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

Abstract

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 representing NO bioactivity partially. 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 a potential biomarker 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.

Hyperglycemia and Loss of Redox Homeostasis in COVID-19 Patients

“…Hypoxia also increases the presence of protons, in a similar way as in a neutral or acidic pH, compromising the stability of ONOO − and decomposing peroxynitrous acid to form nitrates (NO 3 − ) and NO 2 − [54]. ONOO − causes the irreversible process of nitration of tyrosines in proteins, it oxidizes the thiol groups in them [56] and it also lowers the H 2 S concentration. In this sense, H 2 S is a potent gasotransmitter that is decreased in COVID-19 patients [57].…”

Plasma Endothelial and Oxidative Stress Biomarkers Associated with Late Mortality in Hospitalized COVID-19 Patients

“…Both are evaluated in vivo with serum NO metabolites; nitrite and nitrate. Patients who recovered from COVID-19 showed lower nitrite and nitrite/nitrate ratio and higher nitrate levels than uninfected subjects [ 32 ]. COVID-19 causes SARS, where nitrate+nitrite concentrations were higher in patients with SARS who died, as reported by Sittipunt et al [ 33 ].…”

Nitric Oxide: The Missing Factor in COVID-19 Severity?

“…Wang et al measured the nitrate and nitrite levels of 109 recovered adult COVID-19 patients 4 months after recovery and compared them to those of 166 uninfected adults. Lower nitrite and nitrite/nitrate, and higher nitrate levels were found among the recovered patients, indicating according to the authors long-lasting eNOS damage after COVID-19 infection [ 96 ]. Fasted nitrate levels have been used as an indicator of eNOS function, but since the work of Lauer et al, multiple studies have found that circulating nitrite and nitrate/nitrite ratios are a more accurate indication of eNOS dysfunction; thus, the lower nitrite levels in both studies are a clear indicator of eNOS dysfunction [ 97 ].…”