Trajectory of viral load in a prospective population-based cohort with incident SARS-CoV-2 G614 infection

Stankiewicz Karita, H. C.; Dong, T. Q.; Johnston, C.; Neuzil, K. M.; Paasche-Orlow, M. K.; Kissinger, P. J.; Bershteyn, A.; Thorpe, L.; Deming, M.; Kottkamp, A.; Laufer, M.; Landovitz, R.; Luk, A.; Hoffman, R.; Roychoudhury, P.; Magaret, C.; Greninger, A.; Huang, M.; Jerome, K.; Wener, M.; Celum, C. L.; Chu, H. Y.; Baeten, J.; Wald, A.; Barnabas, R. V.; Brown, E. R.

Importance: SARS-CoV-2 viral trajectory has not been well-characterized in documented incident infections. These data will inform SARS-CoV-2 natural history, transmission dynamics, prevention practices, and therapeutic development. Objective: To prospectively characterize early SARS-CoV-2 viral shedding in persons with incident infection. Design: Prospective cohort study. Setting: Secondary data analysis from a multicenter study in the U.S. Participants: The samples derived from a randomized controlled trial of 829 community-based asymptomatic participants recently exposed (<96 hours) to persons with SARS-CoV-2. Participants collected daily mid-turbinate swabs for SARS-CoV-2 detection by polymerase-chain-reaction and symptom diaries for 14-days. Persons with negative swab for SARS-CoV-2 at baseline who developed infection during the study were included in the analysis. Exposure: Laboratory-confirmed SARS-CoV-2 infection. Main outcomes and measures: The observed SARS-CoV-2 viral shedding characteristics were summarized and shedding trajectories were examined using a piece-wise linear mixed-effects modeling. Whole viral genome sequencing was performed on samples with cycle threshold (Ct)<34. Results: Ninety-seven persons (57% women, median age 37-years) developed incident infections during 14-days of follow-up. Two-hundred fifteen sequenced samples were assigned to 15 lineages that belonged to the G614 variant. Forty-two (43%), 18(19%), and 31(32%) participants had viral shedding for 1 day, 2-6 days, and >7 days, with median peak viral load Ct of 38.5, 36.7, and 18.3, respectively. Six (6%) participants had 1-6 days of observed viral shedding with censored duration. The peak average viral load was observed on day 3 of viral shedding. The average Ct value was lower, indicating higher viral load, in persons reporting COVID-19 symptoms than asymptomatic. Using the statistical model, the median time from shedding onset to peak viral load was 1.4 days followed by a median of 9.7 days before clearance. Conclusions and Relevance: Incident SARS-CoV-2 G614 infection resulted in a rapid viral load peak followed by slower decay and positive correlation between peak viral load and shedding duration; duration of shedding was heterogeneous. This longitudinal evaluation of the SARS-CoV-2 G614 variant with frequent molecular testing may serve as a reference for comparing emergent viral lineages to inform clinical trial designs and public health strategies to contain the spread of the virus.