Combined Therapy of Ciclosporin Plus Favipiravir in the Management of Patients with Severe COVID-19, not Responding to Dexamethasone: A non-Controlled Prospective Trial

Abstract

Background: Regarding the COVID-19 pandemic, potential therapeutic agents are being evaluated almost every day. Ciclosporin, a calcineurin inhibitor, is characterized by beneficial antiviral and immunomodulatory effects. The present study aimed to evaluate the efficacy of ciclosporin in managing COVID-19.

Methods: This study was a prospective non-controlled clinical trial carried out on 20 patients. Confirmed COVID-19 patients received two doses of ciclosporin (10 mg/kg and 5 mg/kg injections) 24 h apart. Mortality rate and the lengths of intensive care unit (ICU) and hospital stays were assessed for all 20 patients.

Results: The mortality rate and the need for mechanical ventilation were calculated as 50%. The percentage of ICU admission was 70%. The lengths of ICU and hospital stays were 8.13 ± 6.81 and 14.25 ± 8.55 days, respectively. The levels of ferritin and white blood cells were significantly higher after injecting the second dose of ciclosporin. Seven patients (35%) had radiologically improved lungs after ciclosporin therapy.

Conclusion: It seems that the protocol of two doses of ciclosporin in combination with favipiravir does not have favorable effects among COVID-19 patients that do not respond to dexamethasone. Controlled trials are needed to confirm the results.

Keywords: COVID-19; Calcineurin inhibitors; Ciclosporin; SARS-CoV-2.

Fig. 1

The CONSORT diagram of the study.

Fig. 2

Chest CT images of seven patients (P1- P7) who had radiologically improved lung after receiving cyclosporine at the time of admission. Non-contrast enhanced CT images of patient 1 (P1- A) showed bilateral patchy consolidations in both peri-bronchovascular and subpleural distribution (*) that improved considerably (arrow) after receiving cyclosporine (P1- B). Patient 2 had segmental peri-bronchovascular and subpleural consolidations (*), more confluent than patient 1 (P2- C) which improved significantly (arrow) after medical therapy (P2-D). Patient 3 had bibasilar infiltrations as well as subsegmental patchy consolidation with irregular border within right middle lobe (*) (P3-E). Repeated CT images (P3-F) after cyclosporine administration show substantial decrease lung infiltrations (arrow). Patients 4, 5, 6 and 7 CT images also showed similar Covid-19 imaging manifestations with considerable decreased in the severity of lung infiltration before (*) and after (arrow) cyclosporine therapy (P4, P5, P6 and p7).