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Sci Rep
. 2021 Apr 13;11(1):8059.
doi: 10.1038/s41598-021-86859-y.
Role of interferon therapy in severe COVID-19: the COVIFERON randomized controlled trial
Ilad Alavi Darazam 1 2 3 , Shervin Shokouhi 1 2 3 , Mohamad Amin Pourhoseingholi 4 3 , Seyed Sina Naghibi Irvani 5 6 , Majid Mokhtari 7 3 , Minoosh Shabani 1 2 3 , Mahdi Amirdosara 8 3 , Parham Torabinavid 9 3 , Maryam Golmohammadi 1 3 , SayedPayam Hashemi 1 3 , Arsalan Azimi 10 3 , Mohammad Hossein Jafarazadeh Maivan 11 3 , Omidvar Rezaei 12 3 , Alireza Zali 13 3 , Mohammadreza Hajiesmaeili 8 3 , Hadiseh Shabanpour Dehbsneh 1 2 3 , Akram Hoseyni Kusha 1 2 3 , Maryam Taleb Shoushtari 1 2 3 , Negar Khalili 1 2 3 , Azam Soleymaninia 1 2 3 , Latif Gachkar 1 2 3 , Ali Khoshkar 14 3
Affiliations
- PMID: 33850184
- DOI: 10.1038/s41598-021-86859-y
Abstract
Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFN? compared to IFN? against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFN?1a and IFN?1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFN?1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFN?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?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?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?1a group and 30% in the IFN?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?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).