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.