Dataset Information

Daily longitudinal sampling of 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 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 explained simply 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.

SUBMITTER: Ke R

PROVIDER: S-EPMC9084242 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Ke Ruian R Martinez Pamela P PP Smith Rebecca L RL Gibson Laura L LL Mirza Agha A Conte Madison M Gallagher Nicholas N Luo Chun Huai CH Jarrett Junko J Zhou Ruifeng R Conte Abigail A Liu Tongyu T Farjo Mireille M Walden Kimberly K O KKO Rendon Gloria G Fields Christopher J CJ Wang Leyi L Fredrickson Richard R Edmonson Darci C DC Baughman Melinda E ME Chiu Karen K KK Choi Hannah H Scardina Kevin R KR Bradley Shannon S Gloss Stacy L SL Reinhart Crystal C Yedetore Jagadeesh J Quicksall Jessica J Owens Alyssa N AN Broach John J Barton Bruce B Lazar Peter P Heetderks William J WJ Robinson Matthew L ML Mostafa Heba H HH Manabe Yukari C YC Pekosz Andrew A McManus David D DD Brooke Christopher B CB

Nature microbiology 20220428 5

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 heterogeneit ...[more]

PMID: 35484231

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Project description:The within-host viral kinetics of SARS-CoV-2 infection and how they relate to a person's infectiousness are not well understood. This limits our ability to quantify the impact of interventions on viral transmission. Here, we develop data-driven viral dynamic models of SARS-CoV-2 infection and estimate key within-host parameters such as the infected cell half-life and the within-host reproductive number. We then develop a model linking VL to infectiousness, showing that a person's infectiousness increases sub-linearly with VL. We show that the logarithm of the VL in the upper respiratory tract (URT) is a better surrogate of infectiousness than the VL itself. Using data on VL and the predicted infectiousness, we further incorporated data on antigen and reverse transcription polymerase chain reaction (RT-PCR) tests and compared their usefulness in detecting infection and preventing transmission. We found that RT-PCR tests perform better than antigen tests assuming equal testing frequency; however, more frequent antigen testing may perform equally well with RT-PCR tests at a lower cost, but with many more false-negative tests. Overall, our models provide a quantitative framework for inferring the impact of therapeutics and vaccines that lower VL on the infectiousness of individuals and for evaluating rapid testing strategies. Quantifying the kinetics of SARS-CoV-2 infection and individual infectiousness is key to quantitatively understanding SARS-CoV-2 transmission and evaluating intervention strategies. Here we developed data-driven within-host models of SARS-CoV-2 infection and by fitting them to clinical data we estimated key within-host viral dynamic parameters. We also developed a mechanistic model for viral transmission and show that the logarithm of the viral load in the upper respiratory tract serves an appropriate surrogate for a person's infectiousness. Using data on how viral load changes during infection, we further evaluated the effectiveness of PCR and antigen-based testing strategies for averting transmission and identifying infected individuals.

Dataset Information

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

Publications

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

Similar Datasets

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