COVID-19 Evidence Alerts
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Current best evidence for clinical care (more info)

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Treatment Alavi Darazam I, Shokouhi S, Pourhoseingholi MA, et al. Role of interferon therapy in severe COVID-19: the COVIFERON randomized controlled trial. Sci Rep. 2021 Apr 13;11(1):8059. doi: 10.1038/s41598-021-86859-y.

Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNß compared to IFNa against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNß1a and IFNß1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNß1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNß1b (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, IFNß1a 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 IFNß1b 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 IFNß1a group and 30% in the IFNß1b 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 IFNß1a arm. This finding needs further confirmation in larger studies.Trial Registration Number:, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768).

Discipline / Specialty Area Score
Intensivist/Critical Care
Infectious Disease
Hospital Doctor/Hospitalists
Internal Medicine
Comments from MORE raters

Intensivist/Critical Care rater

Very interesting approach, but as already stated within the article, there has to be a power analysis to work out the differences throughout the groups.

Internal Medicine rater

in this RCT out of Iran, 60 patients admitted with COVID-19, and either requiring oxygen OR with high resp rate (avg SaO2 in high 80s, so not particularly sick). All got HCQ one dose AND lopinivir/ritonavir FOLLOWED by IFN alpha (n=20), IFN Beta (n=20) or placebo. Given that BOTH HCQ and lopinivir/ritonavir are out of favor, this very small trial is already pretty muddy. No steroids were used. They saw benefit for alpha, not beta. Given the death rate in the placebo arm was 45% (really high for not sick people - the average for hospital patients is closer to 10-20%), I am not sure what to make of any of this. There is also very high rate of increased LFTs in all arms. Before I'd try this, I would like to see this compared to best usual care (dex+ Remdesivir + Toci+ IFN vs D-R-T + placebo), and would like to know that the liver is not adversely affected with the Rem+ IFN combo.

Respirology/Pulmonology rater

This is a very small unblinded study where three groups of 20 patients with severe Covid-19 were given one of two interferons or a placebo along with hydroxychloroquine and lopinavir/ritonavir. I do not think it is possible to draw any firm conclusion from this small study about whether the treatments actually worked.