Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, USA
Vishal Deepak
Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, School of Medicine, West Virginia University, Morgantown, WV, USA
Sarah Hadique
Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, School of Medicine, West Virginia University, Morgantown, WV, USA
Drake Aesoph
WVU Cancer Institute, West Virginia University, Morgantown, WV, USA; Lane Department of Computer Science & Electrical Engineering, West Virginia University, Morgantown, WV, USA
Murugesan Velayutham
Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, USA; Department of Biochemistry and Molecular Medicine, School of Medicine, West Virginia University, Morgantown, WV, USA
Qing Ye
WVU Cancer Institute, West Virginia University, Morgantown, WV, USA; Lane Department of Computer Science & Electrical Engineering, West Virginia University, Morgantown, WV, USA
Md Habibul Hasan Mazumder
Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, USA
Sara E. Lewis
Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, USA
Vamsi Kodali
Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, USA
Anthony Roohollahi
Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, School of Medicine, West Virginia University, Morgantown, WV, USA
Nancy Lan Guo
WVU Cancer Institute, West Virginia University, Morgantown, WV, USA; Department of Occupational and Environmental Health Sciences, School of Public Health, West Virginia University, Morgantown, WV, USA
Gangqing Hu
WVU Cancer Institute, West Virginia University, Morgantown, WV, USA; Department of Microbiology, Immunology & Cell Biology, West Virginia University, Morgantown, WV, USA
Valery V. Khramtsov
Department of Biochemistry and Molecular Medicine, School of Medicine, West Virginia University, Morgantown, WV, USA
Richard J. Johnson
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
Sijin Wen
Department of Epidemiology and Biostatistics, West Virginia University, Morgantown, WV, USA
Eric E. Kelley
Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, USA
Salik Hussain
Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, USA; Department of Microbiology, Immunology & Cell Biology, West Virginia University, Morgantown, WV, USA; Corresponding author. Department of Physiology and Pharmacology, Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University, Morgantown, 26506, WV, USA.
Background: The pathophysiologic significance of redox imbalance is unquestionable as numerous reports and topic reviews indicate alterations in redox parameters during corona virus disease 2019 (COVID-19). However, a more comprehensive understanding of redox-related parameters in the context of COVID-19-mediated inflammation and pathophysiology is required. Methods: COVID-19 subjects (n = 64) and control subjects (n = 19) were enrolled, and blood was drawn within 72 h of diagnosis. Serum multiplex assays and peripheral blood mRNA sequencing was performed. Oxidant/free radical (electron paramagnetic resonance (EPR) spectroscopy, nitrite-nitrate assay) and antioxidant (ferrous reducing ability of serum assay and high-performance liquid chromatography) were performed. Multivariate analyses were performed to evaluate potential of indicated parameters to predict clinical outcome. Results: Significantly greater levels of multiple inflammatory and vascular markers were quantified in the subjects admitted to the ICU compared to non-ICU subjects. Gene set enrichment analyses indicated significant enhancement of oxidant related pathways and biochemical assays confirmed a significant increase in free radical production and uric acid reduction in COVID-19 subjects. Multivariate analyses confirmed a positive association between serum levels of VCAM-1, ICAM-1 and a negative association between the abundance of one electron oxidants (detected by ascorbate radical formation) and mortality in COVID subjects while IL-17c and TSLP levels predicted need for intensive care in COVID-19 subjects. Conclusion: Herein we demonstrate a significant redox imbalance during COVID-19 infection affirming the potential for manipulation of oxidative stress pathways as a new therapeutic strategy COVID-19. However, further work is requisite for detailed identification of oxidants (O2•-, H2O2 and/or circulating transition metals such as Fe or Cu) contributing to this imbalance to avoid the repetition of failures using non-specific antioxidant supplementation.
