Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases

Horowitz, Richard; Freeman, Phyllis R.; Bruzzese, James

doi:10.1016/j.rmcr.2020.101063

Cited by 163 publications

(172 citation statements)

References 74 publications

(86 reference statements)

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“…Oral administration of GSH is more expensive than supplements with cysteine and glycine, and its systemic bioavailability may be poor due to degradation in the gut; therefore, its suitability for use on a large population could be limited. Interestingly, a case report study has shown that the repeated use of both 2000 mg of oral administration and intravenous injection of glutathione was effective in relieving the severe respiratory symptoms of COVID-19, showing for the first time the efficacy of this antioxidant therapy for COVID-19 [102].…”

Section: Treatment With Gsh and Thiolsmentioning

confidence: 99%

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

2020

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The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease has a mild or even asymptomatic progression. A common denominator in all conditions associated with COVID-19 appears to be the impaired redox homeostasis responsible for reactive oxygen species (ROS) accumulation; therefore, levels of glutathione (GSH), the key anti-oxidant guardian in all tissues, could be critical in extinguishing the exacerbated inflammation that triggers organ failure in COVID-19. The present review provides a biochemical investigation of the mechanisms leading to deadly inflammation in severe COVID-19, counterbalanced by GSH. The pathways competing for GSH are described to illustrate the events concurring to cause a depletion of endogenous GSH stocks. Drawing on evidence from literature that demonstrates the reduced levels of GSH in the main conditions clinically associated with severe disease, we highlight the relevance of restoring GSH levels in the attempt to protect the most vulnerable subjects from severe symptoms of COVID-19. Finally, we discuss the current data about the feasibility of increasing GSH levels, which could be used to prevent and subdue the disease.

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Section: Treatment With Gsh and Thiolsmentioning

confidence: 99%

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

2020

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“…Most (but not all) of the biological roles of Se, both as selenocysteine in selenoproteins, and as redox-active Se-containing metabolites, involve interactions with cysteine thiols and disulfides in proteins and peptides, and their various oxidized forms. Like Se, the essential antioxidant and free radical scavenger glutathione (GSH), a tripeptide thiol, has also proven to be an important factor in various viral infections, particularly in HIV/AIDS, as reviewed in section 2.1.2. of Taylor ( 6 ), and most recently, in COVID-19 ( 7 , 8 ). Given their intertwined biochemical roles, there are likely to be common factors and mechanisms underlying the therapeutic importance of Se and GSH in viral infections.…”

Section: Introductionmentioning

confidence: 99%

Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis?

Taylor

Radding

2020

Front. Nutr.

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Glutathione peroxidases (GPX), a family of antioxidant selenoenzymes, functionally link selenium and glutathione, which both show correlations with clinical outcomes in COVID-19. Thus, it is highly significant that cytosolic GPX1 has been shown to interact with an inactive C145A mutant of M pro , the main cysteine protease of SARS-CoV-2, but not with catalytically active wild-type M pro . This seemingly anomalous result is what might be expected if GPX1 is a substrate for the active protease, leading to its fragmentation. We show that the GPX1 active site sequence is substantially similar to a known M pro cleavage site, and is identified as a potential cysteine protease site by the Procleave algorithm. Proteolytic knockdown of GPX1 is highly consistent with previously documented effects of recombinant SARS-CoV M pro in transfected cells, including increased reactive oxygen species and NF-κB activation. Because NF-κB in turn activates many pro-inflammatory cytokines, this mechanism could contribute to increased inflammation and cytokine storms observed in COVID-19. Using web-based protease cleavage site prediction tools, we show that M pro may be targeting not only GPX1, but several other selenoproteins including SELENOF and thioredoxin reductase 1, as well as glutamate-cysteine ligase, the rate-limiting enzyme for glutathione synthesis. This hypothesized proteolytic knockdown of components of both the thioredoxin and glutaredoxin systems is consistent with a viral strategy to inhibit DNA synthesis, to increase the pool of ribonucleotides for RNA synthesis, thereby enhancing virion production. The resulting “collateral damage” of increased oxidative stress and inflammation would be exacerbated by dietary deficiencies of selenium and glutathione precursors.

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“…The endemic infection spread rapidly without sparing a continent and became a global pandemic ( 11 ). The mortality rate of critically sick patients is high, approximately 49-61.5 % or higher, 79% ( 7 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Cytokine storm induced new onset depression in patients with COVID-19. A new look into the association between depression and cytokines -two case reports

Alpert

Begun

Garren

et al. 2020

Brain, Behavior, & Immunity - Health

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Background Depression appears to be a common complication in patients during and post–COVID-19 infection. Understanding the mechanism of action of cytokines such as interleukin-6, interleukin-10 and others in depression and in cytokine storm syndrome, the core component of COVID- 19, could shine a new light on future treatment options for both disorders. Objective This review demonstrates the role of interleukins in COVID-19 pathogenesis and their role in depression. Results We described cases we have treated as an example for the dual role interleukins have in COVID-19 infection and depression and reviewed approximately 70 articles focusing on the role of interleukins in cytokine storm syndrome and depression. Conclusion This review highlights the key features of cytokines in both diseases. As the scientific community has more time to recover and process the effect of the current pandemic, we believe that additional research will pave the way to diverse pathways to treat depression in these patient and others.

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Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases

Cited by 163 publications

References 74 publications

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis?

Cytokine storm induced new onset depression in patients with COVID-19. A new look into the association between depression and cytokines -two case reports

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