Association of Trajectory of Viral RNA Load in SARS-CoV-2 G614 Infection With COVID-19 Symptoms | Infectious Diseases | JN Learning | AMA Ed Hub [Skip to Content]
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Infectious Diseases

Trajectory of Viral RNA Load Among Persons With Incident SARS-CoV-2 G614 Infection (Wuhan Strain) in Association With COVID-19 Symptom Onset and Severity

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
JAMA Network Open
January 10, 2022
Original Investigation
Helen C. Stankiewicz Karita, MD, MSc1;
Tracy Q. Dong, PhD2;
Christine Johnston, MD, MPH1,2,3;
Kathleen M. Neuzil, MD4;
Michael K. Paasche-Orlow, MD, MA, MPH5,6;
Patricia J. Kissinger, PhD, MPH7;
Anna Bershteyn, PhD8;
Lorna E. Thorpe, PhD8;
Meagan Deming, MD, PhD4;
Angelica Kottkamp, MD9;
Miriam Laufer, MD, MPH4,10;
Raphael J. Landovitz, MD, MSc11;
Alfred Luk, MD12;
Risa Hoffman, MD10;
Pavitra Roychoudhury, PhD2,3;
Craig A. Magaret, MS2,3;
Alexander L. Greninger, MD, PhD, MS, MPhil2,3;
Meei-Li Huang, PhD2;
Keith R. Jerome, MD, PhD2,3;
Mark Wener, MD3,13;
Connie Celum, MD, MPH1,14,15;
Helen Y. Chu, MD, MPH1,14,15;
Jared M. Baeten, MD, PhD1,14,15;
Anna Wald, MD, MPH1,2,3,15;
Ruanne V. Barnabas, MBChB, DPhil1,14,15;
Elizabeth R. Brown, ScD2,16,17
Author Affiliations
  • 1Division of Allergy and Infectious Diseases, University of Washington, Seattle
  • 2Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 3Department of Laboratory Medicine and Pathology, University of Washington, Seattle
  • 4Department of Medicine, University of Maryland School of Medicine, Baltimore
  • 5Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
  • 6Department of Medicine, Boston Medical Center, Boston, Massachusetts
  • 7Department of Epidemiology, Tulane University, New Orleans, Louisiana
  • 8Department of Population Health, New York University Grossman School of Medicine, New York
  • 9Department of Medicine, New York University Grossman School of Medicine, New York
  • 10Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore
  • 11Department of Medicine, University of California, Los Angeles, Los Angeles
  • 12Department of Medicine, Tulane University, New Orleans, Louisiana
  • 13Division of Rheumatology, University of Washington, Seattle
  • 14Department of Global Health, University of Washington, Seattle
  • 15Department of Epidemiology, University of Washington, Seattle
  • 16Department of Biostatistics, University of Washington, Seattle
  • 17Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
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Key Points

Question  What are the characteristics of SARS-CoV-2 G614 viral shedding in incident infections in association with COVID-19 symptom onset and severity?

Findings  In a cohort study of persons who tested positive for SARS-CoV-2 after recent exposure, viral RNA trajectory was characterized by a rapid peak followed by slower decay. Peak viral load correlated positively with symptom severity and generally occurred within 1 day of symptom onset if the patient was symptomatic.

Meaning  A detailed description of the SARS-CoV-2 G614 viral shedding trajectory serves as a baseline for comparison with new viral variants of concern and informs models to plan clinical trials to end the pandemic.

Abstract

Importance  The SARS-CoV-2 viral trajectory has not been well characterized in incident infections. These data are needed to inform natural history, prevention practices, and therapeutic development.

Objective  To characterize early SARS-CoV-2 viral RNA load (hereafter referred to as viral load) in individuals with incident infections in association with COVID-19 symptom onset and severity.

