Therapeutic effectiveness of interferon-alpha 2b against COVID-19: the Cuban experience

Abstract

Background Effective therapies are needed to control the SARS-Cov-2 infection pandemic and reduce mortality associated with COVID-19. Several clinical studies have provided evidence for the antiviral effects of type I interferons (IFNs) in patients with respiratory coronaviruses. This study assessed the therapeutic efficacy of IFN-alpha 2b in patients infected with SARS-CoV-2 during the first month after the outbreak began in Cuba. Method This multicenter prospective observational study was conducted in 16 hospitals in 8 Cuban provinces. Participants were patients with confirmed SARS-CoV-2 infection detected from throat swab specimens by real time RT-PCR who gave informed consent and had no contraindications for IFN treatment. Patients received therapy as per the Cuban COVID protocol, that included a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular administration of IFN-alpha 2b (Heberon Alpha R, Center for Genetic Engineering and Biotechnology, Havana), 3 times per week, for 2 weeks. The primary endpoint was the proportion of patients discharged from hospital (without clinical and radiological symptoms and non-detectable virus by RT-PCR). The secondary endpoint was the case fatality rate (CFR), defined as the number of confirmed deaths divided by the number of confirmed cases. Results From March 11th to April 14th, 814 patients were confirmed SARS-CoV-2 positive in Cuba, 761 (93.4%) were treated with Heberon Alpha R and 53 received the approved protocol without IFN treatment. The proportion of fully recovered patients was higher in the IFN-treated compared with non-IFN treated group (95.4% vs 26.1%, p<0.01). The CFR for all patients was 2.95%, and for those patients who received IFN-alpha 2b the CFR was reduce to 0.92. The estimated global CFR is 6.34% and 4.05% for the Americas reported by WHO and PAHO, respectively. In this study, 82 patients (10.1%) required intensive care and, of these, 42 (5.5%) were treated with IFN. Conclusions This report provides preliminary evidence for the therapeutic effectiveness of IFN alpha-2b for COVID-19 and suggests that the use of Heberon Alpha R may contribute to complete recovery.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version)

“…One prospective cohort study [64] enrolled 814 patients with COVID-19 in Cuba. Seven hundred sixty-one were treated with the IFN-α2b (intramuscular injection, 3 million IU 3 times per week, for 2 weeks) combined with the approved protocol (included lopinavir-ritonavir and chloroquine), 53 received the protocol without IFN treatment.…”

JAK-Inhibitor and Type I Interferon Ability to Produce Favorable Clinical Outcomes in COVID-19 Patients: A Systematic Review and Meta-Analysis

“…In addition, two studies consistently demonstrated opposite associations between Type I interferon therapy and clinical outcomes, [30,33] when comparing summary statistics and other included studies. [28,29,31,34,35] Heterogeneity among populations studied may play a role in the disparate individual results, as half of these studies were conducted in China, one was conducted in Iran, five were conducted in Western Europe, and one was conducted in Cuba. Other irreconcilable factors that may have influenced patient outcomes included individual study exclusion criterion, as well as the dosage and delivery method of the intervention.…”

“…Meta-analysis of 3 sets of studies with 990, 454, and 1480 patients receiving Type I interferon therapy revealed that there were no significant associations between receiving Type I interferon therapy, compared to standard of care, and ICU admittance, requiring mechanical ventilation, or developing a severe or critical case of COVID-19, respectively (p>0.05; Figure 3B; Figure 3C; Figure 3D). [28][29][30][31][32][33][34][35][36] The analyses included 97, 167, and 537 control patients, respectively. The data exhibited very high heterogeneity in cases of ICU admittance and disease severity (both I 2 >90%), but relatively low in the case of mechanical ventilation (I 2 =12%).…”

Pharmacological Treatments of Covid-19 – A Review

“…The proportion of fully recovered patients was respectively as 95.4% versus 26.1%, p<0.01). The CFR was 0.92 versus 2.95% [97]. Another exploratory study reported IFN treatment on accelerated viral clearance and reductions in circulating IL-6 and CRP levels among 77 patients after adjusting for age, sex, and co-morbidities [98].…”