Int Arch Allergy Immunol. JAK Inhibition as a New Treatment Strategy for Patients with COVID-19

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Int Arch Allergy Immunol. 2020 May 11:1-9. doi: 10.1159/000508247. [Epub ahead of print]
JAK Inhibition as a New Treatment Strategy for Patients with COVID-19.


Seif F^1,2, Aazami H³, Khoshmirsafa M⁴, Kamali M⁵, Mohsenzadegan M⁶, Pornour M⁷, Mansouri D^8,9,10.

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Abstract

After the advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the outbreak of coronavirus disease 2019 (COVID-19) commenced across the world. Understanding the Immunopathogenesis of COVID-19 is essential for interrupting viral infectivity and preventing aberrant immune responses before a vaccine can be developed. In this review, we provide the latest insights into the roles of angiotensin-converting enzyme II (ACE2) and Ang II receptor-1 (AT1-R) in this disease. Novel therapeutic strategies, including recombinant ACE2, ACE inhibitors, AT1-R blockers, and Ang 1-7 peptides, may prevent or reduce viruses-induced pulmonary, cardiac, and renal injuries. However, more studies are needed to clarify the efficacy of these therapeutics. Furthermore, considering the common role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in AT1-R expressed on peripheral tissues and cytokine receptors on the surface of immune cells, potential targeting of this pathway using JAK inhibitors (JAKinibs) is suggested as a promising approach in patients with COVID-19 who are admitted to hospitals. In addition to antiviral therapy, potential ACE2- and AT1-R-inhibiting strategies, and other supportive care, we suggest other potential JAKinibs and novel anti-inflammatory combination therapies that affect the JAK-STAT pathway in patients with COVID-19. Since the combination of MTX and baricitinib leads to outstanding clinical outcomes, the addition of baricitinib to MTX might be a potential strategy.
? 2020 S. Karger AG, Basel.



KEYWORDS:

Angiotensin receptor blocker; Angiotensin-converting enzyme inhibitor; Bricitinib; Cytokine; JAK inhibitors; JAK-STAT pathway; Methotrexate


PMID:32392562DOI:10.1159/000508247