Emergence and spread of SARS-CoV-2 lineage B.1.620 with variant of concern-like mutations and deletions

Abstract

Distinct SARS-CoV-2 lineages, discovered through various genomic surveillance initiatives, have emerged during the pandemic following unprecedented reductions in worldwide human mobility. We here describe a SARS-CoV-2 lineage - designated B.1.620 - discovered in Lithuania and carrying many mutations and deletions in the spike protein shared with widespread variants of concern (VOCs), including E484K, S477N and deletions HV69Δ, Y144Δ, and LLA241/243Δ. As well as documenting the suite of mutations this lineage carries, we also describe its potential to be resistant to neutralising antibodies, accompanying travel histories for a subset of European cases, evidence of local B.1.620 transmission in Europe with a focus on Lithuania, and significance of its prevalence in Central Africa owing to recent genome sequencing efforts there. We make a case for its likely Central African origin using advanced phylogeographic inference methodologies incorporating recorded travel histories of infected travellers.

Fig. 1. Lineage-defining SNPs of lineage B.1.620.

Only SNPs that differentiate B.1.620 (genomes outlined with a dashed line) from the reference (GenBank accession NC_045512) and that are shared by at least two B.1.620 genomes are shown in the condensed SNP alignment. Sites identical to the reference are shown in grey, changes from the reference are indicated and coloured by nucleotide (green for thymidine, red for adenosine, blue for cytosine, yellow for guanine, dark grey for ambiguities, black for gaps). The first 100 and the last 50 nucleotides are not included in the figure but were used to infer the phylogeny. 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 in the number of mutations) on the right shows the relationships between depicted genomes and was rooted on the reference sequence with coloured circles at the tips indicating the country from which the genome came. Posterior probabilities of nodes leading up to lineage B.1.620 are shown near each node with the long branch leading to lineage B.1.620 labelled as ‘B.1.620’.

Fig. 2. Maximum-likelihood tree of lineage B.1.620 in Europe.

Relationships between B.1.620 genomes, coloured by country of origin (same as Fig. 1) with a thicker coloured outline indicating the country of origin for travel cases. At least ten genomes shown (samples collected in Belgium, Switzerland, France and Equatorial Guinea) are from individuals who returned from Cameroon, one is from a traveller returning from Mali and one Lithuanian case returned from France. Genomes from the Central African Republic (CAR) and Czechia (returning traveller from Mali) are descended from the original B.1.620 genotype, while the genome from Equatorial Guinea is already closely related to genomes found in Europe and happens to be a travel case from Cameroon. Each genome is connected to the available geographic location in Europe with the smallest circles indicating municipality-level precision, intermediate size corresponding to county-level information (centred on county capital) and largest circle sizes indicating country-level information (centred on country capital). Countries are assigned the same colours as in Figs. 1 and 3.

Fig. 3. Known locations and travel history of B.1.620 cases.

Collection dates of B.1.620 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 the travel destination. Bars at the top indicate the number of genomes of B.1.620 available for a given date across all countries. Countries are assigned the same colours as in Fig. 1.

Fig. 4. Maximum clade credibility trees of lineage B.1.620 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. Lineage B.1.620 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.1.620 originated. The 95% and 50% highest posterior density (HPD) intervals for the most recent common ancestor date of lineage B.1.620 are indicated with violin plots centred on the common ancestor. B Phylogeny of lineage B.1.620 with branches coloured by inferred country from a Bayesian phylogeographic analysis that makes use of travel histories. A vertical bar shows posterior probabilities of where the common ancestor of B.1.620 existed. In this analysis, Central African Republic (CAR) and Cameroon are reconstructed as the most likely locations (with posterior probabilities of 0.805 and 0.168, respectively) of the common ancestor of lineage B.1.620. Larger white dots at nodes indicate nodes with a posterior probability of at least 95%, while smaller grey circles indicate nodes with a posterior probability of at least 50%. The 95% and 50% highest posterior density (HPD) intervals for the most recent common ancestor date of lineage B.1.620 are indicated with violin plots centred on the common ancestor.

Fig. 5. Total air passenger flows out of Cameroon (top) and Central African Republic (bottom) between December 2020 and April 2021.

Destination countries are sorted by total passenger volume arriving from Cameroon and Central African Republic (CAR) combined, coloured by continent (Europe in light blue, North America in dark blue, Africa in green, and Asia in red) and limited to countries where at least 100 passengers have arrived from either Cameroon or CAR between December 2020 and April 2021. Note the nearly order of magnitude greater passenger flux out of Cameroon compared to the Central African Republic (CAR). Numbers above each country’s bar indicate the total number of genomes on GISAID from that country since January 1st 2021, according to GISAID’s 2021-07-02 metadata release. Bars outlined in black represent countries that have submitted at least one B.1.620 genome as of June 2021.