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bioRxiv · 10.1101/2021.04.25.441372

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

Sarma, A. A.·Sarma, A.·Csete, M.·Lee, P. P.·Doyle, J. C.
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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.

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Sarma, A. A., Sarma, A., Csete, M., Lee, P. P., Doyle, J. C.. 2021-04-26. Control-theoretic immune tradeoffs explain SARS-CoV-2 virulence and transmission variation. https://doi.org/10.1101/2021.04.25.441372

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