Daily sampling of early SARS-CoV-2 infection reveals substantial heterogeneity in infectiousness

Abstract

The dynamics of SARS-CoV-2 replication and shedding in humans remain poorly understood. We captured the dynamics of infectious virus and viral RNA shedding during acute infection through daily longitudinal sampling of 60 individuals for up to 14 days. By fitting mechanistic models, we directly estimate viral reproduction and clearance rates, and overall infectiousness for each individual. Significant person-to-person variation in infectious virus shedding suggests that individual-level heterogeneity in viral dynamics contributes to superspreading. Viral genome load often peaked days earlier in saliva than in nasal swabs, indicating strong compartmentalization and suggesting that saliva may serve as a superior sampling site for early detection of infection. Viral loads and clearance kinetics of B.1.1.7 and non-B.1.1.7 viruses in nasal swabs were indistinguishable, however B.1.1.7 exhibited a significantly slower pre-peak growth rate in saliva. These results provide a high-resolution portrait of SARS-CoV-2 infection dynamics and implicate individual-level heterogeneity in infectiousness in superspreading.

Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution

“…However, most studies to date base their conclusions on cross sectional sampling of viral genome loads (as measured by RTqPCR), which may not directly translate to infectiousness 6 . In a cohort of longitudinally sampled participants who screened positive for SARS-CoV-2, we previously showed that the relationship between viral genome load and infectious virus load can vary greatly across individuals and over time, making the use of cross-sectional RTqPCR data problematic for estimations of infectiousness 7 . Therefore, longitudinal comparisons of viral genome shedding and infectious virus shedding across tissue compartments between vaccinated and unvaccinated individuals are needed to more accurately assess the effects of vaccination on viral dynamics and transmission potential.…”

“…(C) Same data as in (A) but for newly vaccinated individuals that enrolled < 14 days after first mRNA or J&J vaccine dose. (D) Numbers of days that vaccinated (combined fully and partially vaccinated individuals), newly vaccinated individuals, and unvaccinated individuals (from Ke et al 7 ) tested viral culture positive. ns, p>0.05; * p<0.05; ** p<0.01; *** p<0.001.…”

“…ns, p>0.05; * p<0.05; ** p<0.01; *** p<0.001. (E) Association between the nasal Cn values and the probability of the sample being viral culture positive summarized across the vaccinated individuals, newly vaccinated individuals, and unvaccinated individuals (from Ke et al 7 ). Dots indicate individual viral culture results, 1 being a positive result, and 0 a negative result.…”

Modelling the effectiveness and social costs of daily lateral flow antigen tests versus quarantine in preventing onward transmission of COVID-19 from traced contacts

“…Both models were calibrated to provide realistic incubation period distributions (Supplementary Figure 1), similar distributions of generation time for symptomatic individuals (Supplementary Figure 2) and time from onset of symptoms to transmission (Supplementary Figure 3). The viral load dynamics are assumed to be similar for all viral strains (Kissler, Fauver, Mack, Tai, et al 2021;Ke et al 2021).…”

Incorporating temporal distribution of population-level viral load enables real-time estimation of COVID-19 transmissibility

“…While viral loads can vary across individuals, with some shedding more than others 7 , the mean distribution of viral loads from a group of patients measured around the time of illness onset will tend to have higher values than that of viral loads from a group of patients measured at a later time after infection 8 . Collectively, higher population-level viral loads would correlate with more infected persons being earlier in the course of infection and vice versa 9 .…”