ABSTRACT
Background: Transmission of SARS-CoV-2 is highly heterogeneous, with a small fraction of infected individuals (often referred to as "superspreaders") contributing a disproportionate share of forward transmission. Numerous behavioral and environmental explanations have been offered to explain transmission heterogeneity, but the extent to which the underlying features of the infection process within individual hosts contribute towards the superspreading phenomenon remains unclear. In addition, it is not clear how vaccination would impact on the viral infection dynamics and thus the infectiousness of individuals. Addressing these gaps in knowledge will inform the design of more targeted and effective strategies for controlling community spread. Methods: In a study on UIUC campus (UIUC SHIELD), the dynamics of infectious virus and viral RNA shedding were captured through daily longitudinal sampling of 72 individuals for up to 14 days (60 unvaccinated and 12 vaccinated). We fitted mechanistic models to both viral loads and cell culture positivity data, and directly estimated viral reproduction and clearance rates, and overall infectiousness for each individual. Results: Integrating mathematical models with viral load and cell culture positivity data, we show a substantial level of heterogeneity in infectiousness of individual. In unvaccinated individuals, peak viral loads and clearance kinetics of B.1.1.7 and non-variant of concern viruses were indistinguishable. In vaccinated individuals, the viral dynamics do not follow typical patterns of acute infection dynamics and we estimate that these individuals are much less infectious than unvaccinated individuals. Conclusion: Our work provides a high-resolution portrait of SARS-CoV-2 infection dynamics. Significant person-to-person variation in infectious virus shedding suggests that individual-level heterogeneity in viral dynamics contributes to superspreading. Vaccinated individuals are less infectious than unvaccinated individuals overall.
ABSTRACT
Background: The within-host reproductive number R0 is an important parameter to predict the minimum antiviral efficacy needed to suppress viral infection. However, this parameter has not been well quantified for SARS-CoV-2. This is because accurate estimation of this quantity requires longitudinal viral load measurements during the initial phase of infection, when the virus population expands before the viral load peak;yet, most available measurements are made after the viral load peak. Methods: We constructed viral dynamic models to describe a set of longitudinal viral load data from a study where individuals were tested frequently such that viral loads during the viral expansion phase were measured. We fit multiple models to data from a total of 42 infected individuals (14 symptomatic and 28 asymptomatic) to estimate R0 and used a model linking within-host viral load to the infectiousness of a person to evaluate the infectiousness of asymptomatic individuals compared to symptomatic individuals. Results: We estimated that the within-host R0 is between 8-16 across the 48 individuals. This suggests that antiviral efficacy has to be greater than 95% to suppress virus infection in a majority of individuals. The estimated R0 in asymptomatic individuals is lower than in symptomatic individuals (mean 10.0 vs. 13.8;p-value<0.0001). Our model suggests there exists large heterogeneity in infectiousness among individuals, and asymptomatic individuals may be on average 15% less infectious than symptomatic individuals (p-value=0.02), not considering isolation measures. Conclusion: An antiviral efficacy of 95% or more is needed to suppress viral infection in most infected individuals. Asymptomatic individuals may be slightly less infectious than symptomatic individuals.