Genomic epidemiology of SARS-CoV-2 in Russia reveals recurring cross-border transmission throughout 2020.

In 2020, SARS-CoV-2 has spread rapidly across the globe, with most nations failing to prevent or substantially delay its introduction. While many countries have imposed some limitations on trans-border passenger traffic, the effect of these measures on the global spread of COVID-19 strains remains unclear. Here, we report an analysis of 3206 whole-genome sequences of SARS-CoV-2 samples from 78 regions of Russia covering the period before the spread of variants of concern (between March and November 2020). We describe recurring imports of multiple COVID-19 strains into Russia throughout this period, giving rise to 457 uniquely Russian transmission lineages, as well as repeated cross-border transmissions of local circulating variants out of Russia. While the phylogenetically inferred rate of cross-border transmissions was somewhat reduced during the period of the most stringent border closure, it still remained high, with multiple inferred imports that each led to detectable spread within the country. These results indicate that partial border closure has had little effect on trans-border transmission of variants, which helps explain the rapid global spread of newly arising SARS-CoV-2 variants throughout the pandemic.

SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19.

Evolution of SARS-CoV-2 in immunocompromised hosts may result in novel variants with changed properties. While escape from humoral immunity certainly contributes to intra-host evolution, escape from cellular immunity is poorly understood. Here, we report a case of long-term COVID-19 in an immunocompromised patient with non-Hodgkin's lymphoma who received treatment with rituximab and lacked neutralizing antibodies. Over the 318 days of the disease, the SARS-CoV-2 genome gained a total of 40 changes, 34 of which were present by the end of the study period. Among the acquired mutations, 12 reduced or prevented the binding of known immunogenic SARS-CoV-2 HLA class I antigens. By experimentally assessing the effect of a subset of the escape mutations, we show that they resulted in a loss of as much as ~1% of effector CD8 T cell response. Our results indicate that CD8 T cell escape represents a major underappreciated contributor to SARS-CoV-2 evolution in humans.

Spread of endemic SARS-CoV-2 lineages in Russia before April 2021.

In 2021, the COVID-19 pandemic was characterized by global spread of several lineages with evidence for increased transmissibility. Throughout the pandemic, Russia has remained among the countries with the highest number of confirmed COVID-19 cases, making it a potential hotspot for emergence of novel variants. Here, we show that among the globally significant variants of concern that have spread globally by late 2020, alpha (B.1.1.7), beta (B.1.351) or gamma (P.1), none have been sampled in Russia before the end of 2020. Instead, between summer 2020 and spring 2021, the epidemic in Russia has been characterized by the spread of two lineages that were rare in most other countries: B.1.1.317 and a sublineage of B.1.1 including B.1.1.397 (hereafter, B.1.1.397+). Their frequency has increased concordantly in different parts of Russia. On top of these lineages, in late December 2020, alpha (B.1.1.7) emerged in Russia, reaching a frequency of 17.4% (95% C.I.: 12.0%-24.4%) in March 2021. Additionally, we identify three novel distinct lineages, AT.1, B.1.1.524 and B.1.1.525, that have started to spread, together reaching the frequency of 11.8% (95% C.I.: 7.5%-18.1%) in March 2021. These lineages carry combinations of several notable mutations, including the S:E484K mutation of concern, deletions at a recurrent deletion region of the spike glycoprotein (S:Δ140-142, S:Δ144 or S:Δ136-144), and nsp6:Δ106-108 (also known as ORF1a:Δ3675-3677). Community-based PCR testing indicates that these variants have continued to spread in April 2021, with the frequency of B.1.1.7 reaching 21.7% (95% C.I.: 12.3%-35.6%), and the joint frequency of B.1.1.524 and B.1.1.525, 15.2% (95% C.I.: 7.6%-28.2%). Although these variants have been displaced by the onset of delta variant in May-June 2021, lineages B.1.1.317, B.1.1.397+, AT.1, B.1.1.524 and B.1.1.525 and the combinations of mutations comprising them that are found in other lineages merit monitoring.

The rise and spread of the SARS-CoV-2 AY.122 lineage in Russia.

Delta has outcompeted most preexisting variants of SARS-CoV-2, becoming the globally predominant lineage by mid-2021. Its subsequent evolution has led to the emergence of multiple sublineages, most of which are well-mixed between countries. By contrast, here we show that nearly the entire Delta epidemic in Russia has probably descended from a single import event, or from multiple closely timed imports from a single poorly sampled geographic location. Indeed, over 90 per cent of Delta samples in Russia are characterized by the nsp2:K81N + ORF7a:P45L pair of mutations which is rare outside Russia, putting them in the AY.122 sublineage. The AY.122 lineage was frequent in Russia among Delta samples from the start, and has not increased in frequency in other countries where it has been observed, suggesting that its high prevalence in Russia has probably resulted from a random founder effect rather than a transmission advantage. The apartness of the genetic composition of the Delta epidemic in Russia makes Russia somewhat unusual, although not exceptional, among other countries.