High serum nitrates levels in non-survivor COVID-19 patients / Altas concentraciones séricas de nitratos en pacientes fallecidos por COVID-19

Objective: Higher blood nitrate and nitrite levels have been found in coronavirus disease 2019 (COVID-19) patients than in healthy subjects. The present study explores the potential association between serum nitrate levels and mortality in COVID-19 patients. Design: A prospective observation study was carried out. Setting: Eight Intensive Care Units (ICUs) from 6 hospitals in the Canary Islands (Spain). Patients: COVID-19 patients admitted to the ICU. Interventions: Determination of serum nitrate levels at ICU admission. Main variable of interest: Mortality at 30 days. Results: Non-surviving (n=11) compared to surviving patients (n=42) showed higher APACHE-II (p<0.001) and SOFA scores (p=0.004), and higher serum nitrate levels (p=0.001). Logistic regression analyses showed serum nitrate levels to be associated to 30-day mortality after controlling for SOFA (OR=1.021; 95%CI=1.006–1.036; p=0.01) or APACHE-II (OR=1.023; 95%CI=1.006–1.041; p=0.01). There were no differences in the area under the curve (AUC) for mortality prediction by serum nitrate levels (AUC=83%; 95%CI=73–92%; p<0.001), APACHE II (AUC=85%; 95%CI=75–96%; p<0.001) and SOFA (AUC=78%; 95%CI=63–92%; p=0.005) based on the DeLong method. The Kaplan–Meier analysis found patients with serum nitrates levels>68.4μmol/l to have a higher mortality rate (hazard ratio=138.8; 95%CI=22.3–863.9; p<0.001). Conclusions: The main novel finding was the association between serum nitrate levels and mortality in COVID-19 patients controlling for the SOFA or APACHE-II scores, though larger studies are needed to confirm this observation (AU)

Objetivo: Se han encontrado niveles más elevados de nitratos en la sangre de pacientes con enfermedad del coronavirus 2019 (COVID-19) que en sujetos sanos. Por lo tanto, el objetivo de estudio consistió en explorar la posible asociación entre los niveles séricos de nitratos y la mortalidad de pacientes por COVID-19. Diseño: Estudio observacional y prospectivo. Ámbito: Ocho unidades de cuidados intensivos (UCI) de 6 hospitales de las Islas Canarias (España). Pacientes: Pacientes COVID-19 ingresados en la UCI. Intervenciones: Se midieron los niveles séricos de nitratos al ingreso en la UCI. Variable de interés principal: Mortalidad a los 30 días. Resultados: Los pacientes fallecidos (n=11) comparados con los supervivientes (n=42) presentaron mayores APACHE-II (p<0,001), SOFA (p=0,004) y niveles séricos de nitratos (p=0,001). Los análisis de regresión logística mostraron una asociación entre los niveles séricos de nitratos al ingreso en la UCI y la mortalidad a los 30 días controlando por SOFA (OR:1.021; IC 95%:1.006-1.036; p=0,01) o APACHE-II (OR:1.023; IC 95%:1.006-1.041; p=0,01). No encontramos diferencias en el área bajo la curva (ABC) para la predicción de mortalidad entre los niveles séricos de nitratos (ABC:83%; IC 95%:73-92%; p<0,001), APACHE-II (ABC:85%; IC 95%:75-96%; p<0,001) y SOFA (ABC:78%; IC 95%:63-92%; p=0,005) con el método de DeLong. El análisis de Kaplan-Meier mostró que los pacientes que tenían niveles séricos de nitratos al ingreso en la UCI>68,4μmol/l presentaban mayor riesgo de fallecer (hazard ratio:138,8; IC 95%:22,3-863,9; p<0,001). Conclusiones: El principal nuevo hallazgo fue la asociación entre los niveles séricos de nitratos y la mortalidad de pacientes COVID-19 controlando por SOFA o APACHE-II; pero estudios de mayor tamaño muestral son necesarios para confirmar este resultado (AU)

High serum nitrates levels in non-survivor COVID-19 patients.

OBJECTIVE: Higher blood nitrate and nitrite levels have been found in coronavirus disease 2019 (COVID-19) patients than in healthy subjects. The present study explores the potential association between serum nitrate levels and mortality in COVID-19 patients. DESIGN: A prospective observation study was carried out. SETTING: Eight Intensive Care Units (ICUs) from 6 hospitals in the Canary Islands (Spain). PATIENTS: COVID-19 patients admitted to the ICU. INTERVENTIONS: Determination of serum nitrate levels at ICU admission. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: Non-surviving (n=11) compared to surviving patients (n=42) showed higher APACHE-II (p<0.001) and SOFA scores (p=0.004), and higher serum nitrate levels (p=0.001). Logistic regression analyses showed serum nitrate levels to be associated to 30-day mortality after controlling for SOFA (OR=1.021; 95%CI=1.006-1.036; p=0.01) or APACHE-II (OR=1.023; 95%CI=1.006-1.041; p=0.01). There were no differences in the area under the curve (AUC) for mortality prediction by serum nitrate levels (AUC=83%; 95%CI=73-92%; p<0.001), APACHE II (AUC=85%; 95%CI=75-96%; p<0.001) and SOFA (AUC=78%; 95%CI=63-92%; p=0.005) based on the DeLong method. The Kaplan-Meier analysis found patients with serum nitrates levels>68.4µmol/l to have a higher mortality rate (hazard ratio=138.8; 95%CI=22.3-863.9; p<0.001). CONCLUSIONS: The main novel finding was the association between serum nitrate levels and mortality in COVID-19 patients controlling for the SOFA or APACHE-II scores, though larger studies are needed to confirm this observation.

[HLA genetic polymorphisms and prognosis of patients with COVID-19]. / Polimorfismos genéticos de los HLA y pronóstico de pacientes con COVID-19.

