Serum nitrite and nitrate: A potential biomarker for post-covid-19 complications?

Nitric oxide (NO) plays an important role in cardiovascular and immune systems. Quantification of blood nitrite and nitrate, two relatively stable metabolites of NO (generally as NO(x)), has been acknowledged, in part, representing NO bioactivity. Dysregulation of NO(x) had been reported in SARS-CoV-2 infected populations, but whether patients recovered from COVID-19 disease present with restored NO(x) is unknown. In this study, serum NO(2)(−) and NO(3)(−) were quantified and analyzed among 109 recovered adults in comparison to a control group of 166 uninfected adults. Nitrite or nitrate levels were not significantly different among mild-, common-, severe- and critical-type patients. However, these recovered patients had dramatically lower NO(2)(−) and NO(2)(−)/NO(3)(−) than the uninfected group (p < 0.0001), with significantly higher NO(3)(−) levels (p = 0.0023) than the uninfected group. Nitrate and nitrite/nitrate were positively and negatively correlated with patient age, respectively, with age 65 being a turning point among recovered patients. These results indicate that low NO(2)(−), low NO(2)(−)/NO(3)(−) and high NO(3)(−) may be potential biomarkers of long-term poor or irreversible outcomes after SARS-CoV-2 infection. It suggests that NO metabolites might serve as a predictor to track the health status of recovered COVID-19 patients, highlighting the need to elucidate the role of NO after SARS-CoV-2 infection.