RESUMEN
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.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Dexametasona/administración & dosificación , Interferones/administración & dosificación , SARS-CoV-2 , Adulto , COVID-19/diagnóstico , COVID-19/mortalidad , Prueba de Ácido Nucleico para COVID-19 , Dexametasona/agonistas , Sinergismo Farmacológico , Femenino , Humanos , Interferones/agonistas , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Antivirales/administración & dosificación , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , COVID-19 , Niño , China/epidemiología , Estudios de Cohortes , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/mortalidad , Quimioterapia Combinada , Femenino , Mortalidad Hospitalaria , Interacciones Microbiota-Huesped/efectos de los fármacos , Humanos , Indoles/administración & dosificación , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Tiempo de Internación , Lopinavir/administración & dosificación , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/mortalidad , Estudios Retrospectivos , Ritonavir/administración & dosificación , SARS-CoV-2 , Resultado del Tratamiento , Adulto Joven , Tratamiento Farmacológico de COVID-19RESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0228391.].
RESUMEN
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.