Inferring effects of mutations on SARS-CoV-2 transmission from genomic surveillance data

Brian Lee, Ahmed Abdul Quadeer, Muhammad Saqib Sohail, Elizabeth Finney, Syed Faraz Ahmed, Matthew R. McKay () and John P. Barton ()
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Brian Lee: University of California, Riverside
Ahmed Abdul Quadeer: Hong Kong University of Science and Technology
Muhammad Saqib Sohail: Hong Kong University of Science and Technology
Elizabeth Finney: University of California, Riverside
Syed Faraz Ahmed: Hong Kong University of Science and Technology
Matthew R. McKay: Hong Kong University of Science and Technology
John P. Barton: University of California, Riverside

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract New and more transmissible variants of SARS-CoV-2 have arisen multiple times over the course of the pandemic. Rapidly identifying mutations that affect transmission could improve our understanding of viral biology and highlight new variants that warrant further study. Here we develop a generic, analytical epidemiological model to infer the transmission effects of mutations from genomic surveillance data. Applying our model to SARS-CoV-2 data across many regions, we find multiple mutations that substantially affect the transmission rate, both within and outside the Spike protein. The mutations that we infer to have the largest effects on transmission are strongly supported by experimental evidence from prior studies. Importantly, our model detects lineages with increased transmission even at low frequencies. As an example, we infer significant transmission advantages for the Alpha, Delta, and Omicron variants shortly after their appearances in regional data, when they comprised only around 1-2% of sample sequences. Our model thus facilitates the rapid identification of variants and mutations that affect transmission from genomic surveillance data.

Date: 2025
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DOI: 10.1038/s41467-024-55593-0

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