Preprint Review Version 1 This version is not peer-reviewed

Preventing Mortality in COVID-19 Patients: Which Cytokine to Target in a Raging Storm?

Version 1 : Received: 13 June 2020 / Approved: 14 June 2020 / Online: 14 June 2020 (15:44:38 CEST)

How to cite: Lu, L.; Zhang, H.; Zhan, M.; Jiang, J.; Yin, H.; Dauphars, D.; Li, S.; Li, Y.; He, Y. Preventing Mortality in COVID-19 Patients: Which Cytokine to Target in a Raging Storm?. Preprints 2020, 2020060183 (doi: 10.20944/preprints202006.0183.v1). Lu, L.; Zhang, H.; Zhan, M.; Jiang, J.; Yin, H.; Dauphars, D.; Li, S.; Li, Y.; He, Y. Preventing Mortality in COVID-19 Patients: Which Cytokine to Target in a Raging Storm?. Preprints 2020, 2020060183 (doi: 10.20944/preprints202006.0183.v1).

Abstract

Coronavirus disease 2019 (COVID-19) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous morbidity and mortality worldwide. A major underlying cause of COVID-19 mortality is a hyperinflammatory cytokine storm in severe/critically ill patients. Although many clinical trials are testing the efficacy of targeting inflammatory cytokines/chemokines in COVID-19 patients, the critical inflammatory mediator initiating COVID-19 patient death is undefined. Here we suggest that the immunopathological pathway leading to COVID-19 mortality can be divided into three stages with distinct clinical features that can be used to guide therapeutic strategies. Our interpretation of the recently published clinical trials from COVID-19 patients suggests that the clinical efficacy in preventing COVID-19 mortality using IL-1 blockade is subjected to notable caveats, while that for IL-6 blockade is suboptimal. We discuss critical factors in determining appropriate inflammatory cytokine/chemokine targets, timing, and combination of treatments to prevent COVID-19 mortality.

Subject Areas

COVID-19; SARS-CoV-2; mortality; cytokine storm; cytokine release syndrome; chemokine; inflammation; immunopathology; IL-6; IL-1; CCL2; CCL5

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