Viral variant but not host factors associate with SARS-CoV-2 viral kinetics
BACKGROUND: It is challenging to assess SARS-CoV-2 viral kinetics amidst viral variant evolution and changes in population-level immunity. However, understanding the relationship between host factors and viral replication deepens our understanding of viral fitness. METHODS: In CoVPN 5001, we enrolled N = 953 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. RESULTS: 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. CONCLUSIONS: Altogether, our work shows that observed peak VL and shedding duration should be cautiously interpreted as predictors of viral fitness.
Authors
- Shelly Ramirez
- Javier R. Lama (ORCID: https://orcid.org/0000-0002-4983-5725)
- Maphoshane Nchabeleng (ORCID: https://orcid.org/0000-0003-4385-8915)
- Hong‐Van Tieu (ORCID: https://orcid.org/0000-0002-7880-6448)
- Valeria D Cantos (ORCID: https://orcid.org/0000-0001-5447-3469)
- Leigh H. Fisher (ORCID: https://orcid.org/0000-0001-5228-1455)
- April K. Randhawa (ORCID: https://orcid.org/0000-0003-2652-3734)
- Wadzanai Samaneka (ORCID: https://orcid.org/0000-0003-0215-9309)
- Pavitra Roychoudhury (ORCID: https://orcid.org/0000-0002-4567-8232)
- Lameck Chinula (ORCID: https://orcid.org/0000-0003-3690-4207)
- Lynda Stranix‐Chibanda (ORCID: https://orcid.org/0000-0003-3566-1688)
- Nadine Rouphael (ORCID: https://orcid.org/0000-0002-2512-7919)
- Chishiba Kabengele (ORCID: https://orcid.org/0000-0003-0087-8596)
- Catherine Yen
- Nicole Espy (ORCID: https://orcid.org/0000-0002-4805-189X)
- Xiaohong Li (ORCID: https://orcid.org/0000-0003-4438-2664)
- Brenda Hoagland (ORCID: https://orcid.org/0000-0001-8210-3748)
- Lawrence Corey (ORCID: https://orcid.org/0000-0002-2179-2436)
- William Brumskine (ORCID: https://orcid.org/0000-0002-1092-9919)
- Muchaneta Bhondai‐Mhuri
- Khatija Ahmed (ORCID: https://orcid.org/0000-0003-0309-1641)
- Edgar García
- Marcelo Losso (ORCID: https://orcid.org/0000-0002-4273-4833)
- Mmatsie Manentsa
- Shannon Grant (ORCID: https://orcid.org/0000-0002-7297-8070)
- Colleen F. Kelley (ORCID: https://orcid.org/0000-0001-5611-0119)
- Ollivier Hyrien (ORCID: https://orcid.org/0000-0003-1909-2542)
- Amy Ward (ORCID: https://orcid.org/0000-0001-8430-0999)
- J Andrade Pinto
- John Hural
- Pedro E. Cahn
- William O. Hahn (ORCID: https://orcid.org/0000-0002-4613-0586)
- Joseph Makhema
- Jennifer Hanke
- Alexander L. Greninger
- Beatriz Grinsztejn
- Craig Innes
- Jorge A. Gallardo-Cartagena (ORCID: https://orcid.org/0000-0001-5142-1954)
- Carole L. Wallis
- Roma Chilengi
Institutions
- Universidade Federal de Minas Gerais (BR)
- University of North Carolina at Chapel Hill (US)
- Centre for Infectious Disease Research in Zambia (ZM)
- National Institutes of Health (US)
- Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA)
- Ministry of Health (ZM)
- NewYork–Presbyterian Hospital (US)
- New York Blood Center (US)
- Harvard University (US)
- Emory University (US)
- University of Zimbabwe (ZW)
- University of Cape Town (ZA)
- National University of San Marcos (PE)
- University of the Witwatersrand (ZA)
- Vanderbilt University (US)
- University of Washington (US)
- Asociación Civil Impacta Salud y Educación (PE)
- Columbia University Irving Medical Center (US)
- University of Washington Medical Center (US)
- Sefako Makgatho Health Sciences University (ZA)
- Universidad Nacional de la Amazonía Peruana (PE)
- Fred Hutch Cancer Center (US)
- Asociación para la Conservación de la Cuenca Amazónica (PE)
- Hospital Ramos Mejía (AR)
- Fundación Huésped (AR)
- Lancet Laboratories (ZA)
- HOPE Clinic (US)
- Aurum Institute (ZA)
- Zambia National Public Health Institute (ZM)
- National Institute of Allergy and Infectious Diseases (US)
- Botswana Harvard AIDS Institute Partnership (BW)
- Setshaba Research Centre (ZA)
- Fundação Oswaldo Cruz (BR)
- University of Pretoria (ZA)
Publication Details
- Journal
- Communications Medicine
- Published
- 2026-04-17
- DOI
- https://doi.org/10.1038/s43856-026-01588-5
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute of Allergy and Infectious Diseases