SARS-CoV-2 Viral Load in Saliva Rises Gradually and to Moderate Levels in Some Humans
Abstract
Transmission of SARS-CoV-2 in community settings often occurs before symptom onset, therefore testing strategies that can reliably detect people in the early phase of infection are urgently needed. Early detection of SARS-CoV-2 infection is especially critical to protect vulnerable populations who require frequent interactions with caretakers. Rapid COVID-19 tests have been proposed as an attractive strategy for surveillance, however a limitation of most rapid tests is their low sensitivity. Low-sensitivity tests are comparable to high sensitivity tests in detecting early infections when two assumptions are met: (1) viral load rises quickly (within hours) after infection and (2) viral load reaches and sustains high levels (>10⁵ - 10⁶ RNA copies/mL). However, there are no human data testing these assumptions. In this study, we document a case of presymptomatic household transmission from a healthy college student to his brother and father. Participants prospectively provided twice-daily saliva samples. Samples were analyzed by RT-qPCR and RT-ddPCR and we measured the complete viral load profiles throughout the course of infection of the brother and father. This study provides evidence that in at least some human cases of SARS-CoV-2, viral load rises slowly (over days, not hours) and not to such high levels to be detectable reliably by any low-sensitivity test. Additional viral load profiles from different samples types across a broad demographic must be obtained to describe the early phase of infection and determine which testing strategies will be most effective for identifying SARS-CoV-2 infection before transmission can occur.
Additional Information
The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. This version posted December 11, 2020. We thank Lauriane Quenee, Junie Hildebrandt, Grace Fisher-Adams, RuthAnne Bevier, Chantal D'Apuzzo, Ralph Adolphs, Victor Rivera, Steve Chapman, Gary Waters, Leonard Edwards, and Shannon Yamashita for their assistance and advice on study implementation or administration. We thank Jessica Leong, Jessica Slagle, and Angel Navarro for volunteering their time to help with this study. We thank Kissler et al. for making their data publicly available to the community. We thank Maira Phelps, Lienna Chan, Lucy Li and Amy Kistler at the Chan Zuckerberg Biohub for performing SARS-CoV-2 sequencing. We thank Jennifer Fulcher, Debika Bhattacharya and Matthew Bidwell Goetz for their ideas on potential study populations and early study design. We thank Martin Hill, Alma Sanchez, Scott Kim, Debbie Noble, Nina Paddock, Whitney Harrison, and Stu Miller for their support with recruitment. We thank Allison Rhines, Karen Heichman, and Dan Wattendorf for valuable discussion and guidance. Finally, we thank all the Pasadena Public Health Department case investigators and contact tracers for their efforts in study recruitment and their work in the pandemic response. This study is based on research funded in part by the Bill & Melinda Gates Foundation. 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 Jacobs Institute for Molecular Engineering for Medicine. AW is supported by an NIH NIGMS Predoctoral Training Grant (GM008042); MMC is supported by a Caltech Graduate Student Fellowship; and MP and JTB are each partially supported by National Institutes of Health Biotechnology Leadership Pre-doctoral Training Program (BLP) fellowships from Caltech's Donna and Benjamin M. Rosen Bioengineering Center (T32GM112592). Data Availability: Raw Ct values and calculated viral loads are available at CaltechDATA, https://data.caltech.edu/records/1702. Competing Interests Statement: The authors report grants from the Bill & Melinda Gates Foundation (to RFI) and the Jacobs Institute for Molecular Engineering for Medicine (to RFI), as well as a Caltech graduate fellowship (to MMC), two National Institutes of Health Biotechnology Leadership Pre-doctoral Training Program (BLP) fellowships (to MKP and JTB) from Caltech's Donna and Benjamin M. Rosen Bioengineering Center (T32GM112592), and a National Institutes of Health NIGMS Predoctoral Training Grant (GM008042) (to AW) during the course of the study. Dr. Ismagilov is a co-founder, consultant, and a director and has stock ownership and received personal fees from Talis Biomedical Corp., outside the submitted work. In addition, Dr. Ismagilov is an inventor on a series of patents licensed to Bio-Rad Laboratories Inc. in the context of ddPCR, with royalties paid. Author Declarations: I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes. The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was reviewed and approved by the Institutional Review Board of the California Institute of Technology, protocol #20-1026. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes. I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes. I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes.Attached Files
Submitted - 2020.12.09.20239467v1.full.pdf
Supplemental Material - media-1.pdf
Supplemental Material - media-2.pdf
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Additional details
- PMCID
- PMC7743094
- Eprint ID
- 107036
- Resolver ID
- CaltechAUTHORS:20201211-113537700
- Bill and Melinda Gates Foundation
- Jacobs Institute for Molecular Engineering for Medicine
- GM008042
- NIH Predoctoral Fellowship
- Donna and Benjamin M. Rosen Bioengineering Center
- T32GM112592
- NIH Predoctoral Fellowship
- Created
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2020-12-11Created from EPrint's datestamp field
- Updated
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2023-10-23Created from EPrint's last_modified field
- Caltech groups
- Rosen Bioengineering Center, Jacobs Institute for Molecular Engineering for Medicine, COVID-19, Division of Biology and Biological Engineering