Tracking down the origin and subsequent spread of SARS-CoV-2 lineage B.1.619

Abstract

Since late 2020, the emergence of variants of concern (VOCs) of SARS-CoV-2 has been of concern to public health, researchers and policymakers. Mutations in the SARS-CoV-2 genome-for which clear evidence is available indicating a significant impact on transmissibility, severity and/or immunity-illustrate the importance of genomic surveillance and monitoring the evolution and geographic spread of novel lineages. Lineage B.1.619 was first detected in Switzerland in January 2021, in international travellers returning from Cameroon. This lineage was subsequently also detected in Rwanda, Belgium, Cameroon, France, and many other countries and is characterised by spike protein amino acid mutations N440K and E484K in the receptor binding domain, which are associated with immune escape and higher infectiousness. In this study, we perform a phylogeographic analysis to track the geographic origin and subsequent dispersal of SARS-CoV-2 lineage B.1.619. We employ a recently developed travel history-aware phylogeographic model, enabling us to incorporate genomic sequences with associated travel information. We estimate that B.1.619 most likely originated in Cameroon, in November 2020. We estimate the influence of the number of air-traffic passengers on the dispersal of B.1.619 but find no significant effect, illustrative of the complex dispersal patterns of SARS-CoV-2 lineages. Finally, we examine the metadata associated with infected Belgian patients and report a wide range of symptoms and medical interventions.

Keywords: B.1.619; Bayesian inference; COVID-19; GLM; Markov chain Monte Carlo; SARS-CoV-2; air traffic; phylogenetics; phylogeography.

Figure 1

Known locations and travel history of B.1.619 cases. Collection dates of B.1.619 genomes are shown for each country (rows). Genomes from travellers are outlined with colour indicating travel of origin (e.g. dark red for Cameroon) and connected to a smaller dot indicating which country’s diversity is being sampled at travel destination. Bars at the top indicate the number of genomes of B.1.619 available for a given date across all countries. Of note, 46 B.1.619 genomes from Canada were not included due to imprecise collection dates. On January 20, 2021, a single B.1.619 case was found in Rwanda; the travel case on May 1, 2021, was entering Japan from South Korea.

Figure 2

Lineage-defining SNPs of lineage B.1.619. Only SNPs that differentiate B.1.619 (genomes within the dashed line box) from the reference and are shared by at least two B.1.619 genomes are shown in the condensed SNP alignment. Representative genomes from lineage B.1.620 are included for comparison. Sites identical to the reference (GenBank accession NC_045512) are shown in grey, changes from the reference are indicated and coloured by nucleotide (green for thymine, red for adenosine, blue for cytosine, yellow for guanine, dark grey for ambiguities, black for gaps). If a mutation results in an amino acid change, the column label indicates the gene, reference amino acid, amino acid site, and amino acid change in brackets. The phylogeny (branch lengths number of mutations) on the right shows the relationships between depicted genomes and was rooted on the reference sequence.

Figure 3

Maximum clade credibility trees of lineage B.1.619 coloured by reconstructed location using the latest available data as of June 2021. (A) Global phylogeny of SARS-CoV-2 genomes with branches coloured by inferred continent from a Bayesian phylogeographic analysis that makes use of individual travel histories. An asterisk indicates the root for the B.1.619 clade. Lineage B.1.619 is outlined and a horizontal bar shows the posterior probability of its common ancestor existing in a given continent. Africa is reconstructed as the most likely location (posterior probability 0.995) where B.1.619 originated. (B) Phylogeny of lineage B.1.619 with branches coloured by inferred country from a Bayesian phylogeographic analysis that makes use of travel histories. In this analysis Cameroon and Central African Republic (CAR) are reconstructed as the most likely locations (with posterior probabilities of 0.81 and 0.17, respectively) of the common ancestor of lineage B.1.619. Larger white dots at nodes indicate nodes with posterior probability of at least 95 per cent, while smaller grey circles indicate nodes with posterior probability of at least 50 per cent.

Figure 4

Markov jumps plot showing the number of B.1.619 transition events between countries. Countries of origin are shown in the columns, destination countries are shown in the rows. We see most jumps from both Cameroon and Belgium into Germany and France. Cameroon also seeds infections in other countries such as the USA, Switzerland, Rwanda and Belgium (among others).

Figure 5

Identified predictors for the spread of B.1.619 We see that the only variable with a significant negative effect on the spread of B.1.619 is ‘distance’. This means we estimate a reduced probability of seeing a transition event between country pairs with a larger distance between them. We see no effect at all for the number of flights between country pairs.

Figure 6

Spatially-explicit phylogeographic reconstruction of the dispersal history of the B.1.619 lineage in Belgium. Nodes are coloured from blue (the time of the most recent common ancestor, tMRCA) to red (most recent sampling time). The dispersal of B.1.619 within Belgium was characterized by both.

Figure 7

Patient data concerning symptoms, vaccination status and health outcomes. We show the symptoms reported for each Belgian patient infected with B.1.619, coloured according to the number of symptoms (of each patient; each row represents one patient). The three columns on the right show whether or not patients were hospitalised, and if they received oxygen therapy or spend time in the intensive care unit (ICU). The stars indicate patients that were vaccinated, with the two red colored stars indicating cases of post-vaccination infection.

Figure 8

Within-Africa air passenger flux matrix and outward flux (from African countries) to the rest of the world. Columns of the matrix represent destination locations within Africa while the plot above the matrix indicates the continental breakdown of flights leaving that African country directly, e.g.. the vast majority of passengers flying from Morocco travel directly to Europe. Rows of the matrix represent origin locations within Africa. The plot to the right of the matrix indicates, for every row country, which continents it is likely to connect with secondarily, e.g. flights departing South Africa mostly land in countries that later send most of their passengers to African countries, while for Sudan it is Asia and for Libya it is Europe.