tetano
Editor, Senior Moderator
JCI Insight
. 2022 May 10;e155682.
doi: 10.1172/jci.insight.155682. Online ahead of print.
Phase 1 trial of cyclosporine for hospitalized patients with COVID-19
Emily A Blumberg[SUP] 1 [/SUP], Julia Han Noll[SUP] 2 [/SUP], Pablo Tebas[SUP] 1 [/SUP], Joseph A Fraietta[SUP] 2 [/SUP], Ian Frank[SUP] 1 [/SUP], Amy E Marshall[SUP] 2 [/SUP], Anne Chew[SUP] 2 [/SUP], Elizabeth A Veloso[SUP] 2 [/SUP], Alison Carulli[SUP] 3 [/SUP], Walter Rogal[SUP] 2 [/SUP], Avery L Gaymon[SUP] 2 [/SUP], Aliza H Schmidt[SUP] 2 [/SUP], Tiffany Barnette[SUP] 2 [/SUP], Renee Jurek[SUP] 2 [/SUP], Rene Martins[SUP] 4 [/SUP], Briana M Hudson[SUP] 5 [/SUP], Kalyan Chavda[SUP] 5 [/SUP], Christina M Bailey[SUP] 5 [/SUP], Sarah E Church[SUP] 5 [/SUP], Hooman Noorchashm[SUP] 6 [/SUP], Wei-Ting Hwang[SUP] 7 [/SUP], Carl H June[SUP] 8 [/SUP], Elizabeth O Hexner[SUP] 1 [/SUP]
Affiliations
Abstract
Background: Coronavirus Disease 2019 (COVID-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.
Methods: To test whether a short course of CSA was safe in COVID-19 patients, we treated 10 hospitalized, oxygen requiring, non-critically ill patients with CSA (starting dose of 9mg/kg/day). We evaluated patients for clinical response and adverse events and measured serum cytokines and chemokines associated with COVID-19 hyper-inflammation and conducted gene-expression analyses.
Results: Five subjects experienced adverse events, none were serious; transaminitis was most common. No subject required intensive care unit (ICU)-level care and all patients were discharged alive. CSA treatment was associated with significant reductions in serum cytokines and chemokines important in COVID-19 hyper-inflammation, including CXCL10. Following CSA administration, we also observed a significant reduction in type I interferon gene expression signatures and other transcriptional profiles associated with exacerbated hyper-inflammation in the peripheral blood cells of these patients.
Conclusions: Short courses of CSA appear safe and feasible in COVID-19 patients requiring oxygen and may be a useful adjunct in resource-limited health care settings.
Trial registration: This trial was registered on ClinicalTrials.gov (IND#149997, ClinicalTrials.gov identifier: NCT04412785).
Funding: This study was internally funded by the Center for Cellular Immunotherapies.
Keywords: COVID-19; Chemokines; Cytokines.
. 2022 May 10;e155682.
doi: 10.1172/jci.insight.155682. Online ahead of print.
Phase 1 trial of cyclosporine for hospitalized patients with COVID-19
Emily A Blumberg[SUP] 1 [/SUP], Julia Han Noll[SUP] 2 [/SUP], Pablo Tebas[SUP] 1 [/SUP], Joseph A Fraietta[SUP] 2 [/SUP], Ian Frank[SUP] 1 [/SUP], Amy E Marshall[SUP] 2 [/SUP], Anne Chew[SUP] 2 [/SUP], Elizabeth A Veloso[SUP] 2 [/SUP], Alison Carulli[SUP] 3 [/SUP], Walter Rogal[SUP] 2 [/SUP], Avery L Gaymon[SUP] 2 [/SUP], Aliza H Schmidt[SUP] 2 [/SUP], Tiffany Barnette[SUP] 2 [/SUP], Renee Jurek[SUP] 2 [/SUP], Rene Martins[SUP] 4 [/SUP], Briana M Hudson[SUP] 5 [/SUP], Kalyan Chavda[SUP] 5 [/SUP], Christina M Bailey[SUP] 5 [/SUP], Sarah E Church[SUP] 5 [/SUP], Hooman Noorchashm[SUP] 6 [/SUP], Wei-Ting Hwang[SUP] 7 [/SUP], Carl H June[SUP] 8 [/SUP], Elizabeth O Hexner[SUP] 1 [/SUP]
Affiliations
- PMID: 35536669
- DOI: 10.1172/jci.insight.155682
Abstract
Background: Coronavirus Disease 2019 (COVID-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.
Methods: To test whether a short course of CSA was safe in COVID-19 patients, we treated 10 hospitalized, oxygen requiring, non-critically ill patients with CSA (starting dose of 9mg/kg/day). We evaluated patients for clinical response and adverse events and measured serum cytokines and chemokines associated with COVID-19 hyper-inflammation and conducted gene-expression analyses.
Results: Five subjects experienced adverse events, none were serious; transaminitis was most common. No subject required intensive care unit (ICU)-level care and all patients were discharged alive. CSA treatment was associated with significant reductions in serum cytokines and chemokines important in COVID-19 hyper-inflammation, including CXCL10. Following CSA administration, we also observed a significant reduction in type I interferon gene expression signatures and other transcriptional profiles associated with exacerbated hyper-inflammation in the peripheral blood cells of these patients.
Conclusions: Short courses of CSA appear safe and feasible in COVID-19 patients requiring oxygen and may be a useful adjunct in resource-limited health care settings.
Trial registration: This trial was registered on ClinicalTrials.gov (IND#149997, ClinicalTrials.gov identifier: NCT04412785).
Funding: This study was internally funded by the Center for Cellular Immunotherapies.
Keywords: COVID-19; Chemokines; Cytokines.