Design, Setting, and Participants  This prospective cohort study was a secondary data analysis of a remotely conducted study that enrolled 829 asymptomatic community-based participants recently exposed (<96 hours) to persons with SARS-CoV-2 from 41 US states from March 31 to August 21, 2020. Two cohorts were studied: (1) participants who were SARS-CoV-2 negative at baseline and tested positive during study follow-up, and (2) participants who had 2 or more positive swabs during follow-up, regardless of the initial (baseline) swab result. Participants collected daily midturbinate swab samples for SARS-CoV-2 RNA detection and maintained symptom diaries for 14 days.

Exposure  Laboratory-confirmed SARS-CoV-2 infection.

Main Outcomes and Measures  The observed SARS-CoV-2 viral load among incident infections was summarized, and piecewise linear mixed-effects models were used to estimate the characteristics of viral trajectories in association with COVID-19 symptom onset and severity.

Results  A total of 97 participants (55 women [57%]; median age, 37 years [IQR, 27-52 years]) developed incident infections during follow-up. Forty-two participants (43%) had viral shedding for 1 day (median peak viral load cycle threshold [Ct] value, 38.5 [95% CI, 38.3-39.0]), 18 (19%) for 2 to 6 days (median Ct value, 36.7 [95% CI, 30.2-38.1]), and 31 (32%) for 7 days or more (median Ct value, 18.3 [95% CI, 17.4-22.0]). The cycle threshold value has an inverse association with viral load. Six participants (6%) had 1 to 6 days of viral shedding with censored duration. The peak mean (SD) viral load was observed on day 3 of shedding (Ct value, 33.8 [95% CI, 31.9-35.6]). Based on the statistical models fitted to 129 participants (60 men [47%]; median age, 38 years [IQR, 25-54 years]) with 2 or more SARS-CoV-2–positive swab samples, persons reporting moderate or severe symptoms tended to have a higher peak mean viral load than those who were asymptomatic (Ct value, 23.3 [95% CI, 22.6-24.0] vs 30.7 [95% CI, 29.8-31.4]). Mild symptoms generally started within 1 day of peak viral load, and moderate or severe symptoms 2 days after peak viral load. All 535 sequenced samples detected the G614 variant (Wuhan strain).

Conclusions and Relevance  This cohort study suggests that having incident SARS-CoV-2 G614 infection was associated with a rapid viral load peak followed by slower decay. COVID-19 symptom onset generally coincided with peak viral load, which correlated positively with symptom severity. This longitudinal evaluation of the SARS-CoV-2 G614 with frequent molecular testing serves as a reference for comparing emergent viral lineages to inform clinical trial designs and public health strategies to contain the spread of the virus.

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Infectious Diseases Coronavirus (COVID-19)
Article Information

Accepted for Publication: November 14, 2021.

Published: January 10, 2022. doi:10.1001/jamanetworkopen.2021.42796

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Stankiewicz Karita HC et al. JAMA Network Open.

Corresponding Author: Helen C. Stankiewicz Karita, MD, Division of Allergy and Infectious Diseases, University of Washington, 325 Ninth Ave, Mailstop 359928, Seattle, WA 98104 (helensk@uw.edu).

Author Contributions: Drs Barnabas and Brown had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Stankiewicz Karita and Dong contributed equally to this work as co–first authors.

Concept and design: Stankiewicz Karita, Dong, Neuzil, Thorpe, Deming, Celum, Chu, Baeten, Wald, Brown.

Acquisition, analysis, or interpretation of data: Stankiewicz Karita, Dong, Johnston, Neuzil, Paasche-Orlow, Kissinger, Bershteyn, Thorpe, Kottkamp, Laufer, Landovitz, Luk, Hoffman, Roychoudhury, Magaret, Greninger, Huang, Jerome, Wener, Chu, Baeten, Wald, Barnabas, Brown.

Drafting of the manuscript: Stankiewicz Karita, Dong, Kissinger, Kottkamp, Wald, Brown.

