**2.11 Interferons**

Studies with interferon-β had shown its activity against MERS. Most studies involved combination therapy with lopinavir/ritonavir or ribavirin. However, there was no concrete evidence showing its effect on SARS- CoV-2 in-vitro and the lack of clinical trials precluded the justification for its use in Covid-19 patients and hence there are no recommendations regarding its use [69]. In a study, it was shown that early triple antiviral therapy with lopinavir/ritonavir, ribavirin, and interferon beta-1b was safe and superior to lopinavir-ritonavir combinations alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19 [70]. In a trial utilizing interferon β-1a, clinical response time was not significantly different between interferon and the control groups (9.7 ± 5.8 versus 8.3 ± 4.9days, respectively, P = 0.95). On day 14, 66.7% versus 43.6% of patients in the interferon group and the control group respectively was discharged (OR, 2.5; 95% CI, 1.05–6.37). The 28-day overall mortality was significantly less in the interferon than the control group (19% versus 43.6%, respectively, P = 0.015). Early administration significantly decreased mortality (OR, 13.5; 95% CI, 1.5–1.18) [71]. Another trial testing interferon β-1b showed its effectiveness in reducing the clinical improvement time without any serious adverse events in severe COVID-19 patients. ICU admission and invasive ventilation need also decreased following administration of interferon β-1b [72]. The Lancet Respiratory Medicine showed the results of an RCT of nebulized interferon beta-1a in 101 adults admitted to the hospital with COVID-19. It demonstrated better odds of clinical improvement than placebo (OR 2·32 [95% CI 1·07–5·04]; p = 0·03). No significant difference was there in the hospital discharge odds by day 28 [73]. Recently, the SOLIDARITY trial also showed no benefit of interferon therapy [74].
