Frontline doc unpacks results of a new clinical trial that shows interferon may reduce the odds of severe illness or death from Covid-19
The COVID-19 Treatment Guidelines Panel recommends against the use of interferons for the treatment of patients with severe or critical COVID-19, except in a clinical trial (AIII). There are insufficient data to recommend either for or against the use of interferon beta for the treatment of early (i.e., <7 days from symptom onset) mild and moderate COVID-19.
Studies have shown no benefit of interferons in patients with other coronavirus infections (i.e., Middle East respiratory syndrome [MERS], severe acute respiratory syndrome [SARS]) who have severe or critical disease. In addition, interferons have significant toxicities that outweigh the potential for benefit. Interferons may have antiviral activity early in the course of infection. However, there is insufficient data to assess the potential benefit of interferon use during early disease versus the toxicity risks.
Clinical Data for COVID-19
Press release, July 20, 2020: A double-blind, placebo-controlled trial conducted in the United Kingdom evaluated inhaled interferon beta-1a (once daily for up to 14 days) in nonventilated patients hospitalized with COVID-19. Compared to the patients receiving placebo (n = 50), the patients receiving inhaled interferon beta-1a (n = 48) were more likely to recover to ambulation without restrictions (HR 2.19; 95% CI, 1.03–4.69; P = 0.04), had decreased odds of developing severe disease (OR 0.21; 95% CI, 0.04–0.97; P = 0.046), and had less breathlessness. Additional detail is required to fully evaluate these findings and their implications. Of note, inhaled interferon beta-1a as used in this study is not commercially available in the United States.1
Preprint manuscript posted online, July 13, 2020: An open-label, randomized trial at a single center in Iran evaluated subcutaneous interferon beta-1a (three times weekly for 2 weeks) in patients with severe COVID-19. There was no difference in the primary outcome of time to clinical response between the interferon beta-1a group (n = 42) and the control group (n = 39), and there was no difference between the groups in overall length of hospital stay, length of intensive care unit stay, or duration of mechanical ventilation. The reported 28-day overall mortality was lower in the interferon beta-1a group; however, four patients in the interferon beta-1a group who died before receiving the fourth dose of interferon beta-1a were excluded from the analysis, which makes it difficult to interpret these results.2
Combination of Interferon Beta-1b, Lopinavir/Ritonavir, and Ribavirin in the Treatment of Hospitalized Patients With COVID-19
An open-label, Phase 2 clinical trial randomized 127 participants (median age of 52 years) 2:1 to combination antiviral therapy or lopinavir/ritonavir. In the combination antiviral therapy group, the treatment regimen differed by time from symptom onset to hospital admission. Participants hospitalized within 7 days of symptom onset (n = 76) were randomized to triple drug therapy (interferon beta-1b 8 million units administered subcutaneously every other day for up to 7 days total, lopinavir/ritonavir, and ribavirin); those hospitalized ≥7 days after symptom onset (n = 51) were randomized to double therapy (lopinavir/ritonavir and ribavirin) because of concerns regarding potential inflammatory effects of interferon. Patients in the control group received lopinavir/ritonavir alone regardless of the time from symptom onset to hospitalization. The study participants were patients in Hong Kong with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were hospitalized, regardless of disease severity, until they had two negative nasopharyngeal (NP) swab tests.
The time to a negative result on a polymerase chain reaction SARS-CoV-2 test on an NP swab (the primary endpoint) was shorter in the combination therapy group than in the control group (median of 7 days vs. 12 days; P = 0.001). The combination group had more rapid clinical improvement as assessed by the National Early Warning Score (NEWS) 2 and Sequential Organ Failure Assessment (SOFA) score and a shorter hospital stay (median of 9 days for the combination group vs. 14.5 days for the control group; P = 0.016). There was no difference in oxygen use between the groups. The antiviral and clinical effect was more pronounced in the patients hospitalized within 7 days of symptom onset, suggesting that interferon beta-1b with or without ribavirin was the critical component of the combination antiviral therapy. The study provides no information about the effect of interferon beta-1b when administered ≥7 days after symptom onset.3