Study population and setting
This study described the emergence and spread of the SARS-CoV-2 501Y.V2 variant during the second wave of the South African epidemic. Daily COVID-19 case rates were obtained from publicly available databases maintained by the National Department of Health and the National Institute for Communicable Diseases. Phylogenetic analysis included SARS-CoV-2 genomic sequences (n=2,759) randomly sampled across South Africa between March and December 2020, and a global background sequence data set (n=2,753). 501Y.V2 variant sequences (n=341) collected between October and December 2020 were used to establish a mutation profile for the variant and to create a structural model of the variant spike protein.
Summary of Main Findings
The second wave of the South African COVID-19 epidemic started in October 2020, beginning with a resurgence of cases in the Nelson Mandela Bay region of the Eastern Cape (EC) and rapidly expanding to include both the Western Cape (WC) and KwaZulu-Natal (KZN). In response, genomic surveillance efforts were intensified in these provinces, leading to the identification of a new variant of concern (501Y.V2). By mid-November, 501Y.V2 became the predominant lineage in EC, WC, and KZN, and preliminary models indicate that its rate of transmission may be increased by as much as 50%. The 501Y.V2 variant contains eight lineage-defining non-synonymous mutations in the spike protein, three of which (K417N, E484K, and N501Y) correspond to the receptor binding domain and have previously been associated with either increased transmissibility or immune escape. Structural modeling demonstrated that two of these mutations (K417N, E484K) are found in key locations targeted by host neutralizing antibodies.
This study included a large dataset of randomly sampled SARS-CoV-2 whole genome sequences from South Africa, including 341 501Y.V2 sequences. Mutations specific to the 501Y.V2 variant were assessed using structural modeling, estimates of selection pressure, and prior studies.
Sequence metadata did not include location information, so health facility location was used to approximate the geographic origin for each sample. Additionally, functional relevance of lineage-defining mutations was assumed based on prior work describing the impact of individual mutations on variants from other areas. Although authors indicate that they have preliminary data supporting the 501Y.V2 variant’s ability to escape neutralization, these data were not presented here.
This work describes how high levels of SARS-CoV-2 transmission in South Africa led to the emergence and spread of a new variant of concern (501Y.52). This study also describes variant-defining mutations and explores their potential functional relevance in terms of both transmissibility and the ability of 501Y.V2 to evade host immune responses.