@article{3a8f0a35408548bea26f7d23e93a781b,
title = "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 {\textquoteleft}superspreading{\textquoteright}. 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.",
keywords = "Infectious-disease diagnostics, Stochastic modelling, SARS-CoV-2, COVID-19",
author = "Ruian Ke and Martinez, {Pamela P.} and Smith, {Rebecca L.} and Gibson, {Laura L.} and Agha Mirza and Madison Conte and Nicholas Gallagher and Luo, {Chun Huai} and Junko Jarrett and Ruifeng Zhou and Abigail Conte and Tongyu Liu and Mireille Farjo and Walden, {Kimberly K. O.} and Gloria Rendon and Fields, {Christopher J.} and Leyi Wang and Richard Fredrickson and Edmonson, {Darci C.} and Baughman, {Melinda E.} and Chiu, {Karen K.} and Hannah Choi and Scardina, {Kevin R.} and Shannon Bradley and Gloss, {Stacy L.} and Crystal Reinhart and Jagadeesh Yedetore and Jessica Quicksall and Owens, {Alyssa N.} and John Broach and Bruce Barton and Peter Lazar and Heetderks, {William J.} and Robinson, {Matthew L.} and Mostafa, {Heba H.} and Manabe, {Yukari C.} and Andrew Pekosz and McManus, {David D.} and Brooke, {Christopher B.}",
note = "We thank S. Ahmed, C. Bell, N. Bouton, C. Brennen, J. Brown, C. Buie, E. Cler, G. Cole, T. Coleman, A. Dunnett, L. Engels, S. Feher, K. Fox, L. Freeman, Y. Gonzalez, M. Harris, D. Henness, D. Hiser, A. Hussain, D. Jackson, J. Jarrett, M. Jenkins, K. Kalonji, S. Kanku, S. Krauklis, M. Krouse, E. Leshoure, J. Lewis, M. Li, A. Lopez, G. Lopez, E. Luna, C. H. Luo, C. Mackey, Sk. McLain, Y. B. Melesse, M. O{\textquoteright}Donnell, S. Pflugmacher, D. Piatt, S. Pierce, G. Quitanilla, A. Samad, M. Scroggins, M. Settles, M. Sinn, P. Varney, E. Vlach, R. Williams-Chatman and T. Young for their efforts supporting recruitment, enrolment, logistics and/or sample collection and processing. We thank J. Olgin, N. Peyser and X. Butcher for assistance with the Eureka platform, M. Lore for assistance with REDcap, M. Loots for assistance with administration, G. Snyder for assistance in development of study protocols and logistics and E. Iturriaga and J. Chen for study protocol development. We thank A. Neumann for helpful input and suggestions for improving the analyses. Finally we thank A. Hernandez and C. Wright of the DNA Services Lab within the Roy J. Carver Biotechnology Center for assistance in establishment of a SARS-CoV-2 genomic sequencing protocol. Vero-TMPRSS2 cells were provided by the National Institute of Infectious Diseases, Japan. Sofia 2 devices and associated supplies were provided to Carle Foundation Hospital by Quidel, although Quidel played no role in the design of the study or the interpretation or presentation of the data. This work was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health (no. 3U54HL143541-02S2) through the RADx-Tech programme, to D.D.M., L.L.G. and C.B.B. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Institute of Biomedical Imaging and Bioengineering, the National Heart, Lung, and Blood Institute, the National Institutes of Health or the US Department of Health and Human Services. R.K. and C.B.B. were further supported by the Defense Advanced Research Projects Agency INTERCEPT programme through contract nos. R-00676-19-0 (to R.K.) and W911NF-17-2-0034 (to C.B.B.).",
year = "2022",
month = may,
doi = "10.1101/2021.07.12.21260208",
language = "English (US)",
volume = "7",
pages = "640--652",
journal = "Nature Microbiology",
issn = "2058-5276",
publisher = "Nature Publishing Group",
number = "5",
}