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Morning SARS-CoV-2 Testing Yields Better Detection of Infection Due to Higher Viral Loads in Saliva and Nasal Swabs upon Waking

Winnett, Alexander Viloria and Porter, Michael K. and Romano, Anna E. and Savela, Emily S. and Akana, Reid and Shelby, Natasha and Reyes, Jessica A. and Schlenker, Noah W. and Cooper, Matthew M. and Carter, Alyssa M. and Ji, Jenny and Barlow, Jacob T. and Tognazzini, Colten and Feaster, Matthew and Goh, Ying-Ying and Ismagilov, Rustem F. (2022) Morning SARS-CoV-2 Testing Yields Better Detection of Infection Due to Higher Viral Loads in Saliva and Nasal Swabs upon Waking. Microbiology Spectrum, 10 (6). Art. No. e03873-22. ISSN 2165-0497. PMCID PMC9769854. doi:10.1128/spectrum.03873-22.

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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.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle ItemDiscussion Paper
Winnett, Alexander Viloria0000-0002-7338-5605
Porter, Michael K.0000-0002-0777-7563
Romano, Anna E.0000-0002-7148-0668
Savela, Emily S.0000-0001-9614-4276
Akana, Reid0000-0003-4422-587X
Shelby, Natasha0000-0001-9097-3663
Reyes, Jessica A.0000-0002-5507-7633
Schlenker, Noah W.0000-0002-8581-4403
Cooper, Matthew M.0000-0002-5868-5159
Carter, Alyssa M.0000-0002-2776-9421
Ji, Jenny0000-0002-7901-5605
Barlow, Jacob T.0000-0002-1842-4835
Tognazzini, Colten0000-0002-2754-3588
Feaster, Matthew0000-0001-9966-2845
Goh, Ying-Ying0000-0001-5136-7214
Ismagilov, Rustem F.0000-0002-3680-4399
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.
Group:COVID-19, Jacobs Institute for Molecular Engineering for Medicine
Funding AgencyGrant Number
Bill and Melinda Gates FoundationINV-023124
Ronald and Maxine Linde Center for New InitiativesUNSPECIFIED
Jacobs Institute for Molecular Engineering for MedicineUNSPECIFIED
Issue or Number:6
PubMed Central ID:PMC9769854
Record Number:CaltechAUTHORS:20221110-430693700.10
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:117825
Deposited By: Research Services Depository
Deposited On:23 Nov 2022 00:29
Last Modified:30 Jan 2023 21:25

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