In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness

Ke, Ruian; Zitzmann, Carolin; Ho, David D.; Ribeiro, Ruy M.; Perelson, Alan S.

doi:10.1073/pnas.2111477118

In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness

Journal Article · Wed Dec 01 23:00:00 EST 2021 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.2111477118· OSTI ID:1833729

^[1]; Zitzmann, Carolin ^[2]; ^[3]; ^[2]; ^[1]

Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545,, New Mexico Consortium, Los Alamos, NM 87544,
Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545,
Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032

Significance

Quantifying the kinetics of SARS-CoV-2 infection and individual infectiousness is important for understanding SARS-CoV-2 transmission and evaluating intervention strategies. Here, we developed 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 as 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.

View Journal Article

Sponsoring Organization:: USDOE

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 1833729

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 49 Vol. 118; ISSN 0027-8424

Publisher:: Proceedings of the National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

References (46)

Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset Cheng, Hao-Yuan; Jian, Shu-Wan; Liu, Ding-Ping JAMA Internal Medicine, Vol. 180, Issue 9 https://doi.org/10.1001/jamainternmed.2020.2020	journal	September 2020
Assessment of SARS-CoV-2 Screening Strategies to Permit the Safe Reopening of College Campuses in the United States Paltiel, A. David; Zheng, Amy; Walensky, Rochelle P. JAMA Network Open, Vol. 3, Issue 7 https://doi.org/10.1001/jamanetworkopen.2020.16818	journal	July 2020
SARS-CoV-2 Transmission From People Without COVID-19 Symptoms Johansson, Michael A.; Quandelacy, Talia M.; Kada, Sarah JAMA Network Open, Vol. 4, Issue 1 https://doi.org/10.1001/jamanetworkopen.2020.35057	journal	January 2021
Timing of Antiviral Treatment Initiation is Critical to Reduce SARS‐CoV‐2 Viral Load Gonçalves, Antonio; Bertrand, Julie; Ke, Ruian CPT: Pharmacometrics & Systems Pharmacology, Vol. 9, Issue 9 https://doi.org/10.1002/psp4.12543	journal	August 2020
Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series Böhmer, Merle M.; Buchholz, Udo; Corman, Victor M. The Lancet Infectious Diseases, Vol. 20, Issue 8 https://doi.org/10.1016/S1473-3099(20)30314-5	journal	August 2020
Pediatric Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Clinical Presentation, Infectivity, and Immune Responses Yonker, Lael M.; Neilan, Anne M.; Bartsch, Yannic The Journal of Pediatrics, Vol. 227 https://doi.org/10.1016/j.jpeds.2020.08.037	journal	December 2020
Estimating the reproductive number R0 of SARS-CoV-2 in the United States and eight European countries and implications for vaccination Ke, Ruian; Romero-Severson, Ethan; Sanche, Steven Journal of Theoretical Biology, Vol. 517 https://doi.org/10.1016/j.jtbi.2021.110621	journal	May 2021
Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19) van Kampen, Jeroen J. A.; van de Vijver, David A. M. C.; Fraaij, Pieter L. A. Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-020-20568-4	journal	January 2021
Virological assessment of hospitalized patients with COVID-2019 Wölfel, Roman; Corman, Victor M.; Guggemos, Wolfgang Nature, Vol. 581, Issue 7809 https://doi.org/10.1038/s41586-020-2196-x	journal	April 2020
Temporal dynamics in viral shedding and transmissibility of COVID-19 He, Xi; Lau, Eric H. Y.; Wu, Peng Nature Medicine, Vol. 26, Issue 5 https://doi.org/10.1038/s41591-020-0869-5	journal	April 2020
Initial report of decreased SARS-CoV-2 viral load after inoculation with the BNT162b2 vaccine Levine-Tiefenbrun, Matan; Yelin, Idan; Katz, Rachel Nature Medicine, Vol. 27, Issue 5 https://doi.org/10.1038/s41591-021-01316-7	journal	March 2021
SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients Zou, Lirong; Ruan, Feng; Huang, Mingxing New England Journal of Medicine, Vol. 382, Issue 12 https://doi.org/10.1056/NEJMc2001737	journal	March 2020
Natural History of Asymptomatic SARS-CoV-2 Infection Sakurai, Aki; Sasaki, Toshiharu; Kato, Shigeo New England Journal of Medicine, Vol. 383, Issue 9 https://doi.org/10.1056/NEJMc2013020	journal	August 2020
