The Impact of Serum Levels of Reactive Oxygen and Nitrogen Species on the Disease Severity of COVID-19

Int J Mol Sci. 2023 May 18;24(10):8973. doi: 10.3390/ijms24108973.

Abstract

Elucidation of the redox pathways in severe coronavirus disease 2019 (COVID-19) might aid in the treatment and management of the disease. However, the roles of individual reactive oxygen species (ROS) and individual reactive nitrogen species (RNS) in COVID-19 severity have not been studied to date. The main objective of this research was to assess the levels of individual ROS and RNS in the sera of COVID-19 patients. The roles of individual ROS and RNS in COVID-19 severity and their usefulness as potential disease severity biomarkers were also clarified for the first time. The current case-control study enrolled 110 COVID-19-positive patients and 50 healthy controls of both genders. The serum levels of three individual RNS (nitric oxide (NO•), nitrogen dioxide (ONO-), and peroxynitrite (ONOO-)) and four ROS (superoxide anion (O2•-), hydroxyl radical (•OH), singlet oxygen (1O2), and hydrogen peroxide (H2O2)) were measured. All subjects underwent thorough clinical and routine laboratory evaluations. The main biochemical markers for disease severity were measured and correlated with the ROS and RNS levels, and they included tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), the neutrophil-to-lymphocyte ratio (NLR), and angiotensin-converting enzyme 2 (ACE2). The results indicated that the serum levels of individual ROS and RNS were significantly higher in COVID-19 patients than in healthy subjects. The correlations between the serum levels of ROS and RNS and the biochemical markers ranged from moderate to very strongly positive. Moreover, significantly elevated serum levels of ROS and RNS were observed in intensive care unit (ICU) patients compared with non-ICU patients. Thus, ROS and RNS concentrations in serum can be used as biomarkers to track the prognosis of COVID-19. This investigation demonstrated that oxidative and nitrative stress play a role in the etiology of COVID-19 and contribute to disease severity; thus, ROS and RNS are probable innovative targets in COVID-19 therapeutics.

Keywords: COVID-19; angiotensin-converting enzyme 2; interleukin-6; reactive nitrogen species; reactive oxygen species; tumor necrosis factor-alpha.

MeSH terms

  • Biomarkers
  • COVID-19*
  • Case-Control Studies
  • Female
  • Humans
  • Hydrogen Peroxide / metabolism
  • Male
  • Nitric Oxide
  • Oxygen*
  • Patient Acuity
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • Oxygen
  • Hydrogen Peroxide
  • Reactive Nitrogen Species
  • Nitric Oxide
  • Biomarkers

Grants and funding

This research was funded by the authors.