Critical revision of the manuscript for important intellectual content: Stankiewicz Karita, Dong, Johnston, Neuzil, Paasche-Orlow, Kissinger, Bershteyn, Thorpe, Deming, Kottkamp, Laufer, Landovitz, Luk, Hoffman, Roychoudhury, Magaret, Greninger, Huang, Jerome, Wener, Celum, Chu, Baeten, Wald, Barnabas.

Statistical analysis: Dong, Magaret, Wald, Brown.

Obtained funding: Jerome, Celum, Baeten, Barnabas.

Administrative, technical, or material support: Stankiewicz Karita, Paasche-Orlow, Deming, Kottkamp, Laufer, Luk, Hoffman, Roychoudhury, Greninger, Huang, Jerome, Wener, Chu, Baeten, Wald.

Supervision: Johnston, Bershteyn, Thorpe, Kottkamp, Laufer, Roychoudhury, Greninger, Jerome, Chu, Baeten, Wald, Barnabas, Brown.

Conflict of Interest Disclosures: Dr Stankiewicz Karita reported receiving grants from the Bill & Melinda Gates Foundation and the National Cancer Institute at the National Institutes of Health (NIH) during the conduct of the study. Dr Dong reported receiving grants from the Bill & Melinda Gates Foundation during the conduct of the study. Dr Johnston reported receiving royalties from UpToDate; personal fees from AbbVie, Gilead, and MedPace; and grants from the Bill & Melinda Gates Foundation outside the submitted work. Dr Neuzil reported receiving grants from Pfizer grant to her institution for a COVID-19 vaccine trial during the conduct of the study. Dr Bershteyn reported receiving grants from the Bill & Melinda Gates Foundation during the conduct of the study; grants from the NIH and the New York City Department of Health and Mental Hygiene; and personal fees from Gates Ventures outside the submitted work. Dr Landovitz reported serving on the scientific advisory board for Gilead Sciences and Merck Inc; and receiving honoraria for conference presentations from Janssen and Cepheid outside the submitted work. Dr Luk reported receiving grants from the Bill & Melinda Gates Foundation during the conduct of the study. Dr Magaret reported receiving personal fees from Prevencio Inc outside the submitted work. Dr Greninger reported having a contract from Abbott Molecular; receiving grants from Merck; and receiving grants from Gilead outside the submitted work. Dr Wener reported receiving grants from the Bill & Melinda Gates Foundation during the conduct of the study. Dr Celum reported receiving personal fees from Merck and Gilead outside the submitted work. Dr Chu reported receiving grants from the Bill & Melinda Gates Foundation during the conduct of the study; personal fees from Ellume, Merck, the Bill & Melinda Gates Foundation, Pfizer, and Glaxo Smith Kline; grants from Gates Ventures and Sanofi Pasteur; and reagents from from Cepheid and Ellume outside the submitted work. Dr Baeten reported receiving grants from the Bill & Melinda Gates Foundation during the conduct of the study; and being an employee of Gilead Sciences outside the submitted work. Dr Wald reported receiving grants from the Bill & Melinda Gates Foundation during the conduct of the study; nonfinancial support from Merck; personal fees from Aicuris, X-Vax, Crozet, and Auritec; and grants from GSK and Sanofi outside the submitted work. Dr Barnabas reported receiving grants from the NIH and the Bill & Melinda Gates Foundation during the conduct of the study; and nonfinancial support from Regeneron Pharmaceuticals outside the submitted work. Dr Brown reported receiving grants from the Bill & Melinda Gates Foundation during the conduct of the study; and grants from the NIH; and personal fees from Merck outside the submitted work. No other disclosures were reported.

Funding/Support: This study was supported by award INV-016204 from the Bill and Melinda Gates Foundation. Dr Stankiewicz Karita is funded by the Research Supplement from the National Cancer Institute at the NIH (grant R01 CA213130-S) and the Department of Medicine Diversity Academic Development Scholar Award at the University of Washington. Dr Deming is funded by the Infectious Diseases Clinical Research Consortium through the National Institute for Allergy and Infectious Diseases of the NIH, under award number UM1AI148684.

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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