Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

TLDR

In Manaus, Brazil, SARS‑CoV‑2 cases resurged in late 2020 despite high prior infection, underscoring the need for enhanced global genomic surveillance of variants of concern to accelerate pandemic response. The study employed a two‑category dynamical model integrating genomic and mortality data. Genome sequencing revealed the P.1 lineage, carrying 17 mutations—including K417T, E484K, and N501Y in spike—emerged around mid‑November 2020, evolved rapidly, and appears 1.7‑ to 2.4‑fold more transmissible, while prior non‑P.1 infection confers 54‑79% protection against P.1.

Abstract

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-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 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against 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.