Participation of Nitrogen Oxide and Its Metabolites in the Genesis of Hyperimmune Inflammation in COVID-19

Abstract

Despite the success in the tactics of treating COVID-19, there are many unexplored issues related to the development and progression of the process in the lungs, brain, and other organs, as well as the role of individual elements, in particular, nitric oxide (NO), and in the pathogenesis of organ damage. Based on the analyzed literature data, we considered a possible pathophysiological mechanism of action of NO and its derivatives in COVID-19. It can be noted that hyperimmune systemic inflammation and “cytokine storm” are enhanced by the production of NO, products of its oxidation (“nitrosative stress”). It is noted in the work that as a result of the oxidation of NO, a large amount of the toxic compound peroxynitrite is formed, which is a powerful proinflammatory agent. Its presence significantly damages the endothelium of the vascular walls and also oxidizes lipids, hemoglobin, myoglobin, and cytochrome, binds SH-groups of proteins, and damages DNA in the target cells. This is confirmed by the picture of the vessels of the lungs on computed tomography and the data of biochemical studies. In case of peroxynitrite overproduction, inhibition of the synthesis of NO and its metabolic products seems to be justified. Another aspect considered in this work is the mechanism of damage by the virus to the central and peripheral nervous system, which remains poorly understood but may be important in understanding the consequences, as well as predicting brain functions in persons who have undergone COVID-19. According to the analyzed literature, it can be concluded that brain damage is possible due to the direct effect of the virus on the peripheral nerves and central structures, and indirectly through the effect on the endothelium of cerebral vessels. Disturbances in the central nervous regulation of immune responses may be associated with the insufficient function of the acetylcholine anti-inflammatory system. It is proposed to further study several approaches to influence various links of NO exchange, which are of interest for theoretical and practical medicine.

Oxidative stress and COVID-19-associated neuronal dysfunction: mechanisms and therapeutic implications

“… Paraoxonase COVID-19 PON1 (serum paraoxonase 1) has been demonstrated to increase protein levels from non-severe to severe patients [74] . Peroxynitrite The overproduction of peroxynitrite exacerbates the severity of the COVID-19 [102] . ROS In vitro studies have found that Covid-19 infection increases ROS production in human promonocyte cells and various mammalian cells [103] .…”

Significance of nitrosative stress and glycoxidation products in the diagnosis of COVID-19

“…COVID-19, an infection caused by the severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2), can be asymptomatic or can produce mild or severe symptoms that can lead to life-threatening multiorgan failure in patients 1 , 2 . The severity of symptoms is evaluated with the use of diagnostic scales, including the Modified Early Warning Score (MEWS) 3 , 4 An infection with the SARS-CoV-2 virus triggers excessive production of reactive oxygen species (ROS) 5 and reactive nitrogen species (RNS) 6 , which enhances protein glycoxidation 7 , 8 . In patients who had experienced severe symptoms, as well as mild and moderate symptoms of COVID-19, these processes are intensified and can lead to various complications 7 .…”

Hydroxytyrosol and Arginine as Antioxidant, Anti-Inflammatory and Immunostimulant Dietary Supplements for COVID-19 and Long COVID

“…Secondly, the European Food Safety Authority has approved HXT as a means of protecting the cardiovascular system. From a theoretical point of view, we study the interaction between HXT and arginine to stop the production of harmful peroxynitrite, which is responsible for pneumonia and numerous organ failures associated with COVID-19 [13].…”