The role of reactive nitrogen species as biomarkers of disease severity in COVID-19

Abstract

Reactive nitrogen species (RNS) such as nitric oxide (NO) can be produced by local pulmonary cells and inflammatory cells, and they play a role in the pathogenesis of chronic pulmonary diseases and pulmonary infections. NO is an unstable compound turning to a more stable nitrite and nitrate rapidly. The objective of our study was to investigate the association between plasma nitrate+nitrite, nitrate, and nitrite levels and the severity of coronavirus disease (COVID)-19. Blood plasma samples of mild, moderate, and severe COVID-19 patients were collected from 2 different hospitals. Plasma of healthy subjects, who had never COVID-19 was used as controls (n=20 for each group). Samples were isolated by centrifugation following ultrafiltration prior to the commercial nitrate/nitrite colorimetric assay kit. Plasma nitrate+nitrite and nitrate levels, respectively, were significantly increased in severe patients (medians=34.4µM and 33.4µM), as compared to mild groups (medians=22.3µM and 20.6µM; p<0.05). In contrast, nitrite levels were significantly lower in severe patients (median= 0.8µM) than mild patients (median= 1.6µM; p<0.0001). Patients with severe disease were older (64.9 years) than the mild patients (50.6 years; p<0.05). In severe patients, age was positively correlated with nitrate+nitrite and nitrate levels, respectively (r=0.502, p=0.024; r=0.489, p=0.029). Our findings suggest that RNS may play a role in the pathogenesis of COVID-19 and that it may be considered as a marker of severity.