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Control-theoretic immune tradeoffs explain SARS-CoV-2 virulence and transmission variation

Sarma, Anish A. and Sarma, Aartik and Csete, Marie and Lee, Peter P. and Doyle, John C. (2021) Control-theoretic immune tradeoffs explain SARS-CoV-2 virulence and transmission variation. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20210429-095332336

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Abstract

Dramatic variation in SARS-CoV-2 virulence and transmission between hosts has driven the COVID-19 pandemic. The complexity and dynamics of the immune response present a challenge to understanding variation in SARS-CoV-2 infections. To address this challenge, we apply control theory, a framework used to study complex feedback systems, to establish rigorous mathematical bounds on immune responses. Two mechanisms of SARS-CoV-2 biology are sufficient to create extreme variation between hosts: (1) a sparsely expressed host receptor and (2) potent, but not unique, suppression of interferon. The resulting model unifies disparate and unexplained features of the SARS-CoV-2 pandemic, predicts features of future viruses that threaten to cause pandemics, and identifies potential interventions.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2021.04.25.441372DOIDiscussion Paper
ORCID:
AuthorORCID
Sarma, Aartik0000-0002-7508-7345
Csete, Marie0000-0003-4591-0510
Lee, Peter P.0000-0002-2660-4377
Doyle, John C.0000-0002-1828-2486
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. This version posted April 26, 2021.
Group:COVID-19
Record Number:CaltechAUTHORS:20210429-095332336
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210429-095332336
Official Citation:Control-theoretic immune tradeoffs explain SARS-CoV-2 virulence and transmission variation. Anish A. Sarma, Aartik Sarma, Marie Csete, Peter P. Lee, John C. Doyle. bioRxiv 2021.04.25.441372; doi: https://doi.org/10.1101/2021.04.25.441372
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108865
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:29 Apr 2021 18:25
Last Modified:29 Apr 2021 18:25

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