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.

Fig. 1.. SARS-CoV-2 epidemiological, diagnostic, genomic and mobility data from Manaus.

(A) Dark solid line shows the 7-day rolling average of the COVID-19 confirmed and suspected daily time series of hospitalisations in Manaus. Admissions in Manaus are from Fundação de Vigilância em Saúde do Amazonas (75). Green dots represent daily severe acute respiratory mortality records from the SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe) database (71). SARI = severe acute respiratory infections. Excess burial records based on data from Manaus Mayor’s office are shown in red dots for comparison (see Materials and Methods). The arrow denotes 6 December 2020, the date of the first P.1 case identified in Manaus by our study. (B) Maximum likelihood tree (n=974) with B.1.1.28, P.1 and P.2 sequences, with collapsed views of P.1 and P.2 clusters and highlighting other sequences from Manaus, Brazil). Ancestral branches leading to P.1 and P.2 are shown as dashed lines. See fig. S3 for a more detail phylogeny. Scale bar is shown in units of nucleotide substitutions per site (s/s). (C) Number of air travel passengers from Manaus to all states in Brazil was obtained from National Civil Aviation Agency of Brazil (www.gov.br/anac). The ISO 3166–2:BR codes of the states with genomic reports of P.1 (GISAID (76), as of 24 Feb 2021), are shown in bold. An updated list of GISAID genomes and reports of P.1 worldwide is available at https://covlineages.org/global_report_P.1.html. (D) Number of genome sequences from Manaus belonging to lineages of interest (see Materials and Methods); spike mutations of interest are denoted.

Fig. 2.. Visualization of the time-calibrated maximum clade credibility tree reconstruction for B.1.1.28, P.1 and P.2 lineages (n=974) in Brazil.

Terminal branches and tips of Amazonas state are coloured in brown and those from other locations are coloured in green. Nodes with posterior probabilities of <0.5 have been collapsed into polytomies and their range of divergence dates are illustrated as shaded expanses.

Fig. 3.. Temporal variation in the proportion of sequenced genomes belonging to P.1, and trends in RT-qPCR Ct values for COVID-19 infections in Manaus.

(A) Logistic function fitting to the proportion of genomes in sequenced infections that have been classified as P.1 (black circles, size indicating number of infections sequenced), divided up into time-periods where the predicted proportion of infections that are due to P.1 is <1/3 (light brown), between 1/3 and 2/3 (green) and greater than 2/3 (grey). For the model fit, darker ribbon represents the 50% credible interval, and lighter ribbon represents the 95% credible interval. For the data points, grey thick line is the 50% exact Binomial confidence interval and the thinner line is the 95% exact Binomial confidence interval. (B) Ct values for genes E and N in a sample of symptomatic cases presenting for testing at a healthcare facility in Manaus, stratified according to the period defined in (A) in which the oropharyngeal and nasal swab collections occurred in. (C) Ct values for genes E and N in a subsample of 184 infections included in (B) that had their genomes sequenced (dataset A).

Fig. 4.. Estimates of P.1’s epidemiological characteristics inferred from a multicategory Bayesian transmission model fitted to data from Manaus, Brazil

(A) Joint posterior distribution of the cross-immunity and transmissibility increase inferred through fitting the model to mortality and genomic data. Grey contours refer to posterior density intervals ranging from the 95% and 50% isoclines. Marginal posterior distributions for each parameter shown along each axis. (B) As for (A) but showing the joint-posterior distribution of cross-immunity and the inferred relative risk of morality in the period following P.1’s emergence compared to the period prior. (C) Daily incidence of COVID-19 mortality. Points show severe acute respiratory mortality records from the SIVEP-Gripe database (71), brown and green ribbons show model fit for COVID-19 mortality incidence, disaggregated by mortality attributable to non-P.1 lineages (brown) and the P.1 lineage (green). (D) Estimate of the proportion of P.1 infections through time in Manaus. Black data points with error bars are the empirical proportion observed in genomically sequenced cases (see Fig. 3A) and green ribbons (dark = 50% BCI, light = 95% BCI) the model fit to the data. (E) Estimated cumulative infection incidence for the P.1 and non-P.1 categories. Black data points with error bars are reversion-corrected estimates of seroprevalence from blood donors in Manaus (2), coloured ribbons are the model predictions of cumulative infection incidence for non-P.1 lineages (brown) and P.1 lineages (green). These points are shown for reference only and were not used to fit the model. (F) Bayesian posterior estimates of trends in reproduction number R_t for the P.1 and non-P.1 categories.