Abstract
Background
There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir–ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19.
Method
In this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion.
Results
A total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81, p = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days ( p = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days ( p = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups.
Conclusions and relevance
rSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.
Key messages
There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus. In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir–ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.
【저자키워드】 COVID-19, SARS CoV-2, interferon-alpha, recombinant super-compound interferon, 【초록키워드】 Treatment, coronavirus disease, antiviral therapy, interferon-alpha, Coronavirus disease 2019, coronavirus, clinical trial, pandemic, Trial, Lopinavir, Ritonavir, interferon, severe acute respiratory syndrome Coronavirus, adverse events, Randomized, nucleic acid, outbreak, immune responses, Antiviral agents, Patient, Effectiveness, death, Clinical improvement, Middle East respiratory syndrome Coronavirus, Alpha, multicenter, Interferon alpha, respiratory, umifenovir, antiviral agent, Clinical efficacy, primary endpoint, adaptive immune responses, Middle East, Lopinavir–ritonavir, rSIFN-co, ARMS, acute respiratory syndrome, Adverse, Endpoint, 95% CI, acute respiratory syndrome coronavirus, Secondary endpoints, Negative conversion, baseline antiviral agents, head, interferon-alpha group, interferon-alpha nebulization, moderate-to-severe COVID-19, radiological improvement, rSIFN-co group, rSIFN-co therapy, traditional interferon-alpha, virus nucleic acid, participant, effective therapy, respiratory syndrome coronavirus, secondary, event, Result, shown, added, assigned, groups, 1:1, baseline antiviral agent, lopinavir–ritonavir or umifenovir, patients hospitalized, rSIFN-co nebulization, 【제목키워드】 Treatment, interferon-alpha, randomised, Effect,