SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo

Abstract

The spike D614G substitution is prevalent in global SARS-CoV-2 strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. The variant exhibits more efficient infection, replication, and competitive fitness in primary human airway epithelial cells, but maintains similar morphology and in vitro neutralization properties, compared with the ancestral wild-type virus. Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease. However, the D614G variant transmits significantly faster and displayed increased competitive fitness than the wild-type virus in hamsters. These data show that the D614G substitution enhances SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells and animal models.

Epidemic trends of SARS-CoV-2 associated with immunity, race, and viral mutations

“…Clades G, GR, and GH share the Spike: D614G mutation, which increases viral infectivity. 6,7 Therefore, these results suggest that the N: RG203KR/ORF14: G50N mutation in Clade GR and the ORF3a: Q57H mutation in Clade GH reduced the virulence of the Spike: D614G variant.…”

“…5b), consistent with increased viral infectivity. 6,7 In the early epidemics in China, the S type was the main type in areas other than Wuhan. 17 Due to the large number of Chinese workers working in Africa, the virus may have been introduced early.…”

“…Subsequent papers have revealed that this mutation also increases infectivity of the virus. 6,7 However, while Fermi estimates are useful for predicting the future in situations where timely action is required, it is known that differences in assumptions and inference methods can cause considerable errors in conclusions. In this study, "genetic fingerprinting" 8 was adopted for the epidemiological analyses of the current state of the pandemic.…”

Epidemic trends of SARS-CoV-2 associated with immunity, race, and viral mutations

“…Clade GR had a weak positive correlation with mortality (Spearman correlation coefficient ρ = 0.29, P = 0.021) and no significant correlation was observed with Clade GH (ρ = 0.028, P = 0.83). Clades G, GR, and GH share the Spike: D614G mutation, which increases viral infectivity (Hou et al, 2020;Plante et al, 2020).…”

“…To our knowledge, it was the first paper focusing on Spike: D614G. Subsequent papers have revealed that this mutation also increases infectivity of the virus (Hou et al, 2020;Plante et al, 2020).…”