4-Hydroxynonenal Is Linked to Sleep and Cognitive Disturbances in Children: Once upon the Time of COVID-19

Abstract

The better prognosis of COVID-19 in children conferred a higher survival rate, but a higher prevalence of post-COVID sequalae, including insomnia and defective cognition. COVID-19 triggered oxidative stress, with hyperlipidemia correlated with susceptibility to severe COVID-19. Consequently, lipids peroxidation could be a likely candidate for disease progression and sequalae. Hence, this overview explored one of the commonly studied lipid peroxides, 4-hydroxynonenal (4-HNE), in terms of gamma-amino butyric acid (GABA) and glutamate. Higher glutamate and lower glutamine, a GABA substrate, triggered severe COVID-19. Increased glutamate and inflammatory cytokines induced GABA endocytosis, reducing the anti-inflammatory and antioxidant effects of GABA. Defective glutathione antioxidant was detected in Down syndrome, the latter was associated with severe COVID-19. Increased 4-HNE, due to consumption of electronic devices and flavors containing 1-bromopropane, was increased in inflammatory neurologic disorders. A higher hippocampal 4-HNE triggered excitotoxicity and cognitive deficits. Hippocampal inflammation and loss were also evident in COVID-19. 4-HNE might play role in disturbing sleep and cognition in children during COVID-19, a hypothesis that could be verified in future research by redeeming 4-HNE in the sputum and urine of children. Currently, supplying children with optimum dietary antioxidants, while rationalizing the use of flavors is to be encouraged.