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 estimated viral expansion 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 loads often peaked days earlier in saliva than in nasal swabs, indicating strong tissue compartmentalization and suggesting that saliva may serve as a superior sampling site for early detection of infection. Viral loads and clearance kinetics of Alpha (B.1.1.7) and previously circulating non-variant of concern viruses were mostly indistinguishable, indicating that the enhanced transmissibility of this variant cannot be simply explained by higher viral loads or delayed clearance. These results provide a high-resolution portrait of SARS-CoV-2 infection dynamics and implicate individual-level heterogeneity in infectiousness in superspreading.

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Background Serial screening is critical for restricting spread of SARS-CoV-2 by facilitating the timely identification of infected individuals to interrupt transmission chains. The variation in sensitivity of different diagnostic tests at different stages of infection has not been well documented. Methods This is a longitudinal study of 43 adults newly infected with SARS-CoV-2. All participants provided daily samples for saliva and nasal swab RTqPCR, Quidel SARS Sofia antigen FIA, and live virus culture. Results We show that both RTqPCR and the Quidel SARS Sofia antigen FIA peak in sensitivity during the period in which live virus is detected in nasal swabs, but the sensitivity of RTqPCR tests rises more rapidly prior to this period. We also estimate the sensitivities of RTqPCR and antigen tests as a function of testing frequency. Conclusions RTqPCR tests are more effective than antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (given timely results reporting). All tests showed >98% sensitivity for identifying infected individuals if used at least every three days. Daily screening using antigen tests can achieve ~90% sensitivity for identifying infected individuals while they are viral culture positive.