Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2022 Jan 4;5(1):e2142796.
doi: 10.1001/jamanetworkopen.2021.42796.

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

Helen C Stankiewicz Karita  1 , Tracy Q Dong  2 , Christine Johnston  1   2   3 , Kathleen M Neuzil  4 , Michael K Paasche-Orlow  5   6 , Patricia J Kissinger  7 , Anna Bershteyn  8 , Lorna E Thorpe  8 , Meagan Deming  4 , Angelica Kottkamp  9 , Miriam Laufer  4   10 , Raphael J Landovitz  11 , Alfred Luk  12 , Risa Hoffman  10 , Pavitra Roychoudhury  2   3 , Craig A Magaret  2   3 , Alexander L Greninger  2   3 , Meei-Li Huang  2 , Keith R Jerome  2   3 , Mark Wener  3   13 , Connie Celum  1   14   15 , Helen Y Chu  1   14   15 , Jared M Baeten  1   14   15 , Anna Wald  1   2   3   15 , Ruanne V Barnabas  1   14   15 , Elizabeth R Brown  2   16   17
Affiliations
Randomized Controlled Trial

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

Helen C Stankiewicz Karita et al. JAMA Netw Open. .

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.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.. Observed Shedding Duration and Peak Viral Load Among 97 Participants With Incident SARS-CoV-2 Infection (Incident Infection Cohort)
We grouped the participants according to the observed duration of shedding in days. Each dot indicates a participant’s observed peak viral RNA load, defined as the minimum mean cycle threshold (Ct) value measured during study follow-up. The horizontal line segments indicate the median peak viral load in each shedding duration group, and the shaded areas indicate the 95% CIs around the median values, calculated using the Kaplan-Meier method that accounted for censoring and clustering within households.
Figure 2.
Figure 2.. Mean SARS-CoV-2 Viral RNA Load Cycle Threshold (Ct) Values by Day of Viral Shedding During the 14-Day Study Follow-up
The shaded areas indicate the pointwise 95% CIs of the mean viral RNA load. The sample sizes for the mean viral load calculations are presented in the table. Centers for Disease Control and Prevention clinical criteria were used to ascertain symptomatic COVID-19 cases. Fewer than 16 asymptomatic persons were used to calculate the mean viral load after day 7 of viral shedding.
Figure 3.
Figure 3.. Model-Estimated Population-Level Viral RNA Load Trajectories in Cycle Threshold (Ct) Values for Participants Infected With SARS-CoV-2 Who Had at Least 2 Positive Swab Samples During Study Follow-up
The estimated time from onset of shedding to presentation of mild symptoms or moderate or severe symptoms is indicated by the vertical dashed lines, with the shaded areas indicating 95% credible intervals of the associated curve and its bounds.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. World Health Organization . COVID-19 vaccines. Accessed June 25, 2021. https://www.who.int/teams/regulation-prequalification/eul/covid-19
    1. Ritchie H, Mathieu E, Rodés-Guirao L, et al. . Coronavirus Pandemic (COVID-19). Our World in Data. Accessed June 25, 2021. https://ourworldindata.org/coronavirus
    1. Volz E, Mishra S, Chand M, et al. ; COVID-19 Genomics UK (COG-UK) consortium . Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England. Nature. 2021;593(7858):266-269. doi:10.1038/s41586-021-03470-x - DOI - PubMed
    1. Tegally H, Wilkinson E, Giovanetti M, et al. . Detection of a SARS-CoV-2 variant of concern in South Africa. Nature. 2021;592(7854):438-443. doi:10.1038/s41586-021-03402-9 - DOI - PubMed
    1. Davies NG, Abbott S, Barnard RC, et al. ; CMMID COVID-19 Working Group; COVID-19 Genomics UK (COG-UK) Consortium . Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science. 2021;372(6538):eabg3055. doi:10.1126/science.abg3055 - DOI - PMC - PubMed

Publication types