Systemic oxidative stress associates with the development of post-COVID-19 syndrome in non-hospitalized individuals
Larissa E. Vlaming-van Eijk,
Marian L.C. Bulthuis,
Bernardina T.F. van der Gun,
Karin I. Wold,
Alida C.M. Veloo,
María F. Vincenti González,
Martin H. de Borst,
Wilfred F.A. den Dunnen,
Jan-Luuk Hillebrands,
Harry van Goor,
Adriana Tami,
Arno R. Bourgonje
Affiliations
Larissa E. Vlaming-van Eijk
University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands
Marian L.C. Bulthuis
University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands
Bernardina T.F. van der Gun
University of Groningen, University Medical Center Groningen, Department of Medical Microbiology and Infection Prevention, Groningen, the Netherlands
Karin I. Wold
University of Groningen, University Medical Center Groningen, Department of Medical Microbiology and Infection Prevention, Groningen, the Netherlands
Alida C.M. Veloo
University of Groningen, University Medical Center Groningen, Department of Medical Microbiology and Infection Prevention, Groningen, the Netherlands
María F. Vincenti González
University of Groningen, University Medical Center Groningen, Department of Medical Microbiology and Infection Prevention, Groningen, the Netherlands
Martin H. de Borst
University of Groningen, University Medical Center Groningen, Department of Internal Medicine, Division of Nephrology, Groningen, the Netherlands
Wilfred F.A. den Dunnen
University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands
Jan-Luuk Hillebrands
University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands
Harry van Goor
University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands
Adriana Tami
University of Groningen, University Medical Center Groningen, Department of Medical Microbiology and Infection Prevention, Groningen, the Netherlands
Arno R. Bourgonje
University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, the Netherlands; The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Corresponding author. P.O. Box 30.001, 9700 RB, Groningen, the Netherlands.
Background: Post-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. Methods: Baseline 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. Results: Baseline 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). Conclusion: Non-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.
