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However, understanding the relationship between host factors and viral replication deepens our understanding of viral fitness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In CoVPN 5001, we enrolled\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009953 adults diagnosed with acute SARS-CoV-2 from July 2020 to July 2022 across 51 sites. We confirmed SARS-CoV-2 infection by RT-PCR and identified the variant via viral genome sequencing. Using multivariable linear regression and median regression, we studied the association between host factors and either observed peak viral load (VL) or clinical viral shedding, respectively, accounting for viral variant effects in a demographically and clinically diverse longitudinal cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this observational study, we determine that while host factors, including age, BMI, sex, medical comorbidities, and HIV, have no significant associations with either observed peak VL or clinical viral shedding in the nasopharynx, viral variant is significantly associated with observed peak VL and clinical viral shedding. We show that neither observed peak VL nor shedding duration predict evolutionary success since the dominant variants in the SARS-CoV-2 pandemic did not all align with the variants with the highest peak and longest shedding duration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Altogether, our work shows that observed peak VL and shedding duration should be cautiously interpreted as predictors of viral fitness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s43856-026-01588-5","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T12:46:55Z","timestamp":1776430015000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Viral variant but not host factors associate with SARS-CoV-2 viral 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J.P. reports institutional research grant support from NIH, Janssen, Inc., Gilead Sciences, Inc., and ViiV Healthcare and personal fees for advisory boards from GSK\/ViiV, all outside the submitted work. C.Y. is employed by NIAID\/NIH, the funder and Sponsor of the study described in this manuscript, and served as one of the Medical Officers for the study. P.C. reports consulting fees received from ViiV Healthcare and Gilead, outside of the present study. L.S.C. reports consulting fees received from ViiV Healthcare outside of the present study. C.F.K. reports research grants to her institution from Moderna, Novavax, Humanigen, Gilead, and Viiv. N.R. reports institutional support from the NIH, Merck, Sanofi, Pfizer, Vaccine Company, Immorna, personal fees from Krog, Virology Education, Sanofi, and Moderna, and served on advisory boards for Moderna, Sanofi, Seqirus, Pfizer, EMMES, ICON, BARDA, CyanVac, and Micron Safety, all outside of the present study. All other authors have no conflicts of interest to report.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All collaborators of this study have fulfilled the criteria for authorship required by Nature Portfolio journals and have been included as authors. This work includes findings that are globally relevant, which have been determined in collaboration with local partners, many of whom are co-authors on the manuscript. We feel that it does not result in stigmatization, incrimination, discrimination, or personal risk to participants. As the work reflects the global COVID pandemic to date, local and regional research was integral to our study and we have included representative examples in the citations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Inclusion and Ethics"}}],"article-number":"346"}}