Efficacy and safety of cyclosporine in the management of coronavirus disease 2019: A protocol for systematic review and meta-analysis

Abstract

Introduction Cyclosporine may improve the clinical course and outcomes of Coronavirus disease 2019 (COVID-19) due to its antiviral and anti-cytokine effects as shown in vitro. A few ongoing trials are exploring the benefit of adding it to the standard of care (SOC) of COVID-19 patients. Objectives The primary objective is to evaluate the severity of COVID-19, determined by oxygen saturation, intensive care unit (ICU) admission, or the World Health Organization COVID-19 clinical severity scale in patients treated with oral or intravenous cyclosporine added to SOC compared SOC alone or placebo. Secondary objectives include mortality, length of hospitalization, length of ICU stay, and laboratory measurements as well as the safety outcomes of cyclosporine. Methodology A systematic review and meta-analysis of randomized clinical trials and observational studies that compared cyclosporine to placebo or SOC in COVID-19 patients will be conducted. PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Google Scholar, and ClinicalTrials.gov will be explored for studies that satisfy pre-specified inclusion criteria. Quality assessment of all included studies will be performed. Meta-analyses will be done utilizing random effect models to estimate the effect of cyclosporine on the severity of COVID-19. Heterogeneity will be assessed utilizing Q statistics. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. Results The result of this synthesis will inform potential changes in the management of COVID-19 patients, especially regarding the role of calcineurin inhibitors. Additionally, it will serve as hypothesis generating for potential future prospective studies.