Hijaking the SARS-CoV-2 Cytokinopathy: Janus Kinase Inhibitors for Moderate to Severe COVID-19
14 Pages Posted: 9 Jun 2020
Date Written: May 20, 2020
Abstract
A subset of patients with SARS-CoV-2 infection develop a cytokine release syndrome (CRS). Strategies to mitigate SARS-CoV-2-induced CRS are urgently needed. Many cytokines that play a role in SARS-CoV-2-induced CRS signal via the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway and are thus inhibited by JAK inhibitors. Compared to IL-6 inhibitors, which are currently being used for SARS-CoV-2-induced CRS, JAK inhibitors offer the potential advantage of simultaneously suppressing the activity of IL-6 plus other implicated cytokines including G-CSF, GM-CSF, IL-2, and IFN-gamma. We discuss the first described use of JAK inhibition in four patients who failed tocilizumab and the rationale for use of JAK inhibitors for CRS in other contexts and their potential in SARS-CoV-2 infection.
Note:
Funding: H.J.C. is supported by research grants from the American Heart Association, NHLBI/NIH and Department of Defense W.D. is supported by a research grant from the Dermatology Foundation A.B. is supported by a research grant from Merck
Declaration of Interest: H.J.C. is a consultant for AstraZeneca, Translate Bio, and ShouTi. BAK is a consultant to and/or has served on advisory boards for Aclaris Therapeutics, Arena Pharmaceuticals, Bristol-Meyers Squibb, Concert Pharmaceuticals Inc, Dermavant Sciences, Eli Lilly and Company, and Pfizer Inc; he is on speaker’s bureau for Pfizer Inc, Regeneron and Sanofi Genzyme W.D. has received research funding from Pfizer and is a consultant for Eli Lilly
Keywords: COVID-19, SARS-CoV-2, JAK inhibitor, ruxolitinib, ECMO, ARDS
Suggested Citation: Suggested Citation