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

Abstract

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.

Glutathione deficiency in the pathogenesis of SARS-CoV-2 infection and its effects upon the host immune response in severe COVID-19 disease

“…As new variants like the omicron ( Abdool Karim and Abdool, 2021 ; Callaway and Ledford, 2021 ) and others ( Markov et al, 2022 ) appear, besides new vaccine trials continuously ongoing, physicians have been encouraged to utilize various treatments with established efficacy in similar viral or bacterial illnesses that also cause bilateral pneumonia and ARDS, as SARS-CoV-2 does. Here we present the antioxidant GSH as a potential unexplored way for further investigation as intervention for COVID-19, since GSH levels are correlated with disease severity and lung damage supporting the participation of GSH in disease outcome ( Kryukov et al, 2021 ; Singh et al, 2022 ). Enhancing GSH, mainly through NAC, GSH precursors or pro-GSH compound administration, becomes a potential treatment option for SARS-CoV-2 infection and COVID-19 disease by reducing oxidative stress and cytokine expression especially in diabetic patients at risk of more severe disease ( Singh et al, 2022 ).…”

“…Here we present the antioxidant GSH as a potential unexplored way for further investigation as intervention for COVID-19, since GSH levels are correlated with disease severity and lung damage supporting the participation of GSH in disease outcome ( Kryukov et al, 2021 ; Singh et al, 2022 ). Enhancing GSH, mainly through NAC, GSH precursors or pro-GSH compound administration, becomes a potential treatment option for SARS-CoV-2 infection and COVID-19 disease by reducing oxidative stress and cytokine expression especially in diabetic patients at risk of more severe disease ( Singh et al, 2022 ). Whey protein concentrate ameliorates lung damage and inhibits lung furin activity targeting SARS-CoV-2 S1/S2 site cleavage and SARS CoV-2 spike protein-angiotensin converting enzyme binding and could be used to protect against COVID-19 inhibiting SARS-CoV-2 cell entry ( Tufan et al, 2022 ).…”

SARS-CoV-2 coinfections with variant genomic lineages identified by multiplex fragment analysis

“…Type II diabetes is a risk factor for more severe COVID-19 ( Hartmann-Boyce et al, 2021 ). Thus, while not having underlying malignancy or managed with immunosuppressive drugs as others in this case series, this patient’s immune status was likely dysregulated due to her comorbidity which can render her more susceptible to infection ( Singh et al, 2022 ). This patient was managed without COVID-19 specific therapy and discharged 3 days later.…”

Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation

“…The demand for detailed analysis of the pathogenesis and clinical course of chronic diseases and viral diseases like COVID-19, as well as the use of efficacious therapies with minimal or no side effects are paramount. Here we present the antioxidant GSH as a potential unexplored way for further investigation as intervention to counteract inflammaging, premature inflammaging, inflammatory diseases and long-COVID-19-syndrome, since GSH levels are correlated with tissue and organ damage, disease severity and progression, and disease outcome ( 294 – 296 , 298 , 299 ). Enhancing GSH, mainly through NAC, GSH precursors rich in cysteine (whey protein, whey protein isolate rich in cysteine) or pro-GSH compound administration, becomes a potential treatment option for inflammatory diseases by reducing oxidative stress and cytokine expression especially in diabetic patients that also are at risk of more severe COVID-19 disease ( 299 ).…”

“…Here we present the antioxidant GSH as a potential unexplored way for further investigation as intervention to counteract inflammaging, premature inflammaging, inflammatory diseases and long-COVID-19-syndrome, since GSH levels are correlated with tissue and organ damage, disease severity and progression, and disease outcome ( 294 – 296 , 298 , 299 ). Enhancing GSH, mainly through NAC, GSH precursors rich in cysteine (whey protein, whey protein isolate rich in cysteine) or pro-GSH compound administration, becomes a potential treatment option for inflammatory diseases by reducing oxidative stress and cytokine expression especially in diabetic patients that also are at risk of more severe COVID-19 disease ( 299 ). GSH dysregulation might cause global immune cell autophagy decline with increased generation of proinflammatory cytokines in aging, further provoked by mitochondrial ROS signaling ( 293 ).…”