La hiperglucemia intrahospitalaria es más importante que el antecedente de diabetes para predecir la aparición de desenlaces clínicos adversos en pacientes hospitalizados con COVID-19

Contexto: en pacientes con COVID-19, la diabetes mellitus y la hiperglucemia son condiciones prevalentes. La literatura es escasa en cuanto a la asociación de estas dos variables con desenlaces desfavorables en pacientes hospitalizados por COVID-19. Objetivo: evaluar la asociación entre hiperglucemia y la aparición de desenlaces adversos en pacientes con COVID-19. Metodología: estudio de cohorte retrospectiva en el que se evaluó la asociación entre presentar hiperglucemia con la aparición de síndrome de dificultad respiratoria aguda (SDRA), lesión renal aguda (LRA) y muerte intrahospitalaria en pacientes hospitalizados por COVID-19. Resultados: se incluyeron 408 pacientes (edad media 60.48, 58.8 % hombres, 34.1 % con diabetes, 40.4 % con hiperglucemia intrahospitalaria). La hiperglucemia se asoció de forma independiente a un mayor riesgo de SDRA (OR: 1.84, IC 95 %: 1.15 – 2.94; p=0.001), LRA (OR: 2.73; IC: 1.24–5.96; p=0.012) y muerte intrahospitalaria (OR: 2.61; IC: 1.20–5.68; p=0.015) después de controlar por variables de confusión. El antecedente de diabetes no se asoció de forma independiente con un mayor riesgo en ninguno de los tres desenlaces adversos. Conclusiones: la hiperglucemia se asocia de forma independiente con peores desenlaces en pacientes hospitalizados por COVID-19 a diferencia de la diabetes mellitus

Characterization and clinical outcomes in hospitalized patients with confirmed SARS-CoV-2 infection according to their glycemia level, with or without diabetes mellitus, at the Hospital Universitario San Ignacio during the COVID-19 pandemic.

Introducción: En pacientes con COVID-19, la diabetes mellitus y la hiperglicemia son condiciones prevalentes. La literatura es escasa en cuanto a la asociación de estas dos variables con desenlaces desfavorables en pacientes hospitalizados por SARS-CoV-2. Este estudio pretende evaluar la asociación del síndrome de dificultad respiratoria aguda (SDRA), la lesión renal aguda (LRA) y la muerte intrahospitalaria con la hiperglicemia, en comparación con pacientes normoglicémicos. Métodos: Estudio observacional analítico basado en una cohorte retrospectiva. Se llevó a cabo en un hospital universitario de referencia en Bogotá, Colombia en pacientes hospitalizados por infección por SARS-CoV-2 desde mayo hasta agosto del 2020. Se compararon los pacientes que presentaron hiperglicemia con aquellos normoglicémicos en relación a desenlaces adversos (SDRA, LRA, muerte intrahospitalaria). Resultados: La hiperglicemia se asoció a un mayor riesgo de SDRA (OR: 2.01, IC: 1.12 - 3.61; p valor = 0.020) y muerte intrahospitalaria (OR: 1.87; IC: 1.05 - 3.33; p valor = 0.032), incluso ajustando por variables significativas y relevantes. No se asoció con valores estadísticamente significativos para un mayor riesgo de LRA (OR: 1.46; IC: 0.84 - 2.25; p valor = 0.182). El antecedente de diabetes no se asoció con un mayor riesgo en ninguno de los tres desenlaces adversos. Conclusión: La hiperglicemia se asocia de forma independiente con peores desenlaces en pacientes hospitalizados por COVID-19, mientras que el antecedente de diabetes mellitus no. Lo anterior traduce a que el control metabólico tiene una mayor importancia durante la hospitalización de un paciente con infección por SARS-CoV-2.NingunaIntroduction: In patients with COVID-19, diabetes mellitus and hyperglycemia are prevalent conditions. The literature is scarce regarding the association of these two variables with unfavorable outcomes in patients hospitalized for SARS-CoV-2. This study aims to evaluate the association of acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and in-hospital death with hyperglycemia, compared with normoglycemic patients. Methods: Observational analytical study based on a retrospective cohort. It was carried out in a reference university hospital in Bogotá, Colombia in patients hospitalized for SARS-CoV-2 infection from May to August 2020. Patients with hyperglycemia were compared with those with normoglycemics in relation to adverse outcomes (ARDS, AKI, in-hospital death). Results: Hyperglycemia was associated with an increased risk of ARDS (OR: 2.01, CI: 1.12 - 3.61; p value = 0.020) and in-hospital death (OR: 1.87; CI: 1.05 - 3.33; p value = 0.032), even adjusting for by significant and relevant variables. It was not associated with statistically significant values for an increased risk of AKI (OR: 1.46; CI: 0.84 - 2.25; p value = 0.182). A history of diabetes was not associated with an increased risk in any of the three adverse outcomes. Conclusion: Hyperglycemia is independently associated with worse outcomes in patients hospitalized for COVID-19, while a history of diabetes mellitus is not. This means that metabolic control is of greater importance during the hospitalization of a patient with SARS-CoV-2 infection.Especialista en Medicina InternaEspecializaciónhttps://orcid.org/0000-0001-5955-0064https://orcid.org/0000-0002-1564-0647https://scholar.google.com/citations?user=bo6BiNEAAAAJ&hl=eshttps://scholar.google.es/citations?user=roNMmP0AAAAJ&hl=eshttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0001609740https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0001753399#Aún no se ha sometido el artículo a una revista, por lo cual se someterá en los próximos meses y se requiere el tiempo de restricción

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old