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Emergence of a SARS-CoV-2 variant of concern with mutations in spike glycoprotein

Our take —

This study used daily case rates and genomic sequences sampled throughout South Africa from May to December 2020 to describe how the SARS-CoV-2 501Y.V2 variant arose in South Africa during the second wave of the nation’s epidemic. The 501Y.V2 variant contains new mutations that appear to lead to increased transmissibility of the virus and may allow for immune escape, although recent data released by Johnson & Johnson indicate that their COVID-19 vaccine still provides protection against 501Y.V2. Continuing to track viral genetic changes will allow public health entities to effectively respond to variants that increase transmission or immune escape. This work clearly illustrates how variants can emerge in areas with ongoing community transmission, reinforcing the importance of public health measures aimed at minimizing the spread of SARS-CoV-2.

Study design

Other

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.

Study Strengths

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.

Limitations

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.

Value added

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.

This review was posted on: 19 March 2021