SARS-CoV-2 spike D614G variant exhibits highly efficient replication and transmission in hamsters

Mok, Bobo Wing-Yee; Cremin, Conor J.; Lau, Siu-Ying; Deng, Shaofeng; Chen, Pin; Zhang, Anna Jinxia; Lee, Andrew Chak-Yiu; Liu, Honglian; Liu, Siwen; Ng, Timothy Ting-Leung; Lao, Hiu-Yin; Lee, Eddie Lam-Kwong; Leung, Kenneth Siu-Sing; Wang, Pui; To, Kelvin Kai-Wang; Chan, Jasper Fuk-Woo; Chan, Kwok-Hung; Yuen, Kwok-Yung; Siu, Gilman Kit-Hang; Chen, Honglin

SARS-CoV-2 causes disease varying in severity from asymptomatic infections to severe respiratory distress and death in humans. The viral factors which determine transmissibility and pathogenicity are not yet clearly characterized. We used the hamster infection model to compare the replication ability and pathogenicity of five SARS-CoV-2 strains isolated from early cases originating in Wuhan, China, in February, and infected individuals returning from Europe and elsewhere in March 2020. The HK-13 and HK-95 isolates showed distinct pathogenicity in hamsters, with higher virus titers and more severe pathological changes in the lungs observed compared to other isolates. HK-95 contains a D614G substitution in the spike protein and demonstrated higher viral gene expression and transmission efficiency in hamsters. Intra-host diversity analysis revealed that further quasi species were generated during hamster infections, indicating that strain-specific adaptive mutants with advantages in replication and transmission will continue to arise and dominate subsequent waves of SARS-CoV-2 dissemination.