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

By Anish A Sarma, Aartik Sarma, Marie Csete, Peter P Lee, John C. Doyle

Posted 26 Apr 2021
bioRxiv DOI: 10.1101/2021.04.25.441372

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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