Morning SARS-CoV-2 Testing Yields Better Detection of Infection Due to Higher Viral Loads in Saliva and Nasal Swabs upon Waking
Abstract
Optimizing specimen collection methods to achieve the most reliable SARS-CoV-2 detection for a given diagnostic sensitivity would improve testing and minimize COVID-19 outbreaks. From September 2020 to April 2021, we performed a household-transmission study in which participants self-collected specimens every morning and evening throughout acute SARS-CoV-2 infection. Seventy mildly symptomatic participants collected saliva, and of those, 29 also collected nasal swab specimens. Viral load was quantified in 1,194 saliva and 661 nasal swab specimens using a high-analytical-sensitivity reverse transcription-quantitative PCR (RT-qPCR) assay. Viral loads in both saliva and nasal swab specimens were significantly higher in morning-collected specimens than in evening-collected specimens after symptom onset. This aspect of the biology of SARS-CoV-2 infection has implications for diagnostic testing. We infer that morning collection would have resulted in significantly improved detection and that this advantage would be most pronounced for tests with low to moderate analytical sensitivity. Collecting specimens for COVID-19 testing in the morning offers a simple and low-cost improvement to clinical diagnostic sensitivity of low- to moderate-analytical-sensitivity tests. Importance: Our findings suggest that collecting saliva and nasal swab specimens in the morning immediately after waking yields higher SARS-CoV-2 viral loads than collection later in the day. The higher viral loads from morning specimen collection are predicted to significantly improve detection of SARS-CoV-2 in symptomatic individuals, particularly when using moderate- to low-analytical-sensitivity COVID-19 diagnostic tests, such as rapid antigen tests.
Additional Information
We sincerely thank the study participants for making this work possible. We thank Lauriane Quenee, Grace Fisher-Adams, Junie Hildebrandt, Megan Hyashi, 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. We thank Jessica Leong, Jessica Slagle, Mika Walton, Angel Navarro, Daniel Brenner, Ojas Pradhan, Si Hyung Jin, and Mary Arrastia for volunteering their time to help with this study. We thank Angie Cheng, Susan Magdaleno, Christian Kis, Monica Herrera, and Zaina Lemeir for technical discussions regarding saliva extraction and detection. We thank Jennifer Fulcher, Debika Bhattacharya, and Matthew Bidwell Goetz for their ideas on potential study populations and early study design. We thank Omai Garner and David Beenhouwer for providing materials for initial nasal swab validation. We thank Martin Hill, Alma Sanchez, Scott Kim, Debbie Noble, Nina Paddock, Whitney Harrison, Emily Holman, Isaac Turner, Vivek Desai, Luke Wade, Tom Mayell, Stu Miller, Jennifer Howes, and Nari Shin for their support with recruitment. We thank Allison Rhines, Karen Heichman, and Dan Wattendorf for valuable discussions and guidance. We thank David Prober for discussions of circadian rhythms and feedback on the manuscript. Finally, we thank all the case investigators and contact tracers at the Pasadena Public Health Department, the City of Long Beach Department of Health & Human Services, and Caltech Student Wellness Services for their efforts in study recruitment and their work in the pandemic response. R.F.I. is a cofounder, consultant, and a director and has stock ownership of Talis Biomedical Corp. This study is based on research funded in part by the Bill & Melinda Gates Foundation (INV-023124). The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. This work was also funded by the Ronald and Maxine Linde Center for New Initiatives at the California Institute of Technology and the Jacobs Institute for Molecular Engineering for Medicine at the California Institute of Technology. A.V.W. is supported by a UCLA DGSOM Geffen Fellowship, and M.M.C. is supported by a Caltech Graduate Student Fellowship.Files
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Additional details
- PMCID
- PMC9769854
- Eprint ID
- 117825
- Resolver ID
- CaltechAUTHORS:20221110-430693700.10
- DOI
- 10.1128/spectrum.03873-22
- INV-023124
- Bill and Melinda Gates Foundation
- Ronald and Maxine Linde Center for New Initiatives
- Jacobs Institute for Molecular Engineering for Medicine
- UCLA
- Caltech
- Created
-
2022-11-23Created from EPrint's datestamp field
- Updated
-
2023-01-30Created from EPrint's last_modified field
- Caltech groups
- COVID-19, Jacobs Institute for Molecular Engineering for Medicine, Division of Biology and Biological Engineering