Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Cell. 2021 Jan 7;184(1):64-75.e11. doi: 10.1016/j.cell.2020.11.020. Epub 2020 Nov 19.

Abstract

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.

Keywords: COVID-19; SARS-CoV-2; epidemiology; evolution; founder effect; spike.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution*
  • Aspartic Acid / analysis
  • Aspartic Acid / genetics
  • COVID-19 / epidemiology
  • COVID-19 / transmission*
  • COVID-19 / virology*
  • Genome, Viral
  • Glycine / analysis
  • Glycine / genetics
  • Humans
  • Mutation
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / growth & development
  • SARS-CoV-2 / pathogenicity*
  • Spike Glycoprotein, Coronavirus / genetics*
  • United Kingdom / epidemiology
  • Virulence
  • Whole Genome Sequencing

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Aspartic Acid
  • Glycine