The Role of Glutathione in Prevention of COVID-19 Immunothrombosis: A Review.

Immunothrombosis has emerged as a dominant pathological process exacerbating morbidity and mortality in acute- and long-COVID-19 infections. The hypercoagulable state is due in part to immune system dysregulation, inflammation and endothelial cell damage, as well as a reduction in defense systems. One defense mechanism in particular is glutathione (GSH), a ubiquitously found antioxidant. Evidence suggests that reduction in GSH increases viral replication, pro-inflammatory cytokine release, and thrombosis, as well as decreases macrophage-mediated fibrin removal. The collection of adverse effects as a result of GSH depletion in states like COVID-19 suggest that GSH depletion is a dominant mechanism of immunothrombosis cascade. We aim to review the current literature on the influence of GSH on COVID-19 immunothrombosis pathogenesis, as well as the beneficial effects of GSH as a novel therapeutic for acute- and long-COVID-19.

Type 2 Diabetes Contributes to Altered Adaptive Immune Responses and Vascular Inflammation in Patients With SARS-CoV-2 Infection.

SARS-CoV-2, which initially emerged in November of 2019, wreaked havoc across the globe by leading to clinical acute respiratory distress syndrome and continues to evade current therapies today due to mutating strains. Diabetes mellitus is considered an important risk factor for progression to severe COVID disease and death, therefore additional research is warranted in this group. Individuals with diabetes at baseline have an underlying inflammatory state with elevated levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines, both of which cause these individuals to have higher susceptibility to SARS- CoV2 infection. The detrimental effects of SARS-CoV-2 has been attributed to its ability to induce a vast cell mediated immune response leading to a surge in the levels of pro-inflammatory cytokines. This paper will be exploring the underlying mechanisms and pathophysiology in individuals with diabetes and insulin resistance making them more prone to have worse outcomes after SARS- CoV2 infection, and to propose an adjunctive therapy to help combat the cytokine surge seen in COVID-19. It will also look at the immunomodulatory effects of glutathione, an antioxidant shown to reduce immune dysregulation in other diseases; Vitamin D, which has been shown to prevent COVID-19 patients from requiring more intensive care time possibly due to its ability to decrease the expression of certain pro-inflammatory cytokines; and steroids, which have been used as immune modulators despite their ability to exacerbate hyperglycemia.

Hyperlipidemia and Obesity's Role in Immune Dysregulation Underlying the Severity of COVID-19 Infection.

Obesity and hyperlipidemia are known to be risk factors for various pathological disorders, including various forms of infectious respiratory disease, including the current Coronavirus outbreak termed Coronavirus Disease 19 (COVID-19). This review studies the effects of hyperlipidemia and obesity on enhancing the inflammatory response seen in COVID-19 and potential therapeutic pathways related to these processes. In order to better understand the underlying processes of cytokine and chemokine-induced inflammation, we must further investigate the immunomodulatory effects of agents such as Vitamin D and the reduced form of glutathione as adjunctive therapies for COVID-19 disease.