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, Tracy Q. Dong, Christine Johnston, Kathleen M. Neuzil, Michael K. Paasche-Orlow, Patricia J. Kissinger, Anna Bershteyn, Lorna E. Thorpe, Meagan Deming, Angelica Kottkamp, Miriam Laufer, Raphael J. Landovitz, Alfred Luk, Risa Hoffman, Pavitra Roychoudhury, Craig A. Magaret, Alexander L. Greninger, Meei Li Huang, Keith R. Jerome, Mark WenerConnie Celum, Helen Y. Chu, Jared M. Baeten, Anna Wald, Ruanne V. Barnabas, Elizabeth R. Brown

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)E2142796
JournalJAMA network open
Issue number1
StatePublished - Jan 10 2022


  • Adult
  • COVID-19/complications
  • Female
  • Humans
  • Incidence
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Molecular Diagnostic Techniques/methods
  • Polymerase Chain Reaction/methods
  • Prospective Studies
  • RNA, Viral
  • SARS-CoV-2
  • Serologic Tests
  • Severity of Illness Index
  • Viral Load
  • Virus Shedding

ASJC Scopus subject areas

  • General Medicine


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