{"doi":"10.1371/journal.ppat.1009431","title":"High-throughput, single-copy sequencing reveals SARS-CoV-2 spike variants coincident with mounting humoral immunity during acute COVID-19","abstract":"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 NH2-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.","journal":"PLoS Pathogens","year":2021,"id":157856,"datarank":0.5837730447165941,"base_score":3.8918202981106265,"endowment":3.8918202981106265,"self_citation_contribution":0.5837730447165941,"citation_network_contribution":0.0,"self_endowment_contribution":0.5837730447165941,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9163,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":267100,"name":"Elham Bayat Mokhtari","orcid":"0000-0002-6339-1673","position":1,"is_corresponding":false},{"id":618084,"name":"Prakriti Mudvari","orcid":"0000-0003-1888-402X","position":2,"is_corresponding":false},{"id":274360,"name":"Sydney Stein","orcid":"0000-0002-0259-4485","position":3,"is_corresponding":false},{"id":622893,"name":"Christopher D. Stringham","orcid":"0000-0003-0487-5157","position":4,"is_corresponding":false},{"id":622894,"name":"Danielle A. Wagner","orcid":"0000-0001-5819-1426","position":5,"is_corresponding":false},{"id":393088,"name":"Sabrina Ramelli","orcid":"0000-0001-5428-2814","position":6,"is_corresponding":false},{"id":274358,"name":"Marcos J. Ramos-Benítez","orcid":"0000-0001-9445-3294","position":7,"is_corresponding":false},{"id":237085,"name":"Jeffrey R. Strich","orcid":"0000-0002-5671-1130","position":8,"is_corresponding":false},{"id":104996,"name":"Richard T. Davey","orcid":"0000-0002-3992-5524","position":9,"is_corresponding":false},{"id":105631,"name":"Tongqing Zhou","orcid":"0000-0002-3935-4637","position":10,"is_corresponding":false},{"id":302423,"name":"John Misasi","orcid":"0000-0001-7169-2639","position":11,"is_corresponding":false},{"id":105633,"name":"Peter D. Kwong","orcid":"0000-0003-3560-232X","position":12,"is_corresponding":false},{"id":231243,"name":"Daniel S. Chertow","orcid":"0000-0002-1675-1728","position":13,"is_corresponding":false},{"id":266889,"name":"Nancy J. Sullivan","orcid":"0000-0002-2159-2039","position":14,"is_corresponding":false},{"id":291272,"name":"Eli Boritz","orcid":"0000-0003-4633-4594","position":15,"is_corresponding":false},{"id":291271,"name":"Sung Hee Ko","orcid":"0000-0002-4678-7449","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:44:21.786014Z","pmid":"33831133","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}