Genomic epidemiology of the early stages of the SARS-CoV-2 outbreak in Russia

Abstract

The ongoing pandemic of SARS-CoV-2 presents novel challenges and opportunities for the use of phylogenetics to understand and control its spread. Here, we analyze the emergence of SARS-CoV-2 in Russia in March and April 2020. Combining phylogeographic analysis with travel history data, we estimate that the sampled viral diversity has originated from at least 67 closely timed introductions into Russia, mostly in late February to early March. All but one of these introductions were not from China, suggesting that border closure with China has helped delay establishment of SARS-CoV-2 in Russia. These introductions resulted in at least 9 distinct Russian lineages corresponding to domestic transmission. A notable transmission cluster corresponded to a nosocomial outbreak at the Vreden hospital in Saint Petersburg; phylodynamic analysis of this cluster reveals multiple (2-3) introductions each giving rise to a large number of cases, with a high initial effective reproduction number of 3.0 [1.9, 4.3].

Fig. 1. Early epidemiology of SARS-CoV-2 in the Russian Federation.

a The number of confirmed cases (a, red) and number of sequenced complete genomes (a, gray circles) per region of the Russian Federation (including the Republic of Crimea) as of May 26. Circle sizes are proportional to the numbers of obtained sequences, which are also shown next to the circles. For the purpose of this figure, Moscow was pooled with the surrounding Moscow Region, and Saint Petersburg was pooled with the surrounding Leningrad Region. b Identified Russian lineages and corresponding regions; circle size is proportional to the number of sequences belonging to the lineage at this region, and lineages spanning multiple regions are connected by lines. The initial map of Russian regions was downloaded from GADM.

Fig. 2. Phylogeny of SARS-CoV-2 in Russia.

Russian sequences are identified with dots and highlighted in gray. Russian transmission lineages are truncated to the founder node and highlighted with color (the color scheme is consistent between Figs. 1–2 and 4–6). Major SARS-CoV-2 lineages are labeled according to Nextstrain and PANGOLIN|GISAID nomenclature in red and blue, respectively. Non-Russian sequences and lineages carrying no Russian sequences are truncated, with numbers of such sequences shown in brackets. Sequences from the Vreden hospital and lineages carrying such sequences are marked with star, triangle and diamonds. Branch lengths represent the number of nucleotide substitutions. “hCoV-19/” prefixes are excluded from all sample names for clarity. For readability, the B.1.1 lineage is collapsed (dashed line) and shown separately in Fig. 3.

Fig. 3. Phylogeny of SARS-CoV-2 in Russia, lineage B.1.1.

Notation is the same as in Fig. 2. The inset summarizes the distribution of Russian singletons, stem clusters and transmission lineages across major SARS-CoV-2 clades.

Fig. 4. Terminology for phylogenetic groups of samples.

We categorized Russian samples into five categories: Russian transmission lineage-set of two or more sequences that form a Russian-only clade; Russian singleton-single Russian sequence that forms a clade of its own and is not a part of a Russian transmission lineage; Russian stem cluster-set of Russian sequences identical to each other and to some non-Russian sequences; Russian stem-derived transmission lineage-a Russian transmission lineage whose immediate ancestor is a Russian stem cluster; and Russian stem-derived singleton-Russian singleton whose immediate ancestor is a Russian stem cluster.

Fig. 5. Examples of Russian transmission lineages.

Only the phylogeny of the Russian transmission lineage is shown, together with its ancestral phylogenetic node. Russian sequences are marked with dots and highlighted in gray. All other sequences corresponding to an ancestral node (black vertical line) or descendant from it (black rectangle) are truncated, with the region/country and the earliest collection date shown. a Lineage 1, a lineage endemic to Saint Petersburg, includes an individual with a history of travel to Spain. b Lineage 4 includes individuals with travel history to two different countries, suggesting recurrent introduction. c The ancestral node of lineage 3 uniquely maps to Switzerland. d The ancestral node of lineage 9 uniquely maps to the USA, and this lineage spans two different regions of Russia. Flags represent individuals with a known history of travel to the corresponding country; the Russian flag shows a known lack of travel history. Diamonds represent samples associated with group 3 of the Vreden hospital outbreak. See Supplementary Fig. 1 for all nine transmission lineages.

Fig. 6. Examples of Russian singletons and stem clusters.

Notation is the same as in Fig. 5. a The singleton obtained from a patient with known travel history to France has French and Danish sequences at the ancestral node, with French sequences having an earlier collection date. b A sIngleton with a uniquely Saudi Arabian ancestral node. c A singleton with known absence of travel history. d A stem cluster with associated stem-derived singletons where multiple introductions were observed. See Supplementary Figs. 2–4 for all singletons and stem clusters.

Fig. 7. The timeline of SARS-CoV-2 introduction into Russia.

Depending on their phylogenetic position, Russian samples are classified as belonging to Russian transmission lineages, singletons or stem clusters (Fig. 4). Circles correspond to Russian samples colored by category. a Number of new registered COVID-19 cases per day in Russia between March 5 and April 30. b Correlation between sample collection date and patient age. The linear fit (r = 0.32; p = 3.9 × 10^-6) is shown (blue line), with the 95% confidence interval indicated as a shaded area. Spearman correlation coefficient is shown. c Estimated introduction dates for Russian transmission lineages, singletons and stem clusters. The circle size is proportional to the number of samples. Black lines correspond to the full date range. For each Russian transmission lineage, the indicated date corresponds to the collection date of the earliest sample. For stem-derived Russian transmission lineages (lineages 4, 6, 7, and 8), the earliest date of the corresponding stem cluster is also shown with a gray dot.

Fig. 8. Vreden hospital outbreak parameter estimates produced by birth-death skyline model in BEAST2.

Panels show posterior distributions of effective reproductive number R_e (upper panel) with the dashed vertical line corresponding to R_e = 1 and the date of the MRCA (lower panel) for analyses based on Vreden hospital samples from groups 1, 2, and 3 (left column), groups 1 and 2 (middle column) and group 1 (right column).

Fig. 9. Maximum clade credibility tree for the Vreden hospital outbreak.

Groups 1, 2, and 3 are marked by a star, a triangle and a diamond, respectively. Pink bars represent 95% credible intervals. The timeline of the outbreak is shown in gray, with the time interval from patient zero (March 27) till the introduction of quarantine (April 8) highlighted with a darker tone.