{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:55:29Z","timestamp":1788245729262,"version":"build-2803163510"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T00:00:00Z","timestamp":1617840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI005157-01"],"award-info":[{"award-number":["AI005157-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1FI2GM137804-01"],"award-info":[{"award-number":["1FI2GM137804-01"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    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\n                    <jats:italic>in vitro<\/jats:italic>\n                    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\n                    <jats:sub>2<\/jats:sub>\n                    -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\n                    <jats:italic>in vivo<\/jats:italic>\n                    with the onset of humoral immunity, with the potential to contribute to delayed virologic clearance in the acute setting.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009431","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T13:28:31Z","timestamp":1617888511000},"page":"e1009431","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":38,"title":["High-throughput, single-copy sequencing reveals SARS-CoV-2 spike variants coincident with mounting humoral immunity during acute COVID-19"],"prefix":"10.1371","volume":"17","author":[{"given":"Sung 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