An investigation into the beneficial effects of high-dose interferon beta 1-a, compared to low-dose interferon beta 1-a in severe COVID-19: The COVIFERON II randomized controlled trial

Abstract

Introduction Coronavirus disease 2019 (COVID-19) has been a serious obstacle in front of public health. Interferon-beta 1a (IFN-β 1a) has been used to treat patients with COVID-19. We aimed to compare the effectiveness of high-dose IFN-β 1a compared to low dose IFN-β 1a in severe COVID-19 cases. Methods In this randomized, controlled, and clinical trial, eligible patients with confirmed SARS-CoV-2 infections were randomly assigned to receive one of the two following therapeutic regimens: The intervention group was treated with high-dose IFN-β 1a (Recigen) (Subcutaneous injections of 88μg (24 million IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400mg/100 mg twice a day for 10 days, orally) and the control group was treated with low-dose IFN-β 1a (Recigen) (Subcutaneous injections of 44μg (12 million IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400mg/100 mg twice a day for 10 days, orally). Result A total of 168 COVID- 19 confirmed patients underwent randomization; 83 were assigned to the intervention group and 85 were assigned to the control group. Median Time To Clinical Improvement (TTIC) for cases treated with low-dose IFN-β1a was shorter than that for cases treated with high-dose IFN-β1a (6 vs 10 days; P=0.018). The mortality rates in intervention and control group were 41% and 36.5%, respectively. Conclusion The use of high-dose IFN-β 1a did not improve TTCI in hospitalized patients with moderate to severe COVID-19. Also, it did not have any significant effect on mortality reduction compared with treating with low-dose IFN-β 1a. Trial registration: This trial has been registered as ClinicalTrials.gov, NCT04521400.

Efficacy of Interferon-β in Moderate-to-Severe Hospitalised Cases of COVID-19: A Systematic Review and Meta-analysis

“…Of these 24 studies, 16 were excluded as they were either nonclinical or non-randomised studies. The remaining eight studies [ 10 , 16 – 22 ] were included in qualitative synthesis (systematic review), but one study [ 22 ] was excluded from meta-analysis as it used IFN in experimental as well as in the control arm. All seven of the remaining articles were included in the meta-analysis (Fig.…”

“…IFN-β, a subtype of type I IFN, has been investigated widely as one of the treatment options for COVID-19 as a repurposed drug [ 11 , 16 – 22 ]. The present piece of work is a systematic review and meta-analysis of the randomised controlled trials evaluating the efficacy of IFN-β in terms of mortality, LOHS and time to clinical improvement.…”

“…IFN-β1b: SC, 8 MIU on Days 1, 3, 6 WHO solidarity trial. 2020 (NCT04315948) [ 21 ] Open-label RCT Hospitalised adults with COVID-19 IFN-β1a + LPV/r + SOC SOC + LPV/r 1 o Mortality 2 o Initiation of mechanical ventilation, duration of hospitalisation SC, 44 mcg, on Days 1, 3 & 6 IV, 10 mcg daily for 6 days Darazam et al 2021 (NCT04521400) [ 22 ] RCT Hospitalised adults with COVID-19 IFN-β1a (high dose) + LPV/r + SOC IFN-β1a (low dose) + LPV/r + SOC 1 o Time to clinical improvement 2 o Mortality SC, 88 mcg (24 MIU) on days 1, 3, 6 SC, 44 mcg (12 MIU) on Days 1, 3, 6 1 o Primary outcome, 2 o Secondary outcome ATV/r atazanavir and ritonavir combination, COVID-19 Coronavirus disease 2019, HCQ hydroxychloroquine, IFN interferon, IU International Unit, IV intravenous, LPV/r lopinavir and ritonavir combination, mcg microgram, MIU million/mega International Unit, RCT randomized controlled trial, SC subcutaneous, SOC standard of care a LPV/r[ 10 ] b Local standard of care[ 16 ] c + LPV/r or ATV/r + HCQ for 7–10 days [ 18 , 19 ] d LPV/r + HCQ single dose[ 20 ] …”

“…A total of eight randomised control trials were included in the systematic review, of which seven were included in the meta-analysis. One study [ 22 ] was excluded from the meta-analysis as IFN-β (although in different doses) was used in both of the study arms (Table 1 ).…”

Combinations of drugs might increase the survival chances of COVID-19 patients: Literature review till date

“…Peiffer et.al conducted a small trial and reported that COVID-19 patients who received Nebulised (interferon) IFN-β 1a had significantly greater odds of clinical improvement [1116]. Higher or lower doses of IFN-β 1a in moderate to severe COVID-19 patients didn't show any improvement in terms of reducing mortality [1117]. Monk et.al in their trial administered Nebulized (interferon) IFN-β 1a.…”