Systemic oxidative stress associates with the development of post-COVID-19 syndrome in non-hospitalized individuals

BackgroundPost-COVID-19 syndrome (PCS) remains a major health issue worldwide, while its pathophysiology is still poorly understood. Systemic oxidative stress (OS) may be involved in PCS, which is reflected by lower circulating free thiols (R–SH, sulfhydryl groups), as they are receptive to rapid oxidation by reactive species. This study aimed to investigate the longitudinal dynamics of serum R–SH after SARS-CoV-2 infection and its association with the development of PCS in individuals with mild COVID-19.MethodsBaseline serum R–SH concentrations were measured and compared between 135 non-hospitalized COVID-19 subjects and 82 healthy controls (HC). In COVID-19 subjects, serum R–SH concentrations were longitudinally measured during the acute disease phase (up to 3 weeks) and at 3, 6, and 12 months of follow-up, and their associations with relevant clinical parameters were investigated, including the development of PCS.ResultsBaseline albumin-adjusted serum R–SH were significantly reduced in non-hospitalized COVID-19 subjects as compared to HC (p = 0.041), reflecting systemic OS. In mild COVID-19 subjects, trajectories of albumin-adjusted serum R–SH levels over a course of 12 months were longitudinally associated with the future presence of PCS 18 months after initial infection (b = −9.48, p = 0.023).ConclusionNon-hospitalized individuals with COVID-19 show evidence of systemic oxidative stress, which is longitudinally associated with the development of PCS. Our results provide a rationale for future studies to further investigate the value of R–SH as a monitoring biomarker and a potential therapeutic target in the development of PCS

Serum free sulfhydryl status associates with new-onset chronic kidney disease in the general population

BACKGROUND: Serum sulfhydryl groups (R-SH, free thiols) reliably reflect the systemic redox status in health and disease. As oxidation of R-SH occurs rapidly by reactive oxygen species (ROS), oxidative stress is accompanied by reduced levels of free thiols. Oxidative stress has been implicated in the pathophysiology of chronic kidney disease (CKD), in which redox imbalance may precede the onset of CKD. Therefore, we aimed to investigate associations between serum free thiols and the risk of incident CKD as defined by renal function decline and albuminuria in a population-based cohort study. METHODS: Subjects without CKD (n = 4,745) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, a prospective, population-based cohort study in the Netherlands, were included. Baseline protein-adjusted serum free thiols were studied for their associations with the development of CKD, defined as a composite outcome of an estimated glomerular filtration rate (eGFR)  30 mg/24-h, or both. RESULTS: Median level of protein-adjusted serum free thiols at baseline was 5.14 μmol/g of protein (interquartile range [IQR]: 4.50–5.75 μmol/g) and median eGFR was 96 mL/min/1.73 m(2) [IQR: 85–106]. Protein-adjusted serum free thiols were significantly associated with incident CKD (hazard ratio [HR] per doubling 0.42 [95% confidence interval [CI]: 0.36–0.52, P 30 mg/24-h after full adjustment for confounding factors (HR per doubling 0.70 [95% CI: 0.51–0.96], P=0.028). CONCLUSION: Higher levels of serum R-SH, reflecting less oxidative stress, are associated with a decreased risk of developing CKD in subjects from the general population. This association is primarily driven by incident CKD as defined by UAE

Mild Coronavirus Disease 2019 (COVID-19) Is Marked by Systemic Oxidative Stress:A Pilot Study

Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since they are readily oxidized by reactive oxygen species (ROS). In this study, serum free thiol concentrations were measured in hospitalized and non-hospitalized patients with COVID-19 and healthy controls and their associations with relevant clinical parameters were examined. Serum free thiol concentrations were measured colorimetrically (Ellman’s method) in 29 non-hospitalized COVID-19 subjects and 30 age-, sex-, and body-mass index (BMI)-matched healthy controls and analyzed for associations with clinical and biochemical disease parameters. Additional free thiol measurements were performed on seven serum samples from COVID-19 subjects who required hospitalization to examine their correlation with disease severity. Non-hospitalized subjects with COVID-19 had significantly lower concentrations of serum free thiols compared to healthy controls (p = 0.014), indicating oxidative stress. Serum free thiols were positively associated with albumin (St. β = 0.710, p < 0.001) and inversely associated with CRP (St. β = −0.434, p = 0.027), and showed significant discriminative ability to differentiate subjects with COVID-19 from healthy controls (AUC = 0.69, p = 0.011), which was slightly higher than the discriminative performance of CRP concentrations regarding COVID-19 diagnosis (AUC = 0.66, p = 0.042). This study concludes that systemic oxidative stress is increased in patients with COVID-19 compared with healthy controls. This opens an avenue of treatment options since free thiols are amenable to therapeutic modulation