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 NO₂^- and NO₃^- 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 NO₂^- and NO₂^-/NO₃^- than the uninfected group (p < 0.0001), with significantly higher NO₃^- 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 NO₂^-, low NO₂^-/NO₃^- and high NO₃^- 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.