Hijaking the SARS-CoV-2 Cytokinopathy: Janus Kinase Inhibitors for Moderate to Severe COVID-19

14 Pages Posted: 9 Jun 2020

See all articles by Christine Won

Christine Won

Yale University

William Damsky

Yale University School of Medicine - Department of Dermatology

Inderjit Singh

Yale University

Phillip Joseph

Yale University

Astha Chichra

Yale University

Hannah Oakland

Yale University

Jing Lu

Yale University - Yale New Haven Hospital (YNHH)

Prashanth Vallabhajosyula

Yale University

Amit Bardia

Yale University

Christopher Szabo

Yale University

Alice Wang

Yale University

Kelly Borges

Yale University

Jonathan Koff

Yale University

Carolyn Rochester

Yale University

Brett King

Yale University

Hyung Chun

Yale University

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

Won, Christine and Damsky, William and Singh, Inderjit and Joseph, Phillip and Chichra, Astha and Oakland, Hannah and Lu, Jing and Vallabhajosyula, Prashanth and Bardia, Amit and Szabo, Christopher and Wang, Alice and Borges, Kelly and Koff, Jonathan and Rochester, Carolyn and King, Brett and Chun, Hyung, Hijaking the SARS-CoV-2 Cytokinopathy: Janus Kinase Inhibitors for Moderate to Severe COVID-19 (May 20, 2020). Available at SSRN: https://ssrn.com/abstract=3606658 or http://dx.doi.org/10.2139/ssrn.3606658

Christine Won

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

William Damsky

Yale University School of Medicine - Department of Dermatology ( email )

493 College St
New Haven, CT CT 06520
United States

Inderjit Singh

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

Phillip Joseph

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

Astha Chichra

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

Hannah Oakland

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

Jing Lu

Yale University - Yale New Haven Hospital (YNHH) ( email )

New Haven, CT
United States

Prashanth Vallabhajosyula

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

Amit Bardia

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

Christopher Szabo

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

Alice Wang

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

Kelly Borges

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

Jonathan Koff

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

Carolyn Rochester

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

Brett King

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

Hyung Chun (Contact Author)

Yale University ( email )

493 College St
New Haven, CT CT 06520
United States

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