Endothelial dysfunction, oxidative stress and low-grade endotoxemia in COVID-19 patients hospitalised in medical wards

Background: Endothelial dysfunction, assessed by flow-mediated dilation (FMD), is related to poor prognosis in patients with COVID-19 pneumonia (CP). In this study, we explored the interplay among FMD, NADPH oxidase type 2 (NOX-2) and lipopolysaccharides (LPS) in hospitalised patients with CP, community acquired pneumonia (CAP) and controls (CT). Methods: We enrolled 20 consecutive patients with CP, 20 hospitalised patients with CAP and 20 CT matched for sex, age, and main cardiovascular risk factors. In all subjects we performed FMD and collected blood samples to analyse markers of oxidative stress (soluble Nox2-derived peptide (sNOX2-dp), hydrogen peroxide breakdown activity (HBA), nitric oxide (NO), hydrogen peroxide (H2O2)), inflammation (TNF-& alpha; and IL-6), LPS and zonulin levels. Results: Compared with controls, CP had significant higher values of LPS, sNOX-2-dp, H2O2,TNF-& alpha;, IL-6 and zonulin; conversely FMD, HBA and NO bioavailability were significantly lower in CP. Compared to CAP patients, CP had significantly higher levels of sNOX2-dp, H2O2, TNF-& alpha;, IL-6, LPS, zonulin and lower HBA. Simple linear regression analysis showed that FMD inversely correlated with sNOX2-dp, H2O2, TNF-& alpha;, IL-6, LPS and zonulin; conversely FMD was directly correlated with NO bioavailability and HBA. Multiple linear regression analysis highlighted LPS as the only predictor of FMD. Conclusion: This study shows that patients with COVID-19 have low-grade endotoxemia that could activate NOX-2, generating increased oxidative stress and endothelial dysfunction.

Automated summary

This study found that patients with COVID-19 have endothelial dysfunction, which is related to poor prognosis. The study also investigated the interplay among flow-mediated dilation (FMD), NADPH oxidase type 2 (NOX-2), and lipopolysaccharides (LPS) in hospitalized patients, including those with COVID-19 pneumonia (CP), community-acquired pneumonia (CAP), and controls (CT). The results showed that COVID-19 patients had higher levels of LPS, sNOX2-dp, H2O2, TNF-α, IL-6, and zonulin, while FMD, HBA, and NO bioavailability were lower. Linear regression analysis demonstrated a negative correlation between FMD and sNOX2-dp, H2O2, TNF-α, IL-6, LPS, and zonulin, and a positive correlation with NO bioavailability and HBA. Multiple linear regression analysis identified LPS as the only predictor of FMD.