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
Authors: 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 Wener, Connie Celum, Helen Y. Chu, Jared M. Baeten, Anna Wald, Ruanne V. Barnabas, Elizabeth R. Brown
Journal: JAMA Network Open (2022)

<h3>Importance</h3> 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. <h3>Objective</h3> 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. <h3>Design, Setting, and Participants</h3> This prospective cohort study was a secondary data analysis of a remotely conducted study that enrolled 829 asymptomatic community-based participants recently exposed (&lt;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. <h3>Exposure</h3> Laboratory-confirmed SARS-CoV-2 infection. <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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). <h3>Conclusions and Relevance</h3> 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.