Retrospective Multicenter Cohort Study Shows Early Interferon Therapy Is Associated with Favorable Clinical Responses in COVID-19 Patients

Abstract

Interferons (IFNs) are widely used in treating coronavirus disease 2019 (COVID-19) patients. However, a recent report of ACE2, the host factor mediating SARS-Cov-2 infection, identifying it as interferon-stimulated raised considerable safety concern. To examine the association between the use and timing of IFN-α2b and clinical outcomes, we analyzed in a retrospective multicenter cohort study of 446 COVID-19 patients in Hubei, China. Regression models estimated that early administration (≤5 days after admission) of IFN-α2b was associated with reduced in-hospital mortality in comparison with no admission of IFN-α2b, whereas late administration of IFN-α2b was associated with increased mortality. Among survivors, early IFN-α2b was not associated with hospital discharge or computed tomography (CT) scan improvement, whereas late IFN-α2b was associated with delayed recovery. Additionally, early IFN-α2b and umifenovir alone or together were associated with reduced mortality and accelerated recovery in comparison with treatment with lopinavir/ritonavir (LPV/r) alone. We concluded that administration of IFN-α2b during the early stage of COVID-19 could induce favorable clinical responses.

Tissue-specific and interferon-inducible expression of non-functional ACE2 through endogenous retrovirus co-option

“…Nevertheless, it is worth noting that the predicted LTR16A1-ACE2 protein product does not contain the residues required for SARS-CoV-2 spike glycoprotein binding (Shang et al, 2020) and is thus unlikely to contribute to viral spread. These results reconcile the apparent discrepancy between the interferon inducibility of ACE2 with promising data showing improved outcomes in COVID-19 following interferon treatment (Hung et al, 2020;Wang et al, 2020).…”

“…Recognition of viral products in an infected cell results in autocrine and paracrine signalling to induce an antiviral state characterized by expression of a module of interferon-stimulated genes (ISGs) that restrict viral replication and spread (Sadler and Williams, 2008;Stetson and Medzhitov, 2006). Indeed, recombinant interferon is often given as first-line therapy in viral infection (Gibbert et al, 2013) and preliminary results suggest that interferon treatment may be effective against Coronavirus disease 2019 (Hung et al, 2020;Wang et al, 2020).…”

Direct exposure to SARS-CoV-2 and cigarette smoke increases infection severity and alters the stem cell-derived airway repair response

“…This may reflect the fact that the model does not include inflammatory cells but does suggest that an intact, normal airway epithelium could function as a barrier to COVID-19 with a good innate immune response and could explain why the majority of infected individuals have mild symptoms and even asymptomatic carriage. Abrogation of SARS-CoV-2 infection with type I interferons has been reported by others in other settings (Lokugamage et al, 2020;Mantlo et al, 2020), including a small clinical trial (Wang et al, 2020).…”

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

“…While the literature surrounding this is sparse, one study included in this meta-analysis concluded that early administration of interferon-alpha-2b could induce positive outcomes in COVID-19 patients compared to standard treatment, while its late administration was associated with slower recovery. [36] It is important to highlight that this meta-analysis attempted to overcome the challenges posed by studies with insufficient power to detect an effect between JAK-inhibitor or Type I interferon treatment and clinical outcomes, as half of the included studies in this analysis utilized sample sizes less than 100. [23, 25-28, 30, 35] Nevertheless, despite the broad range of sample sizes and populations, the screening step of our analysis predominantly resulted in low effect size heterogeneity as evidenced by the I 2 statistics displayed in Figure 2 and Figure 3.…”

“…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%).…”