ABSTRACT
Hypothesis: Optimizing glutathione status in symptomatic COVID-19 patients may prevent the development of more severe aspects of the disease. During the inflammatory phase in symptomatic COVID-19 patients the oxidant stress has the potential to be massive. The observed cytokine storm is a source of free radicals that can cause a major oxidant stress, which in turn leads to a self-fueling vicious cycle of cytokine-mediated oxidant injury. SARS-CoV-2 virus uses the angiotensin-converting enzyme 2 (ACE2) receptor to invade the cell. ACE2 activation induces an antioxidant response by activating Nrf2 and inhibiting NFκB. Nrf2 promotes production of glutathione that could reduce NFκB activation and consequently reduce generation of cytokines. Could the glutathione status of individuals account for the unexplained variability in clinical presentations of COVID-19? Elderly subjects are the hardest hit by COVID-19. Beyond their comorbidities, they exhibit a slower protein metabolism explaining the lower level of plasma glutathione reported in this population. Obesity is an aggravating factor observed in deaths occurring in elderly and younger COVID-19 patients. Beyond the comorbidities such as diabetes, hypertension, cardiovascular diseases associated with obesity, the metabolic syndrome reported in these subjects is associated with lower glutathione levels and oxidant stress. Optimizing glutathione levels should be considered in symptomatic subjects with proven COVID-19. Following the action of endogenous gamma-glutamyltranspeptidase, plasma glutathione is an efficient source of substrates for de novo tissue synthesis of glutathione. The injection of glutathione might be contemplated in these patients. Although injectable glutathione is not yet available on the market, N-acetylcysteine (NAC) could be considered. It is an existing and approved form of bioavailable cysteine limiting substrate for glutathione synthesis. In a recent review on NAC in COVID-19, the Center for Evidence Based Medicine (University of Oxford, UK) concluded that preclinical data suggest that NAC may have a purpose in viral respiratory infections. doi: xxxxx