Daily Sampling of Early SARS-CoV-2 Infection Reveals Substantial Heterogeneity in Infectiousness

Ruian Ke; Pamela P Martinez; Rebecca L Smith; Laura L Gibson; Agha Mirza; Madison Conte; Nicholas Gallagher; Chun Huai Luo; Junko Jarrett; Abigail Conte; Tongyu Liu; Mireille Farjo; Kimberly K O Walden; Gloria Rendon; Christopher J Fields; Leyi Wang; Richard Fredrickson; Darci C Edmonson; Melinda E Baughman; Karen K Chiu; Hannah Choi; Kevin R Scardina; Shannon Bradley; Stacy L Gloss; Crystal Reinhart; Jagadeesh Yedetore; Jessica Quicksall; Alyssa N Owens; John Broach; Bruce Barton; Peter Lazar; William J Heetderks; Matthew L Robinson; Heba H Mostafa; Yukari C Manabe; Andrew Pekosz; David D McManus; Christopher B Brooke

doi:10.1101/2021.07.12.21260208

Daily Sampling of Early SARS-CoV-2 Infection Reveals Substantial Heterogeneity in Infectiousness

Ruian Ke, Pamela P Martinez, Rebecca L Smith, Laura L Gibson, Agha Mirza, Madison Conte, Nicholas Gallagher, Chun Huai Luo, Junko Jarrett, Abigail Conte, Tongyu Liu, Mireille Farjo, Kimberly K O Walden, Gloria Rendon, Christopher J Fields, Leyi Wang, Richard Fredrickson, Darci C Edmonson, Melinda E Baughman, Karen K ChiuHannah Choi, Kevin R Scardina, Shannon Bradley, Stacy L Gloss, Crystal Reinhart, Jagadeesh Yedetore, Jessica Quicksall, Alyssa N Owens, John Broach, Bruce Barton, Peter Lazar, William J Heetderks, Matthew L Robinson, Heba H Mostafa, Yukari C Manabe, Andrew Pekosz, David D McManus, Christopher B Brooke

Research output: Working paper › Preprint

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.

Original language	English (US)
Publisher	Cold Spring Harbor Laboratory Press
Number of pages	23
DOIs	https://doi.org/10.1101/2021.07.12.21260208
State	In preparation - Jul 12 2021

Publication series

Name	medRxiv

Keywords

COVID-19
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Online availability

10.1101/2021.07.12.21260208

Cite this

Ke, R., Martinez, P. P., Smith, R. L., Gibson, L. L., Mirza, A., Conte, M., Gallagher, N., Luo, C. H., Jarrett, J., Conte, A., Liu, T., Farjo, M., Walden, K. K. O., Rendon, G., Fields, C. J., Wang, L., Fredrickson, R., Edmonson, D. C., Baughman, M. E., ... Brooke, C. B. (2021). Daily Sampling of Early SARS-CoV-2 Infection Reveals Substantial Heterogeneity in Infectiousness. (medRxiv). Cold Spring Harbor Laboratory Press. https://doi.org/10.1101/2021.07.12.21260208

Ke, R, Martinez, PP , Smith, RL, Gibson, LL, Mirza, A, Conte, M, Gallagher, N, Luo, CH, Jarrett, J, Conte, A, Liu, T, Farjo, M, Walden, KKO, Rendon, G, Fields, CJ , Wang, L, Fredrickson, R, Edmonson, DC, Baughman, ME, Chiu, KK, Choi, H, Scardina, KR, Bradley, S, Gloss, SL, Reinhart, C, Yedetore, J, Quicksall, J, Owens, AN, Broach, J, Barton, B, Lazar, P, Heetderks, WJ, Robinson, ML, Mostafa, HH, Manabe, YC, Pekosz, A, McManus, DD & Brooke, CB 2021 'Daily Sampling of Early SARS-CoV-2 Infection Reveals Substantial Heterogeneity in Infectiousness' medRxiv, Cold Spring Harbor Laboratory Press. https://doi.org/10.1101/2021.07.12.21260208

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title = "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.",

keywords = "COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)",

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 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 = "This work was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [3U54HL143541-02S2] through the RADx-Tech program. 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 U.S. Department of Health and Human Services.",

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AU - Smith, Rebecca L

AU - Gibson, Laura L

AU - Mirza, Agha

AU - Conte, Madison

AU - Gallagher, Nicholas

AU - Luo, Chun Huai

AU - Jarrett, Junko

AU - Conte, Abigail

AU - Liu, Tongyu

AU - Farjo, Mireille

AU - Walden, Kimberly K O

AU - Rendon, Gloria

AU - Fields, Christopher J

AU - Wang, Leyi

AU - Fredrickson, Richard

AU - Edmonson, Darci C

AU - Baughman, Melinda E

AU - Chiu, Karen K

AU - Choi, Hannah

AU - Scardina, Kevin R

AU - Bradley, Shannon

AU - Gloss, Stacy L

AU - Reinhart, Crystal

AU - Yedetore, Jagadeesh

AU - Quicksall, Jessica

AU - Owens, Alyssa N

AU - Broach, John

AU - Barton, Bruce

AU - Lazar, Peter

AU - Heetderks, William J

AU - Robinson, Matthew L

AU - Mostafa, Heba H

AU - Manabe, Yukari C

AU - Pekosz, Andrew

AU - McManus, David D

AU - Brooke, Christopher B

N1 - This work was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [3U54HL143541-02S2] through the RADx-Tech program. 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 U.S. Department of Health and Human Services.

PY - 2021/7/12

Y1 - 2021/7/12

N2 - 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.

AB - 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.

KW - COVID-19

KW - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

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DO - 10.1101/2021.07.12.21260208

M3 - Preprint

C2 - 34282424

T3 - medRxiv

BT - Daily Sampling of Early SARS-CoV-2 Infection Reveals Substantial Heterogeneity in Infectiousness

PB - Cold Spring Harbor Laboratory Press

ER -

Daily Sampling of Early SARS-CoV-2 Infection Reveals Substantial Heterogeneity in Infectiousness

Abstract

Publication series

Keywords

Online availability

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Cite this