JAK-inhibition lisääminen COVID-19 terapioihin.

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 et al.  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; Baricitinib; Cytokine; JAK inhibitors; JAK-STAT pathway; Methotrexate PMID: 32392562 DOI:10.1159/000508247


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Pharmacol Res. 2020 May 6:104866. doi: 10.1016/j.phrs.2020.104866. [Epub ahead of print]

The CoV-2 outbreak: how hematologists could help to fight Covid-19.

Galimberti S¹, Baldini C² et al.

COVID-19 is a medical emergency, with 20 % of patients presenting with severe clinical manifestations. From the pathogenetic point of view, COVID-19 mimics two other well-known diseases characterized by cytokine storm and hyper-activation of the immune response, with consequent organ damage: acute graft-versus-host disease (aGVHD) and macrophage activation syndrome (MAS). Hematologists are confident with these situations requiring a prompt therapeutic approach for switching off the uncontrolled cytokine release; here, we discuss pros and cons of drugs that are already employed in hematology in the light of their possible application in COVID-19. The most promising drugs might be: Ruxolitinib, a JAK1/2 inhibitor, with a rapid and powerful anti-cytokine effect, tyrosine kinase inhibitors (TKIs), with their good anti-inflammatory properties, and perhaps the anti-Cd26 antibody Begelomab. We also present immunological data from gene expression experiments where TKIs resulted effective anti-inflammatory and pro-immune drugs. A possible combined treatment algorithm for COVID-19 is here proposed.
Copyright © 2020. Published by Elsevier Ltd.   KEYWORDS:

Baricitinib; Begelomab; COVID-19; GVHD; MAS; Ruxolitinib; TKIs; Tocilizumab PMID: 32387301 DOI: 10.1016/j.phrs.2020.104866