Open AccessHigh-throughput, single-copy sequencing reveals SARS-CoV-2 spike variants coincident with mounting humoral immunity during acute COVID-19
Author(s) -
Sung Hee Ko,
Elham Bayat Mokhtari,
Prakriti Mudvari,
Sydney Stein,
Christopher D. Stringham,
Danielle A. Wagner,
Sabrina Ramelli,
Marcos J. Ramos-Benítez,
Jeffrey R Strich,
Richard T. Davey,
Tongqing Zhou,
John Misasi,
Peter D. Kwong,
Daniel S. Chertow,
Nancy J. Sullivan,
Eli Boritz
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009431
Subject(s) - furin , biology , virology , virus , haplotype , coronavirus , genome , epitope , immunity , genetics , gene , antibody , immune system , genotype , covid-19 , disease , medicine , infectious disease (medical specialty) , biochemistry , pathology , enzyme
Tracking evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within infected individuals will help elucidate coronavirus disease 2019 (COVID-19) pathogenesis and inform use of antiviral interventions. In this study, we developed an approach for sequencing the region encoding the SARS-CoV-2 virion surface proteins from large numbers of individual virus RNA genomes per sample. We applied this approach to the WA-1 reference clinical isolate of SARS-CoV-2 passaged in vitro and to upper respiratory samples from 7 study participants with COVID-19. SARS-CoV-2 genomes from cell culture were diverse, including 18 haplotypes with non-synonymous mutations clustered in the spike NH 2 -terminal domain (NTD) and furin cleavage site regions. By contrast, cross-sectional analysis of samples from participants with COVID-19 showed fewer virus variants, without structural clustering of mutations. However, longitudinal analysis in one individual revealed 4 virus haplotypes bearing 3 independent mutations in a spike NTD epitope targeted by autologous antibodies. These mutations arose coincident with a 6.2-fold rise in serum binding to spike and a transient increase in virus burden. We conclude that SARS-CoV-2 exhibits a capacity for rapid genetic adaptation that becomes detectable in vivo with the onset of humoral immunity, with the potential to contribute to delayed virologic clearance in the acute setting.