Could the D614G substitution in the SARS-CoV-2 spike (S) protein be associated with higher COVID-19 mortality?

Abstract

The increasing number of deaths due to the COVID-19 pandemic has raised serious global concerns. Increased testing capacity and ample intensive care availability could explain lower mortality in some countries compared to others. Nevertheless, it is also plausible that the SARS-CoV-2 mutations giving rise to different phylogenetic clades are responsible for the apparent death rate disparities around the world. Current research literature linking the genetic make-up of SARS-CoV-2 with fatalities is lacking. Here, we suggest that this disparity in fatality rates may be attributed to SARS-CoV-2 evolving mutations and urge the international community to begin addressing the phylogenetic clade classification of SARS-CoV-2 in relation to clinical outcomes.

Keywords: COVID-19; Coronavirus; D614G; S-Protein; SARS-CoV-2.

Figure 1

(A) Unrooted phylogenetic tree with clear distinction of the 614G and 614D clades at the S protein site (https://nextstrain.org/ncov; last accessed May 2, 2020). (B) Bar plot showing the total number of deaths per million populaces (https://www.worldometers.info/coronavirus/; last accessed May 2, 2020). The map inside the box plot presents the distribution of S-614G and the wild-type S-614D in European populations (https://nextstrain.org/ncov; last accessed May 2, 2020) labeled in the y-axis of the bar plot.

Figure 2

The mutation observed at the S protein of the SARS-COV-2, D614G in white color, may create conformational changes mimicking the open status and facilitate the cleavage domain’s exposure to proteases FURIN or TMPRSS2 and could be sufficient to speed up the cleavage.