Effectiveness and safety of cyclosporine A in moderate to severe COVID-19: a randomized, open-label trial

Abstract

Abstract COVID-19 severity is strongly associated with hyperinflammation. Cyclosporine A (CSA), an interleukin-2 inhibitor with immunomodulatory and antiviral activity, has been proposed as a potential adjunctive therapy. This study evaluated the safety and efficacy of CSA in patients with moderate to severe COVID-19. We conducted A randomized, open-label phase III trial was conducted involving 66 patients with COVID-19. Participants were assigned to one of two groups: the CSA group (n = 23), receiving 6 mg/kg/day for 7–14 days, and a standard treatment group (n = 43). Clinical improvement (WHO ordinal scale) was the main goal, with C-reactive protein (CRP), ferritin, interleukin-6 ( IL-6), and D-dimer, and safety monitoring for 28 days as secondary outcomes significant differences in enrolment. The time to clinical improvement was significantly shorter in the CSA group (4.3 ± 1.0 vs. 5.1 ± 2.3 days; p  = 0.025). Oxygen supplementation was used in 7 patients (30.43%) versus 12 patients (27.91%) in the standard group, with a p -value of 0.828. No significant differences occurred in the WHO ordinal scale, advanced respiratory support, or mortality. No secondary infections occurred. CSA improved oxygen saturation and reduced CRP and IL-6; differences in saturation at day 14 were not significant. D-dimer and ferritin levels were lower at day 14, with no differences observed at day 7. Cyclosporine did not significantly improve ordinal scale outcomes. However, it was associated with a shorter time to clinical improvement and favorable modulation of inflammatory markers in patients with COVID-19 and cytokine storm, without major safety concerns.