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Published March 2023 | Published + Supplemental Material
Journal Article Open

Extreme differences in SARS-CoV-2 viral loads among respiratory specimen types during presumed pre-infectious and infectious periods


SARS-CoV-2 viral-load measurements from a single-specimen type are used to establish diagnostic strategies, interpret clinical-trial results for vaccines and therapeutics, model viral transmission, and understand virus–host interactions. However, measurements from a single-specimen type are implicitly assumed to be representative of other specimen types. We quantified viral-load timecourses from individuals who began daily self-sampling of saliva, anterior-nares (nasal), and oropharyngeal (throat) swabs before or at the incidence of infection with the Omicron variant. Viral loads in different specimen types from the same person at the same timepoint exhibited extreme differences, up to 109 copies/mL. These differences were not due to variation in sample self-collection, which was consistent. For most individuals, longitudinal viral-load timecourses in different specimen types did not correlate. Throat-swab and saliva viral loads began to rise as many as 7 days earlier than nasal-swab viral loads in most individuals, leading to very low clinical sensitivity of nasal swabs during the first days of infection. Individuals frequently exhibited presumably infectious viral loads in one specimen type while viral loads were low or undetectable in other specimen types. Therefore, defining an individual as infectious based on assessment of a single-specimen type underestimates the infectious period, and overestimates the ability of that specimen type to detect infectious individuals. For diagnostic COVID-19 testing, these three single-specimen types have low clinical sensitivity, whereas a combined throat–nasal swab, and assays with high analytical sensitivity, was inferred to have significantly better clinical sensitivity to detect presumed pre-infectious and infectious individuals.

Additional Information

© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. The authors thank the study participants for making this work possible. The authors thank Lauriane Quenee, Grace Fisher-Adams, Junie Hildebrandt, Megan Hayashi, RuthAnne Bevier, Chantal D'Apuzzo, Ralph Adolphs, Victor Rivera, Steve Chapman, Gary Waters, Leonard Edwards, Gaylene Ursua, Cynthia Ramos, and Shannon Yamashita for their assistance and advice on study implementation and/or administration. They thank Jessica Leong, Ojas Pradhan, Si Hyung Jin, Emily Savela, Bridget Yang, Ekta Patel, Hsiuchen Chen, Paresh Samantaray, Zeynep Turan, Cindy Kim, Trinity Lee, Vanessa Mechan, Katherine Stiefel, Rosie Zedan, Rahulijeet Chadha, Minkyo Lee, and Jenny Ji for volunteering their time to help with this study. The authors thank Prabhu Gounder, Tony Chang, Jennifer Howes, and Nari Shin for their support with recruitment. Finally, the authors thank all the case investigators and contact tracers at the Pasadena Public Health Department and Caltech Student Wellness Services for their efforts in study recruitment and their work in the pandemic response. This manuscript was posted on the preprint server medRxiv at https://www.medrxiv.org/content/10.1101/2022.07.13.22277113v2. This work was funded in part by a grant from the Ronald and Maxine Linde Center for New Initiatives at the California Institute of Technology (to RFI), a grant from the Jacobs Institute for Molecular Engineering for Medicine at the California Institute of Technology (to RFI), and a DGSOM Geffen Fellowship at the University of California, Los Angeles (to AVW). Author contributions. Detailed author contributions are in the Supplement. Conceptualization: A.V.W., N.S., M.F., Y-Y.G., R.F.I.; methodology: A.V.W., R.A., N.S.; investigation: A.V.W., R.A., N.S., S.C., H.D., M.K.K., J.R.B.R., T.Y., A.E.R., A.M.C., Y.C.C.; visualization: A.V.W., R.A., N.S.; funding acquisition: A.V.W., R.F.I.; project administration: N.S., R.F.I.; supervision: Y.C.C., R.F.I.; writing—original draft: A.V.W., R.A., N.S. writing—review and editing: A.V.W., R.A., N.S., A.E.R., A.M.C., R.F.I. Data availability. The data underlying the results presented in the study can be accessed at CaltechDATA: https://data.caltech.edu/records/20223. A.V.W., R.A., and N.S. authors contributed equally to this report. Order of co-first authorship was determined by extent of contributions; see detailed Author Contributions statement in the supplement. Competing interest: R.F.I. is a co-founder, consultant, and director for and has stock ownership in Talis Biomedical Corporation. All other authors report no potential conflicts.

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Supplemental Material - pgad033_supplementary_data.zip


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Additional details

August 20, 2023
September 11, 2023