Role of interferon therapy in severe COVID-19: the COVIFERON randomized controlled trial

Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFN beta compared to IFN alpha against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFN beta 1a and IFN beta 1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFN beta 1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFN beta 1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400 mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFN beta 1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI 1.10-5.17, P-value=0.031) while the IFN beta 1b indicated no significant difference compared with the control; HR; 1.42, (95% CI 0.63-3.16, P-value=0.395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFN beta 1a group and 30% in the IFN beta 1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFN beta 1a arm. This finding needs further confirmation in larger studies.Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768).

Automated summary

The study investigated the effects of IFN beta 1a and IFN beta 1b on combating Coronaviruses, with IFN beta 1a showing a significant difference in Time To Clinical Improvement compared to the control group, while IFN beta 1b did not. The findings indicated a slightly lower overall mortality rate in the IFN beta 1a group compared to the other two groups.