ABSTRACT
Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system. In contrast, interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids. To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity, we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids. Among patients receiving glucocorticoids, early interferon therapy was associated with earlier hospital discharge (adjusted HR 1.68, 95% CI 1.19-2.37) and symptom relief (adjusted HR 1.48, 95% CI 1.06-2.08), while these associations were insignificant among glucocorticoids nonusers. Early interferon therapy was also associated with lower prevalence of prolonged viral shedding (adjusted OR 0.24, 95% CI 0.10-0.57) only among glucocorticoids users. Additionally, these associations were glucocorticoid cumulative dose- and timing-dependent. These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.
Subject(s)
COVID-19 Drug Treatment , Dexamethasone/administration & dosage , Interferons/administration & dosage , SARS-CoV-2 , Adult , COVID-19/diagnosis , COVID-19/mortality , COVID-19 Nucleic Acid Testing , Dexamethasone/agonists , Drug Synergism , Female , Humans , Interferons/agonists , Male , Middle Aged , Retrospective StudiesABSTRACT
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.
Subject(s)
Antiviral Agents/administration & dosage , Betacoronavirus , Coronavirus Infections/drug therapy , Interferon-alpha/therapeutic use , Pneumonia, Viral/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , COVID-19 , Child , China/epidemiology , Cohort Studies , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Drug Therapy, Combination , Female , Hospital Mortality , Host Microbial Interactions/drug effects , Humans , Indoles/administration & dosage , Interferon alpha-2 , Interferon-alpha/administration & dosage , Length of Stay , Lopinavir/administration & dosage , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Retrospective Studies , Ritonavir/administration & dosage , SARS-CoV-2 , Treatment Outcome , Young Adult , COVID-19 Drug TreatmentABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0228391.].
ABSTRACT
BACKGROUND: The respiratory syncytial virus (RSV) is the main cause of bronchiolitis in infants and interferon (IFN) α is a commercial antiviral drug. The nebulization of IFN α1b could be a viable treatment method. In this study, the therapeutic effects and safety of IFN α1b delivery via nebulization in infant bronchiolitis were investigated in this multi-center prospective study. METHODS AND FINDINGS: Bronchiolitis patients admitted to 22 hospitals who met the inclusion criteria were enrolled and randomly allocated to four groups: control, IFN Intramuscular Injection, IFN Nebulization 1 (1 µg/kg), and IFN Nebulization 2 (2 µg/kg) groups. All patients were observed for 7 days. The therapeutic effects and safety of different IFN delivery doses and delivery modes were evaluated. Coughing severity change, as scored by the researchers and parents, between days 1 and 3 was significantly different between the IFN Nebulization 2 and control groups. Lowell wheezing score change between days 3 and 5 was significantly different between IFN Nebulization 1 and control groups. There were no significant differences among the four groups regarding the number of consecutive days with fever, three-concave sign, fatigue and sleepiness, and loss of appetite. There were no cases of severe complications, no recurrence of fever, and no regression of mental status. CONCLUSIONS: IFN-α1b could more effectively alleviate coughing and wheezing in bronchiolitis. IFN-α1b nebulization had significant advantages in shortening the duration of wheezing and alleviating coughing.
