A phase I trial of cyclosporine for hospitalized patients with COVID-19.

Autor:	Blumberg EA; Department of Medicine, Division of Infectious Diseases., Noll JH; Center for Cellular Immunotherapies, and.; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Pennsylvania, USA., Tebas P; Department of Medicine, Division of Infectious Diseases., Fraietta JA; Center for Cellular Immunotherapies, and.; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Pennsylvania, USA., Frank I; Department of Medicine, Division of Infectious Diseases., Marshall A; Center for Cellular Immunotherapies, and., Chew A; Center for Cellular Immunotherapies, and., Veloso EA; Center for Cellular Immunotherapies, and., Carulli A; Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA., Rogal W; Center for Cellular Immunotherapies, and., Gaymon AL; Center for Cellular Immunotherapies, and., Schmidt AH; Center for Cellular Immunotherapies, and., Barnette T; Center for Cellular Immunotherapies, and., Jurek R; Center for Cellular Immunotherapies, and., Martins R; Center for Cellular Immunotherapies, and., Hudson BM; NanoString Technologies Inc., Seattle, Washington, USA., Chavda K; NanoString Technologies Inc., Seattle, Washington, USA., Bailey CM; NanoString Technologies Inc., Seattle, Washington, USA., Church SE; NanoString Technologies Inc., Seattle, Washington, USA., Noorchashm H; Yardley, Pennsylvania, USA., Hwang WT; Department of Biostatistics, Epidemiology and Informatics and., June CH; Center for Cellular Immunotherapies, and.; Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Pennsylvania, USA.; Department of Medicine, Division of Hematology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania USA., Hexner EO; Department of Medicine, Division of Hematology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2022 Jun 08; Vol. 7 (11). Date of Electronic Publication: 2022 Jun 08.
DOI:	10.1172/jci.insight.155682
Abstrakt:	BACKGROUNDCOVID-19 remains a global health emergency with limited treatment options, lagging vaccine rates, and inadequate healthcare resources in the face of an ongoing calamity. The disease is characterized by immune dysregulation and cytokine storm. Cyclosporine A (CSA) is a calcineurin inhibitor that modulates cytokine production and may have direct antiviral properties against coronaviruses.METHODSTo test whether a short course of CSA was safe in patients with COVID-19, we treated 10 hospitalized, oxygen-requiring, noncritically ill patients with CSA (starting at a dose of 9 mg/kg/d). We evaluated patients for clinical response and adverse events, measured serum cytokines and chemokines associated with COVID-19 hyperinflammation, and conducted gene-expression analyses.RESULTSFive participants experienced adverse events, none of which were serious; transaminitis was most common. No participant required intensive care unit-level care, and all patients were discharged alive. CSA treatment was associated with significant reductions in serum cytokines and chemokines important in COVID-19 hyperinflammation, including CXCL10. Following CSA administration, we also observed a significant reduction in type I IFN gene expression signatures and other transcriptional profiles associated with exacerbated hyperinflammation in the peripheral blood cells of these patients.CONCLUSIONShort courses of CSA appear safe and feasible in patients with COVID-19 who require oxygen and may be a useful adjunct in resource-limited health care settings.TRIAL REGISTRATIONThis trial was registered on ClinicalTrials.gov (Investigational New Drug Application no. 149997; ClinicalTrials.gov NCT04412785).FUNDINGThis study was internally funded by the Center for Cellular Immunotherapies.
Databáze:	MEDLINE
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