ABSTRACT
Understanding the viral dynamics and immunizing antibodies of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for devising better therapeutic and prevention strategies for COVID-19. Here, we present a Bayesian hierarchical model that jointly estimates the diagnostic RNA viral load reflecting genomic materials of SARS-CoV-2, the subgenomic RNAs (sgRNA) viral load reflecting active viral replication, and the rate and timing of seroconversion reflecting presence of antibodies. Our proposed method accounts for the dynamical relationship and correlation structure between the two types of viral load, allows for borrowing of information between viral load and antibody data, and identifies potential correlates of viral load characteristics and propensity for seroconversion. We demonstrate the features of the joint model through application to the COVID-19 PEP study and conduct a cross-validation exercise to illustrate the model's ability to impute the sgRNA viral trajectories for people who only had diagnostic viral load data.
Subject(s)
Coronavirus Infections , COVID-19ABSTRACT
ImportanceSARS-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. ObjectiveTo prospectively characterize early SARS-CoV-2 viral shedding in persons with incident infection. DesignProspective cohort study. SettingSecondary data analysis from a multicenter study in the U.S. ParticipantsThe 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. ExposureLaboratory-confirmed SARS-CoV-2 infection. Main outcomes and measuresThe 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. ResultsNinety-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 RelevanceIncident 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. KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat are the early SARS-CoV-2 G614 viral shedding characteristics in persons with incident infection? FindingsIn this prospective cohort of 97 community-based participants who collected daily mid-turbinate swabs for SARS-CoV-2 detection after recent exposure to SARS-CoV-2, viral trajectory was characterized by a rapid peak followed by slower decay. Peak viral load correlated positively with symptoms. The duration of shedding was heterogeneous. MeaningA detailed description of the SARS-CoV-2 G614 viral shedding trajectory serves as baseline for comparison to new viral variants of concern and inform models for the planning of clinical trials and transmission dynamics to end this pandemic.