Introduction: Interferons (IFNs) modulate the response of the immune system to viruses and decrease vascular leakage. IFNs have shown in-vitro activity against severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). It may improve acute respiratory distress syndrome (ARDS) complications in COVID-19. It is currently under investigation as a potential treatment for COVID-19. Objective: This review assessed the efficacy and safety of interferon and interferon combination therapy in patients with COVID-19. Methods: A systematic review and meta-analysis were performed. A search was conducted from December 1, 2019, until March 30, 2021, in MEDLINE, Cochrane CENTRAL, clinicaltrials.gov, medRxiv, ChinaXiv, and bioRxiv databases for studies and preprints. The search was conducted using the keywords “interferon” and “COVID-19” with no restrictions on language. Reference lists of selected articles were also reviewed. Randomized controlled trials on the use of interferon or interferon combination therapy compared with standard of care were included. Two reviewers independently screened, appraised, and extracted data. The risk of bias was appraised using the Evaluation of Articles on Therapy. Certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. Data were analyzed using RevMan 5.4. Results: Three RCTs with low certainty of evidence involving 4,279 hospitalized COVID 19 adult patients were included. IFN-β with or without lopinavir did not significantly reduce mortality (RR 1.12, 95% CI 0.83-1.51 and RR 1.16, 95% CI 0.96-1.39, respectively) compared with standard of care. IFN-β showed clinical response on day 14 (aOR 4.05 (95% CI, 1.42-11.55) and reduction in mortality (aOR 6.65, 95% 1.67-26.45) after adjustment for co-administration of glucocorticoid and IVIg. It also showed increased odds of recovery on day 16 (OR 3.19, 95% CI 1.24-8.24), but it did not significantly reduce the odds of developing severe disease or death (OR 0.28, 95% CI 0.07-1.08), intubation, or death (OR 0.42, 95% CI 0.09-1.83) and hospital discharge on day 16 (OR 1.63, 95% CI 0.61-4.35). Serious adverse events in patients receiving IFN-β did not differ from those receiving standard of care. Conclusion IFN-β or combined with lopinavir did not reduce mortality and progression to severe disease when added to standard of care but showed clinical response on day 16. It demonstrated a reduction in mortality in one study with small sample size. Adverse and serious adverse events were not statistically significant between groups. Its efficacy and safety should further be assessed in randomized controlled trials with higher sample sizes, without co-interventions, and during the earlier stages of COVID-19. Current use of interferon is limited only in clinical trials and compassionate use in severe to critical COVID-19.
Interferons ; COVID-19 ; SARS-CoV-2 ; Antiviral Agents