Caspases and therapeutic potential of caspase inhibitors in moderate-severe SARS-CoV-2 infection and long COVID.

Autor: Plassmeyer M; Amerimmune, Fairfax, VA, USA., Alpan O; Amerimmune, Fairfax, VA, USA., Corley MJ; Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, NY, USA., Premeaux TA; Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, NY, USA., Lillard K; Amerimmune, Fairfax, VA, USA., Coatney P; Amerimmune, Fairfax, VA, USA., Vaziri T; Amerimmune, Fairfax, VA, USA., Michalsky S; Amerimmune, Fairfax, VA, USA., Pang APS; Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, NY, USA., Bukhari Z; S.U.N.Y. Downstate Health Sciences University, Brooklyn, NY, USA., Yeung ST; Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, NY, USA., Evering TH; Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, NY, USA., Naughton G; Histogen, Inc, San Diego, CA, USA., Latterich M; Histogen, Inc, San Diego, CA, USA., Mudd P; Department of Emergency Medicine, Washington University School of Medicine, Saint Louis, MO, USA., Spada A; Histogen, Inc, San Diego, CA, USA., Rindone N; Histogen, Inc, San Diego, CA, USA., Loizou D; Histogen, Inc, San Diego, CA, USA., Ulrik Sønder S; Amerimmune, Fairfax, VA, USA., Ndhlovu LC; Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, NY, USA., Gupta R; S.U.N.Y. Downstate Health Sciences University, Brooklyn, NY, USA.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2022 Jan; Vol. 77 (1), pp. 118-129. Date of Electronic Publication: 2021 Jun 02.
DOI: 10.1111/all.14907
Abstrakt: Background: COVID-19 can present with lymphopenia and extraordinary complex multiorgan pathologies that can trigger long-term sequela.
Aims: Given that inflammasome products, like caspase-1, play a role in the pathophysiology of a number of co-morbid conditions, we investigated caspases across the spectrum of COVID-19 disease.
Materials & Methods: We assessed transcriptional states of multiple caspases and using flow cytometry, the expression of active caspase-1 in blood cells from COVID-19 patients in acute and convalescent stages of disease. Non-COVID-19 subject presenting with various comorbid conditions served as controls.
Results: Single-cell RNA-seq data of immune cells from COVID-19 patients showed a distinct caspase expression pattern in T cells, neutrophils, dendritic cells, and eosinophils compared with controls. Caspase-1 was upregulated in CD4+ T-cells from hospitalized COVID-19 patients compared with unexposed controls. Post-COVID-19 patients with lingering symptoms (long-haulers) also showed upregulated caspase-1activity in CD4+ T-cells that ex vivo was attenuated with a select pan-caspase inhibitor. We observed elevated caspase-3/7levels in red blood cells from COVID-19 patients compared with controls that was reduced following caspase inhibition.
Discussion: Our preliminary results suggest an exuberant caspase response in COVID-19 that may facilitate immune-related pathological processes leading to severe outcomes. Further clinical correlations of caspase expression in different stages of COVID-19 will be needed.
Conclusion: Pan-caspase inhibition could emerge as a therapeutic strategy to ameliorate or prevent severe COVID-19.
(© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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