SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate

Int J Clin Pract. 2020 Aug;74(8):e13525. doi: 10.1111/ijcp.13525. Epub 2020 Jun 3.


Aim: The COVID-19 pandemic is caused by infection with the SARS-CoV-2 virus. The major mutation detected to date in the SARS-CoV-2 viral envelope spike protein, which is responsible for virus attachment to the host and is also the main target for host antibodies, is a mutation of an aspartate (D) at position 614 found frequently in Chinese strains to a glycine (G). We sought to infer health impact of this mutation.

Result: Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilise a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.

Conclusion: These results imply that G614 is a more pathogenic strain of SARS-CoV-2, which may influence vaccine design. The prevalence of this form of the virus should also be included in epidemiologic models predicting the COVID-19 health burden and fatality over time in specific regions. Physicians should be aware of this characteristic of the virus to anticipate the clinical course of infection.

MeSH terms

  • Aspartic Acid
  • Betacoronavirus / genetics*
  • Betacoronavirus / pathogenicity
  • Binding Sites
  • COVID-19
  • Coronavirus Infections / mortality*
  • Glycine
  • Humans
  • Mutation*
  • Pandemics
  • Pneumonia, Viral / mortality*
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / genetics*


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