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