key: cord-0946419-fynxciwg
authors: Peterson, Danielle; Damsky, William; King, Brett
title: Calm before the storm: understanding the role of JAK inhibitors in COVID-19
date: 2020-04-25
journal: J Am Acad Dermatol
DOI: 10.1016/j.jaad.2020.04.097
sha: 7bea0dd1b3112fbe7be23439955f7d0c5271b451
doc_id: 946419
cord_uid: fynxciwg

nan

inhibit proteins potentially involved in SARS-CoV-2 entry into cells. 1 Not only is that work theoretical, 46 that this potential inhibition might provide clinical benefit to patients infected with SARS-CoV-2 is even 47 further unknown. Also, based on in vitro assays, the concentration of baricitinib needed to inhibit 48 AAK1 and clathrin-mediated endocytosis would likely require doses far above the FDA approved dose 49 of baricitinib 2mg daily. 2 Lastly, the theoretical effect against viral endocytosis only applies to 50 baricitinib; this is not a known property of other JAK inhibitors, including upadacitinib. Based on these 51 considerations, we believe there is insufficient evidence to recommend continuing JAK inhibitors in 52 patients who are acutely infected with SARS-CoV-2. 53 54 Napolitano et al suggest that baricitinib and upadacitinib might be useful in treating the cytokine 55 release syndrome (CRS) that can occur in SARS-CoV-2 infection. We strongly agree that there may be a 56 role for JAK inhibitors in treating SARS-CoV-2-associated CRS. However, it is important to note that this 57 is typically a late manifestation of disease that occurs only in a subset of patients. Furthermore, there is 58 evidence in both rhesus macaques and mice infected with the original SARS virus, SARS-CoV, that a 59 suboptimal early anti-viral type I interferon response may predispose to this late manifestation. 3,4 JAK 60 cytokines including IL-2, interferon gamma, GM-CSF, and G-CSF. Important to note is that the 64 theoretical benefit of JAK inhibitors in this setting is not limited to upadacitinib and baricitinib but also 65 applies to other JAK inhibitors including ruxolitinib and tofacitinib. We and others are undertaking 66 clinical trials to evaluate JAK inhibitors for SARS-CoV-2-associated CRS, and it will be interesting to see 67 what they show. 68

In summary, we believe there is insufficient evidence to recommend that JAK inhibitors be continued in 70 all patients taking these medications who are acutely infected with SARS-CoV-2. While JAK inhibitors 71 may prove useful in the treatment of SARS-CoV-2-associated CRS, this is a separate consideration of a 72 relatively uncommon manifestation of this viral infection that occurs late in disease course. 73 74 75 76

Baricitinib as potential treatment for 2019-nCoV acute 78 respiratory disease

COVID-19: combining antiviral and anti-inflammatory 80 treatments

Dysregulated Type I Interferon and Inflammatory 82

Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice

Microbe

Exacerbated Innate Host Response to SARS-CoV in 85

Aged Non-Human Primates. Baric RS