Patient-Derived Mutations Impact Pathogenicity of SARS-CoV-2

Abstract

The sudden outbreak of the severe acute respiratory syndrome–coronavirus (SARS-CoV-2) has spread globally with more than 1,300,000 patients diagnosed and a death toll of 70,000. Current genomic survey data suggest that single nucleotide variants (SNVs) are abundant. However, no mutation has been directly linked with functional changes in viral pathogenicity. We report functional characterizations of 11 patient-derived viral isolates. We observed diverse mutations in these viral isolates, including 6 different mutations in the spike glycoprotein (S protein), and 2 of which are different SNVs that led to the same missense mutation. Importantly, these viral isolates show significant variation in cytopathic effects and viral load, up to 270-fold differences, when infecting Vero-E6 cells. Therefore, we provide direct evidence that the SARS-CoV-2 has acquired mutations capable of substantially changing its pathogenicity. Funding: This work was supported by funds from Major Project of Zhejiang Provincial Science and Technology Department #2020C03123, National Science and Technology Major Project for the Control and Prevention of Major Infectious Diseases in China (2018ZX10711001, 2018ZX10102001, 2018ZX10302206), and start-606 up funds from Life Sciences Institute at Zhejiang University. Conflict of Interest: None. Ethical Approval: The study was approved by the Clinical Research Ethics Committee of The First Affiliated Hospital, School of Medicine, Zhejiang University (Approval notice 2020-29) for emerging infectious diseases.