A phase I trial of cyclosporine for hospitalized patients with COVID-19
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Abstract
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 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.
RESULTS
Five 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.
CONCLUSION
Short 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 REGISTRATION
This trial was registered on ClinicalTrials.gov (Investigational New Drug Application no. 149997; ClinicalTrials.gov NCT04412785).
FUNDING
This study was internally funded by the Center for Cellular Immunotherapies.
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SciScore for 10.1101/2021.06.10.21258714: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This investigator-initiated trial protocol was approved by the Institutional Review Board (IRB) at the University of Pennsylvania and was overseen by the Center for Cellular Immunotherapies (IND#149997, ClinicalTrials.gov identifier: NCT04412785).
Consent: Informed consent was obtained from each patient.Sex as a biological variable Also excluded were pregnant or lactating women and patients receiving investigational vaccines for SARS-CoV-2. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Statistical analyses were performed using Prism 8 GraphPad (GraphPad Software). Prismsuggested: (PRISM, RRID:SCR_005375)SciScore for 10.1101/2021.06.10.21258714: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This investigator-initiated trial protocol was approved by the Institutional Review Board (IRB) at the University of Pennsylvania and was overseen by the Center for Cellular Immunotherapies (IND#149997, ClinicalTrials.gov identifier: NCT04412785).
Consent: Informed consent was obtained from each patient.Sex as a biological variable Also excluded were pregnant or lactating women and patients receiving investigational vaccines for SARS-CoV-2. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Statistical analyses were performed using Prism 8 GraphPad (GraphPad Software). Prismsuggested: (PRISM, RRID:SCR_005375)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:There are several limitations to this study. Given the variable epidemiology of COVID-19 and the changing therapeutics during our study period, our enrollment was impacted and the number studied is small. The small numbers also affected our ability to estimate whether there was a significant clinical effect for our patients, independently of those related to corticosteroids and remdesivir. In summary, we show that CSA is a safe and potentially effective therapeutic intervention for patients with SARS-CoV-2 infection. Its anti-inflammatory properties, wide availability, safety and low cost make it a particularly attractive modality for use in resource-limited settings. A prospective randomized controlled trial testing the efficacy of cyclosporine for the treatment of COVID-19 pneumonia is registered in Spain [20]. Based on our results further large-scale trials are warranted to explore the safety and benefits of this intervention globally.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04412785 Active, not recruiting Cyclosporine in Patients With Moderate COVID-19 Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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