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Caspases and therapeutic potential of caspase inhibitors in moderate-severe SARS-CoV-2 infection and long COVID.
Plassmeyer, Matthew; Alpan, Oral; Corley, Michael J; Premeaux, Thomas A; Lillard, Kimberleigh; Coatney, Paige; Vaziri, Tina; Michalsky, Suzan; Pang, Alina P S; Bukhari, Zaheer; Yeung, Stephen T; Evering, Teresa H; Naughton, Gail; Latterich, Martin; Mudd, Philip; Spada, Alfred; Rindone, Nicole; Loizou, Denise; Ulrik Sønder, Søren; Ndhlovu, Lishomwa C; Gupta, Raavi.
  • 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.
Allergy ; 77(1): 118-129, 2022 01.
Article in English | MEDLINE | ID: covidwho-1597019
ABSTRACT

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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Caspase Inhibitors / COVID-19 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Long Covid Limits: Humans Language: English Journal: Allergy Year: 2022 Document Type: Article Affiliation country: All.14907

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Caspase Inhibitors / COVID-19 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Long Covid Limits: Humans Language: English Journal: Allergy Year: 2022 Document Type: Article Affiliation country: All.14907