ABSTRACT
Interferons are key to the antiviral host defense, yet the therapeutic value of interferon for coronavirus disease 2019 (COVID-19) is unknown. Recombinant super-compound interferon (rSIFN-co) is a new genetically engineered interferon, thus we conducted a multicenter, randomized controlled trial (ChiCTR2000029638) to evaluate the efficacy and safety of recombinant super-compound interferon versus traditional interferon alpha added to baseline antiviral agents (lopinavir–ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19. Participants received rSIFN-co (12 million international units [IU], twice daily) or interferon alpha (5 million IU, twice daily) nebulization added to baseline antiviral agents for no more than 28 days. The primary outcome was the time to clinical improvement. Secondary outcomes included the overall rate of clinical improvement assessed on day 28，the time to radiological improvement and virus nucleic acid negative conversion, and adverse events. 94 patients hospitalized with moderate-to-severe COVID-19 were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon alpha group). Individuals in the rSIFN-co group showed shorter time to clinical improvement (11.5 days vs 14.0 days; P = 0.019) as compared to those in the interferon alpha group. The overall rate of clinical improvement on day 28 was much higher in the rSIFN-co group than that in the interferon alpha group (93.5% vs 77.1%; difference, 16.4%; 95% confidence interval 3% to 30%). The time to radiological improvement and the time to virus nucleic acid negative conversion were also much shorter in the rSIFN-co group (8.0 days vs 10.0 days, P = 0.002; 7.0 days vs 10.0 days, P = 0.018, respectively). Adverse events were reported in 13 (28.3%) patients in the rSIFN-co group and 18 (37.5%) patients in the interferon alpha group. No patients died during the study. Our study showed that rSIFN-co added to antiviral agents was safe and more efficient than interferon alpha plus antiviral agents in the treatment of moderate-to-severe COVID-19. Future clinical study of rSIFN-co therapy alone or combined with other antiviral therapy is warranted.