Asymptomatic Transmission, the Achilles’ Heel of Current Strategies to Control Covid-19 Gandhi, Monica; Yokoe, Deborah S.; Havlir, Diane V. New England Journal of Medicine, Vol. 382, Issue 22 https://doi.org/10.1056/NEJMe2009758	journal	May 2020
A Novel Coronavirus from Patients with Pneumonia in China, 2019 Zhu, Na; Zhang, Dingyu; Wang, Wenling New England Journal of Medicine, Vol. 382, Issue 8 https://doi.org/10.1056/NEJMoa2001017	journal	February 2020
Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility Arons, Melissa M.; Hatfield, Kelly M.; Reddy, Sujan C. New England Journal of Medicine, Vol. 382, Issue 22 https://doi.org/10.1056/NEJMoa2008457	journal	May 2020
Rethinking Covid-19 Test Sensitivity — A Strategy for Containment Mina, Michael J.; Parker, Roy; Larremore, Daniel B. New England Journal of Medicine, Vol. 383, Issue 22 https://doi.org/10.1056/NEJMp2025631	journal	November 2020
Variation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesis Fraser, C.; Hollingsworth, T. D.; Chapman, R. Proceedings of the National Academy of Sciences, Vol. 104, Issue 44 https://doi.org/10.1073/pnas.0708559104	journal	October 2007
The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission Stadnytskyi, Valentyn; Bax, Christina E.; Bax, Adriaan Proceedings of the National Academy of Sciences, Vol. 117, Issue 22 https://doi.org/10.1073/pnas.2006874117	journal	May 2020
Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort Néant, Nadège; Lingas, Guillaume; Le Hingrat, Quentin Proceedings of the National Academy of Sciences, Vol. 118, Issue 8 https://doi.org/10.1073/pnas.2017962118	journal	February 2021
Correlation Between 3790 Quantitative Polymerase Chain Reaction–Positives Samples and Positive Cell Cultures, Including 1941 Severe Acute Respiratory Syndrome Coronavirus 2 Isolates Jaafar, Rita; Aherfi, Sarah; Wurtz, Nathalie Clinical Infectious Diseases, Vol. 72, Issue 11 https://doi.org/10.1093/cid/ciaa1491	journal	September 2020
Distribution of Transmission Potential During Nonsevere COVID-19 Illness Shrestha, Nabin K.; Marco Canosa, Francisco; Nowacki, Amy S. Clinical Infectious Diseases, Vol. 71, Issue 11 https://doi.org/10.1093/cid/ciaa886	journal	June 2020
Reconciling early-outbreak estimates of the basic reproductive number and its uncertainty: framework and applications to the novel coronavirus (SARS-CoV-2) outbreak Park, Sang Woo; Bolker, Benjamin M.; Champredon, David Journal of The Royal Society Interface, Vol. 17, Issue 168 https://doi.org/10.1098/rsif.2020.0144	journal	July 2020
Crossing the scale from within-host infection dynamics to between-host transmission fitness: a discussion of current assumptions and knowledge Handel, Andreas; Rohani, Pejman Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 370, Issue 1675 https://doi.org/10.1098/rstb.2014.0302	journal	August 2015
Mathematical modeling of within-host Zika virus dynamics Best, Katharine; Perelson, Alan S. Immunological Reviews, Vol. 285, Issue 1 https://doi.org/10.1111/imr.12687	journal	August 2018
Review and comparison between the WellsâRiley and dose-response approaches to risk assessment of infectious respiratory diseases Sze To, G. N.; Chao, C. Y. H. Indoor Air, Vol. 20, Issue 1 https://doi.org/10.1111/j.1600-0668.2009.00621.x	journal	February 2010
Potency and timing of antiviral therapy as determinants of duration of SARS-CoV-2 shedding and intensity of inflammatory response Goyal, Ashish; Cardozo-Ojeda, E. Fabian; Schiffer, Joshua T. Science Advances, Vol. 6, Issue 47 https://doi.org/10.1126/sciadv.abc7112	journal	October 2020
Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening Larremore, Daniel B.; Wilder, Bryan; Lester, Evan Science Advances, Vol. 7, Issue 1 https://doi.org/10.1126/sciadv.abd5393	journal	November 2020
Type 1 Interferons and the Virus-Host Relationship: A Lesson in Detente Garcia-Sastre, A. Science, Vol. 312, Issue 5775 https://doi.org/10.1126/science.1125676	journal	May 2006
Serial interval of SARS-CoV-2 was shortened over time by nonpharmaceutical interventions Ali, Sheikh Taslim; Wang, Lin; Lau, Eric H. Y. Science, Vol. 369, Issue 6507 https://doi.org/10.1126/science.abc9004	journal	July 2020
