| Autor: |
Oral Alpan, Philip A. Mudd, Suzan Michalsky, Thomas A. Premeaux, Teresa H. Evering, Gail Naughton, Lishomwa C. Ndhlovu, Martin Latterich, Zaheer Bukhari, Tina Vaziri, Nicole Rindone, Alina P.S. Pang, Denise Loizou, Matthew Plassmeyer, Stephen T. Yueng, Kimberleigh Lillard, Alfred Spada, Michael J. Corley, Paige Coatney, Raavi Gupta |
| Rok vydání: |
2020 |
| Předmět: |
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| DOI: |
10.1101/2020.11.02.20223636 |
| Popis: |
Currently, there is no effective vaccine and only one FDA approved early-stage therapy against SARS-CoV-2 infection as an indication to prevent disease progression. Cellular caspases play a role in the pathophysiology of a number of disorders that the co-morbid conditions seen in severe COVID-19 disease. In this study, we assessed transcriptional states of caspases in blood cells from COVID-19 patients. Gene expression levels of select caspases were increased inin vitroSARS-CoV-2 infection models and single cell RNA-Seq data of blood from COVID-19 patients showed a distinct caspase expression in T cells, neutrophils, and dendritic cells. Flow cytometric evaluation of CD4 T cells showed up-regulation of caspase-1 in hospitalized COVID-19 patients compared to unexposed controls. Convalescent COVID-19 patients with lingering symptoms (“long haulers”) showed persistent up-regulation of caspase-1 in CD4 T cells that was attenuatedex vivofollowing co-culture with a select pan-caspase inhibitor. Further, we observed elevated caspase-3 levels in red blood cells from COVID-19 patients compared to controls that were responsive to caspase inhibition. Our results expose an exuberant caspase response in COVID-19 that may facilitate immune-related pathological processes leading to severe outcomes. Pan-caspase inhibition could emerge as a therapeutic strategy to ameliorate or prevent severe COVID-19 outcomes. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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