation of a novel SARS-CoV-2 variant of concern, lineage P.1, that acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around early November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.4–2.2 times more transmissible and 25-61% more likely to evade protective immunity elicited by previous infection with non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.One-Sentence SummaryWe report the evolution and emergence of a SARS-CoV-2 lineage of concern associated with rapid transmission in Manaus.

Detection of SARS-CoV-2 lineage P.1 in patients from a region with exponentially increasing hospitalisation rate, February 2021, Rio Grande do Sul, Southern Brazil

“…Until January 2021, the distribution of SARS-CoV-2 lineages observed in cases treated at our COVID-19 referral centre was similar to that observed in regional reports, which tended to follow the distribution of most Brazilian regions, except for the North, where lineage P.1 had been predominant since December 2020 [6,7]. In February 2021, however, an overwhelming increase in hospitalisations was observed from epidemiological week 6, temporally coinciding with the finding that lineage P.1 became predominant, accounting for the vast majority of specimens selected for genotyping in this period, albeit the number of specimens taken was small.…”

“…Since the hospitalisation dynamics observed in RS state resemble those noted in December in the northern states of Brazil, where P.1 vastly predominated among tested specimens, we hypothesise that P.1 might be at least partially associated with the striking 3.8-times rise in hospitalisations in RS. Previous findings suggesting that P.1 may be more transmissible than other lineages corroborate our hypothesis [7,9,11]. Regarding measures to control SARS-CoV-2 spread, in May 2020, the RS government implemented a system that divided the state into healthcare regions and, on a weekly basis, provided one of four possible classifications for each of such regions, thereby symbolising the risk of transmission.…”

Mutation hotspots, geographical and temporal distribution of SARS-CoV-2 lineages in Brazil, February 2020-2021: insights and limitations from uneven sequencing efforts

“…representing one of the most frequent lineages up to February 2021 (Faria et al 2021a;Naveca et al 2021) . Second, the fact that the set of mutations shared by P.1, B.1.1.7 and B.1.351 seem to have arisen independently, as we have previously demonstrated with emergence of E484K in others Brazilian lineages (P.2, B.1.1.28 and B.1.1.33), is suggestive of convergent molecular evolution (Ferrareze et al 2021;Faria et al 2021b) .…”

“…Additionally, virus exchanges between Amazonas and the urban metropolises in Southeast Brazil follow patterns in national air travel mobility, since states reporting P.1 until end-February 2021 received around 100,000 air passengers from Manaus in November. Of the 10 new amino acid mutations in the spike protein (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, H655Y, T1027I) compared to its immediate ancestor (B.1.1.28), molecular selection analyses found evidence that 9 of these 10 mutations are under diversifying positive selection (Faria et al 2021b) .…”

Pandemic moves and countermoves: vaccines and viral variants

“…Graver concerns about potential reductions in vaccine efficacy are presented by emerging variants other than B.1.1.7. 1 The Glu484Lys spike mutation, present in the P.1 and B.1.351 strains originating in Brazil and South Africa 10,11 and several other emerging strains, was not observed in the sequences analysed by Emary and colleagues because it was not circulating widely in the UK during the time of analysis. The Glu484Lys mutation is particularly important because it substantially reduces the neutralisation activity of monoclonal antibodies and serum samples from vaccinees or individuals infected with non-variant viruses.…”