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 > 68.4 μmol/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.