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Review
. 2020 Dec;9(1):1514-1522.
doi: 10.1080/22221751.2020.1785336.

Kawasaki-like diseases and thrombotic coagulopathy in COVID-19: delayed over-activation of the STING pathway?

Jean-Marie Berthelot  1 , Ludovic Drouet  2   3 , Frédéric Lioté  4   5   6
Affiliations
Review

Kawasaki-like diseases and thrombotic coagulopathy in COVID-19: delayed over-activation of the STING pathway?

Jean-Marie Berthelot et al. Emerg Microbes Infect. 2020 Dec.

Abstract

We previously made the hypothesis that STING contributes to COVID-19. The present review detail new arguments for over-activation of STING pathways in COVID-19, following the description of hyper-coagulability and Kawasaki-like diseases in children. Indeed, Kawasaki disease is induced by overreaction of innate cells following exposition to various viruses, including herpes viruses which trigger STING. It predisposes to diffuse vasculitis and aneurysms, whereas STING is over-expressed in arterial aneurisms. The redness at the inoculation site of bacillus Calmette-Guérin, a specific feature of Kawasaki disease, is reproduced by activation of the STING pathway, which is inhibited upstream by aspirin, intravenous immunoglobulins, and Vitamin-D. SARS-CoV2 binding to ACE2 can lead to excessive angiotensin II signaling, which activates the STING pathway in mice. Over-activation of the STING-pathway promotes hyper-coagulability through release of interferon-β and tissue factor by monocytes-macrophages. Aspirin and dipyridamole, besides their anti-platelet activity, also reduce tissue factor procoagulant activity, and aspirin inhibits the STING pathway upstream of STING. Aspirin and dipyridamole may be used, in combination with drugs blocking downstream the activation of the STING pathway, like inhibitors of IL-6R and JAK/STAT pathways. The risk of bleeding should be low as bleeding has not been reported in severe COVID-19 patients.

Keywords: ACE2; COVID-19; Kawasaki disease; STING; aspirin; coagulopathy; thrombosis; tissue factor.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

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