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.

Keywords: RNA virus; anti-retroviral agents; anti-viral immunity; cytokine storm syndrome; infectious disease; respiratory medicine; viral infection.

Graphical abstract

Figure 1

Sampling Strategy of COVID-19 Patient Records

Figure 2

Early IFN Therapy Associated with Reduced In-Hospital Mortality but not with Early Recovery of COVID-19 (A) Bar graph depicting initiation timing of IFN therapy among analyzed patients. Initiation of IFN therapy within first 5 days of hospitalization was empirically deemed early. (B) Kaplan-Meier curve of in-hospital mortality in patients stratified by IFN therapy status (Log-rank test of all curves, p < 0.001). (C and D) Cumulative event curves of hospital discharge (Log-rank test of all curves, p = 0.018) (C) and CT scan improvement (Log-rank test of all curves, p = 0.003) (D).

Figure 3

IFN-Based Therapies Associated with More Favorable Clinical Response than LPV/r in COVID-19 (A and B) Cumulative event curves of hospital discharge (Log-rank test of all curves, p < 0.001) (A) and CT scan improvement (Log-rank test of all curves, p < 0.001) (B) in survivors, excluding those that received late IFN therapy stratified by treatments. (C and D) Cumulative event curves of hospital discharge (Log-rank test, p < 0.001) (C) and CT scan improvement (Log-rank test, p < 0.001) (D) in survivors, excluding those that received late IFN therapy stratified by LPV/r use. (E) Kaplan-Meier curves of in-hospital mortality in all patients, excluding those that received late IFN therapy stratified by treatments (Log-rank test of all curves, p = 0.011).