OBJECTIVE: Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients. DESIGN: Observational and prospective study. SETTING: Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain). PATIENTS: COVID-19 patients admitted in ICU and healthy subjects. INTERVENTIONS: Determination of HLA genetic polymorphisms. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p=0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p=0.02) and HLA-C*16 (p=0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR=7.693; 95% CI=1.063-55.650; p=0.04) or APACHE-II (OR=11.858; 95% CI=1.524-92.273; p=0.02), the allele HLA-C*01 after controlling for SOFA (OR=11.182; 95% CI=1.053-118.700; p=0.04) or APACHE-II (OR=17.604; 95% CI=1.629-190.211; p=0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR=9.963; 95% CI=1.235-80.358; p=0.03). CONCLUSIONS: The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn.

HLA genetic polymorphisms and prognosis of patients with COVID-19.

Objective: Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients. Design: Observational and prospective study. Setting: Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain). Patients: COVID-19 patients admitted in ICU and healthy subjects. Interventions: Determination of HLA genetic polymorphisms. Main variable of interest: Mortality at 30 days. Results: A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p = 0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p = 0.02) and HLA-C*16 (p = 0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR = 7.693; 95% CI = 1.063-55.650; p = 0.04) or APACHE-II (OR = 11.858; 95% CI = 1.524-92.273; p = 0.02), the allele HLA-C*01 after controlling for SOFA (OR = 11.182; 95% CI = 1.053-118.700; p = 0.04) or APACHE-II (OR = 17.604; 95% CI = 1.629-190.211; p = 0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR = 9.963; 95% CI = 1.235-80.358; p = 0.03). Conclusions: The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn.

Objetivo: Diferentes polimorfismos genéticos de los antígenos leucocitarios humanos (HLA) están asociados con el riesgo y el pronóstico de enfermedades autoinmunes e infecciosas. Los objetivos de estudio fueron determinar si existe una asociación entre polimorfismos genéticos de HLA y la susceptibilidad y mortalidad de pacientes con la enfermedad del coronavirus 2019 (COVID-19). Diseño: Estudio observacional y prospectivo. Ámbito: Ocho unidades de cuidados intensivos (UCI) de 6 hospitales de las Islas Canarias (España). Pacientes: Pacientes COVID-19 ingresados en la UCI y sujetos sanos. Intervenciones: Se determinaron los polimorfismos genéticos de los HLA. Variable de interés principal: Mortalidad a los 30 días. Resultados: Se incluyeron 3.886 sujetos sanos y 72 pacientes COVID-19 (10 fallecidos y 62 supervivientes a 30 días). Encontramos una tendencia a una mayor frecuencia de los alelos HLA-A*32 (p = 0,004) en sujetos sanos que en pacientes COVID-19, y de los alelos HLA-B*39 (p = 0,02) y HLA-C*16 (p = 0,02) en pacientes COVID-19 que en sujetos sanos; sin embargo, no fueron significativos al corregir por comparaciones múltiples. En la regresión logística encontramos que la presencia de ciertos alelos estuvo asociada con mayor mortalidad, como el alelo HLA-A*11 controlando por SOFA (OR= 7.693; IC del 95%= 1.063-55.650; p = 0,04) o APACHE-II (OR= 11.858; IC del 95%= 1.524-92.273; p = 0,02), el alelo HLA-C*01 controlando por SOFA (OR= 11.182; IC del 95%= 1.053-118.700; p = 0,04) o APACHE-II (OR= 17.604; IC del 95%= 1.629-190.211; p = 0,02) y el alelo HLA-DQB1*04 controlando por SOFA (OR= 9.963; IC del 95%= 1.235-80.358; p = 0,03). Conclusiones: Los nuevos hallazgos de nuestro preliminar estudio de pequeño tamaño muestral fueron que determinados polimorfismos genéticos de los HLA podrían estar asociados con la mortalidad de pacientes COVID-19; sin embargo, son necesarios estudios de mayor tamaño muestral para concluirlo definitivamente.

High serum nitrates levels in non-survivor COVID-19 patients.

OBJECTIVE: Higher blood nitrate and nitrite levels have been found in coronavirus disease 2019 (COVID-19) patients than in healthy subjects. The present study explores the potential association between serum nitrate levels and mortality in COVID-19 patients. DESIGN: A prospective observation study was carried out. SETTING: Eight Intensive Care Units (ICUs) from 6 hospitals in the Canary Islands (Spain). PATIENTS: COVID-19 patients admitted to the ICU. INTERVENTIONS: Determination of serum nitrate levels at ICU admission. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: Non-surviving (n=11) compared to surviving patients (n=42) showed higher APACHE-II (p<0.001) and SOFA scores (p=0.004), and higher serum nitrate levels (p=0.001). Logistic regression analyses showed serum nitrate levels to be associated to 30-day mortality after controlling for SOFA (OR=1.021; 95%CI=1.006-1.036; p=0.01) or APACHE-II (OR=1.023; 95%CI=1.006-1.041; p=0.01). There were no differences in the area under the curve (AUC) for mortality prediction by serum nitrate levels (AUC=83%; 95%CI=73-92%; p<0.001), APACHE II (AUC=85%; 95%CI=75-96%; p<0.001) and SOFA (AUC=78%; 95%CI=63-92%; p=0.005) based on the DeLong method. The Kaplan-Meier analysis found patients with serum nitrates levels>68.4µmol/l to have a higher mortality rate (hazard ratio=138.8; 95%CI=22.3-863.9; p<0.001). CONCLUSIONS: The main novel finding was the association between serum nitrate levels and mortality in COVID-19 patients controlling for the SOFA or APACHE-II scores, though larger studies are needed to confirm this observation.