Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial

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.

Beyond Vaccines: Clinical Status of Prospective COVID-19 Therapeutics

“…This treatment regimen significantly improved clinical outcomes, including cough-relief, CTimaging, and vRNA negativity, altogether favoring an early discharge from hospitalization (144). Another Phase-II clinical trial (ChiCTR2000029638) was conducted on moderate to severe COVID-19 patients to evaluate the safety and efficacy of Recombinant Super-Compound Interferon (rSIFN-co) versus traditional nebulized IFNa-2b, alongside standard antivirals (LPV/r or Umifenovir) (145). The trial observed that cotreatment with rSIFN-co was safer and more efficacious than traditional IFNa-2b for treating moderate to severe COVID-19, warranting further clinical trials of rSIFN, alone or in combination with other antiviral agents.…”

Clinical Efficacy and Safety of Antiviral Drugs in the Extended Use against COVID-19: What We Know So Far

“…The authors concluded that the rhIFN-α strictly protected medical staff with the augmented safeguards. A randomized multicenter clinical trial was conducted by Li et al [92] to evaluate the efficacy of recombinant super compound-interferon (rSIFN-co) with traditional IFN in COVID-19 treatment, and the rSINF group showed better clinical improvement time (rSIFN = 11.5 days, IFN-alpha = 14 days), clinical improvement rate (rSIFN = 93.5%, IFN-alpha = 77.1%), radiological improvement time (rSIFN = 8 days, IFN-alpha = 10 days), and viral shedding time (rSIFN = 7 days, IFN-alpha = 10 days). Another randomized control trial was reported wherein IFN-alpha 2b exerted greater efficacy in the duration of hospitalization and viral clearance [53].…”

Prevalence of comorbid tuberculosis amongst COVID‐19 patients: A rapid review and meta‐analysis

“…A total of 114 eligible studies 2 , 3 , 4 , 5 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ,…”