Estimating infectiousness throughout SARS-CoV-2 infection course Jones, Terry C.; Biele, Guido; Mühlemann, Barbara Science, Vol. 373, Issue 6551 https://doi.org/10.1126/science.abi5273	journal	July 2021
Antiviral Actions of Interferons Samuel, C. E. Clinical Microbiology Reviews, Vol. 14, Issue 4 https://doi.org/10.1128/CMR.14.4.778-809.2001	journal	October 2001
Kinetics of Influenza A Virus Infection in Humans Baccam, P.; Beauchemin, C.; Macken, C. A. Journal of Virology, Vol. 80, Issue 15 https://doi.org/10.1128/JVI.01623-05	journal	July 2006
Dynamics of Influenza Virus Infection and Pathology Saenz, R. A.; Quinlivan, M.; Elton, D. Journal of Virology, Vol. 84, Issue 8 https://doi.org/10.1128/JVI.02078-09	journal	February 2010
Viral dynamics of acute SARS-CoV-2 infection and applications to diagnostic and public health strategies Kissler, Stephen M.; Fauver, Joseph R.; Mack, Christina PLOS Biology, Vol. 19, Issue 7 https://doi.org/10.1371/journal.pbio.3001333	journal	July 2021
Neuraminidase Inhibitor Resistance in Influenza: Assessing the Danger of Its Generation and Spread Handel, Andreas; Longini, Ira M.; Antia, Rustom PLoS Computational Biology, Vol. 3, Issue 12 https://doi.org/10.1371/journal.pcbi.0030240	journal	December 2007
Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses Pawelek, Kasia A.; Huynh, Giao T.; Quinlivan, Michelle PLoS Computational Biology, Vol. 8, Issue 6 https://doi.org/10.1371/journal.pcbi.1002588	journal	June 2012
Success of prophylactic antiviral therapy for SARS-CoV-2: Predicted critical efficacies and impact of different drug-specific mechanisms of action Czuppon, Peter; Débarre, Florence; Gonçalves, Antonio PLOS Computational Biology, Vol. 17, Issue 3 https://doi.org/10.1371/journal.pcbi.1008752	journal	March 2021
Social Contacts and Mixing Patterns Relevant to the Spread of Infectious Diseases Mossong, Joël; Hens, Niel; Jit, Mark PLoS Medicine, Vol. 5, Issue 3 https://doi.org/10.1371/journal.pmed.0050074	journal	March 2008
Secondary Transmission of Coronavirus Disease from Presymptomatic Persons, China Zhang, Weiwei; Cheng, Weibin; Luo, Lei Emerging Infectious Diseases, Vol. 26, Issue 8 https://doi.org/10.3201/eid2608.201142	journal	August 2020
SARS-CoV-2 Virus Culture and Subgenomic RNA for Respiratory Specimens from Patients with Mild Coronavirus Disease Perera, Ranawaka A. P. M.; Tso, Eugene; Tsang, Owen T. Y. Emerging Infectious Diseases, Vol. 26, Issue 11 https://doi.org/10.3201/eid2611.203219	journal	November 2020
The Comparative Clinical Performance of Four SARS-CoV-2 Rapid Antigen Tests and Their Correlation to Infectivity In Vitro Kohmer, Niko; Toptan, Tuna; Pallas, Christiane Journal of Clinical Medicine, Vol. 10, Issue 2 https://doi.org/10.3390/jcm10020328	journal	January 2021
Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure Kucirka, Lauren M.; Lauer, Stephen A.; Laeyendecker, Oliver Annals of Internal Medicine, Vol. 173, Issue 4 https://doi.org/10.7326/M20-1495	journal	August 2020
Contact Settings and Risk for Transmission in 3410 Close Contacts of Patients With COVID-19 in Guangzhou, China: A Prospective Cohort Study Luo, Lei; Liu, Dan; Liao, Xinlong Annals of Internal Medicine, Vol. 173, Issue 11 https://doi.org/10.7326/M20-2671	journal	December 2020
Viral load and contact heterogeneity predict SARS-CoV-2 transmission and super-spreading events Goyal, Ashish; Reeves, Daniel B.; Cardozo-Ojeda, E. Fabian eLife, Vol. 10 https://doi.org/10.7554/eLife.63537	journal	February 2021
Quantifying the relationship between SARS-CoV-2 viral load and infectiousness Marc, Aurélien; Kerioui, Marion; Blanquart, François eLife, Vol. 10 https://doi.org/10.7554/eLife.69302	journal	September 2021

Similar Records

Modeling Within-Host Dynamics of SARS-CoV-2 Infection: A Case Study in Ferrets

Journal Article · Wed Aug 18 00:00:00 EDT 2021 · Viruses · OSTI ID:1825455

The kinetics of SARS-CoV-2 infection based on a human challenge study

Journal Article · Wed Nov 06 23:00:00 EST 2024 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:2476565

In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness

Citation Formats

References (46)

Similar Records

Related Subjects