Mast Cell and Eosinophil Activation Are Associated With COVID-19 and TLR-Mediated Viral Inflammation: Implications for an Anti-Siglec-8 Antibody.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection represents a global health crisis. Immune cell activation via pattern recognition receptors has been implicated as a driver of the hyperinflammatory response seen in COVID-19. However, our understanding of the specific immune responses to SARS-CoV-2 remains limited. Mast cells (MCs) and eosinophils are innate immune cells that play pathogenic roles in many inflammatory responses. Here we report MC-derived proteases and eosinophil-associated mediators are elevated in COVID-19 patient sera and lung tissues. Stimulation of viral-sensing toll-like receptors in vitro and administration of synthetic viral RNA in vivo induced features of hyperinflammation, including cytokine elevation, immune cell airway infiltration, and MC-protease production-effects suppressed by an anti-Siglec-8 monoclonal antibody which selectively inhibits MCs and depletes eosinophils. Similarly, anti-Siglec-8 treatment reduced disease severity and airway inflammation in a respiratory viral infection model. These results suggest that MC and eosinophil activation are associated with COVID-19 inflammation and anti-Siglec-8 antibodies are a potential therapeutic approach for attenuating excessive inflammation during viral infections.
Competing Interests: JS, SG, MB, TL, EB, AX, AW, JL,WK, and BY are employees of Allakos and/or own stock options in Allakos. BB and RS did not perform any of the experiments but are paid consultants on the scientific advisory board of Allakos, Inc., and own stock in Allakos. BB and RS are coinventors on existing Siglec-8–related patents and thus may be entitled to a share of royalties received by Johns Hopkins University from Allakos, Inc. on the potential sales of such products. BB and RS are also cofounders of Allakos, which makes him subject to certain restrictions under university policy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Gebremeskel, Schanin, Coyle, Butuci, Luu, Brock, Xu, Wong, Leung, Korver, Morin, Schleimer, Bochner and Youngblood.)