4.8 Article

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

Journal

CELL
Volume 184, Issue 1, Pages 64-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2020.11.020

Keywords

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Funding

  1. MRC Centre for Global Infectious Disease Analysis [MR/R015600/1]
  2. European Commission [101003653]
  3. Biotechnology and Biological Sciences Research Council (BBSRC) [BB/M010996/1]
  4. Wellcome Trust (ARTIC network) [206298/Z/17/Z]
  5. European Research Council [725422 -ReservoirDOCS]
  6. MRC [MC_UU_1201412, MR/L015080/1]
  7. BBSRC [BB/M009122/1]
  8. BBSRC Institute Strategic Programme Microbes in the Food Chain [BB/R012504/1, BBS/E/F/000PR10348, BBS/E/F/000PR10352]
  9. Supercomputing Wales - European Regional Development Fund (ERDF) via Welsh Government
  10. Welsh Government
  11. BBSRC [BBS/E/F/000PR10352, BBS/E/F/000PR10348] Funding Source: UKRI
  12. MRC [MC_PC_19026, MR/L015080/1, MR/M009157/1, MR/J014370/1, MR/M006212/1, MC_UU_12014/3, MR/R015600/1, MC_PC_19012, MC_PC_19027] Funding Source: UKRI
  13. Wellcome Trust [206298/Z/17/Z] Funding Source: Wellcome Trust

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The study suggests a positive selection for the SARS-CoV-2 spike protein variant D614G in the UK, but no evidence of differences in COVID-19 mortality or clinical severity in patients infected with this variant. 614G is associated with higher viral load and younger age of patients compared to 614D.
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.

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