Ravi Gupta - March 17, 2021

Ravi Gupta, PhD, Professor of Clinical Microbiology, Cambridge Institute for Therapeutic Immunology and Infectious Diseases University of Cambridge, SARS-CoV-2 evolution during treatment of chronic infection and new variants

Focusing on the identification of SARS-CoV2’s Variants of Concern, Dr. Gupta’s team tracked the extent of viral mutations during 100 days of treating a patient with chronic infection of the virus or of new variants. Through whole genome sequencing, 23 respiratory samples were acquired over the entire treatment period, the proportion of reads with mutations over the duration was visualized to identify trends of various mutants, the infectivity of pseudoviruses containing the SARS-CoV2 Spike Protein and its mutations were tested, and the sensitivities of virus mutants to convalescent plasma (CP) and neutralizing antibodies were analyzed. Results showed that variants D796H and ΔH69/V70 were driven by the first and second treatment of CP, followed by loss and subsequent increase after the third treatment of CP; ΔH69/V70 arose in multiple lineages and usually proceeded RBD mutations. These results are the first real-time documentation of virus escape from antibody; they suggest that broad viral resistance to multiple sera may demonstrate a common pathway of antibody escape, and that chronic infection may be a likely source of new variants which can be used to foretell mutations.