Deficiency of Glutathione is Linked to Severe Symptoms and Deaths among COVID-19 Patients

Age and disease-related biological processes are linked with more severe cases and deaths from coronavirus SARS-CoV-2 (COVID-19), especially among persons affected with comorbidities. These symptoms make these set of persons more susceptible to infectious agents and other environmental stress features.

Among other things, associated oxidative stress and Impaired Redox Homeostasis are crucial biological progressions that contribute to higher rates of vulnerability to various environmental impairments.

This review will focus on:

• The essential roles glutathione plays in defining individual receptiveness to COVID-19 infections and its pathogenesis

• The practicability of incorporating glutathione as a solution for the possible cure and/or prevention of the SARS-CoV-2 virus.

The proposition that notable deficiencies in glutathione is the utmost conceivable cause of severe manifestations and deaths in COVID-19 patients was made on the grounds of comprehensive analysis and series of observations.

It unveils the mysteries presented by epidemiological data regarding risk factors associated with severe cases of SARS-CoV-2 and higher death rates. It also discusses feasible prospects for result-driven treatment and inhibition of COVID-19.

The rapid spread of COVID-19 across the globe has necessitated the need for identifying effective remedies for the prevention of the disease and its possible cure. Studies show that the greater majority of infected persons have asymptomatic, moderate, or mild diseases. Only 15% and 6% of patients develop severe or critical illnesses.

Higher rates of severe illnesses and deaths from the virus among persons with comorbidities and older people suggest that disease-related biological processes and age make these individuals more susceptible to the virus’s infectious agents. Associated oxidative stress and Impaired Redox Homeostasis play important roles in the biological processes that contribute to increased vulnerability.

Oxidative Stress

This is a multifaceted pathological condition that reflects the incapacity of relevant biological components to repair resulting damages or detoxify reactive intermediaries as a result of an imbalance that causes rapid production of ROS (reactive oxygen species). Studies show that ROS are closely associated with aging since they trigger immediate responses to age-inflicted damages.

Supporting studies also reveal that Associated Inflammation from excessive production of ROS due to Oxidative Stress and Decreased Antioxidant Defense facilitate pathogenesis across various chronic diseases. Some of these diseases include respiratory and cardiovascular diseases, diabetes, etc.—and they all contribute to the risk of manifesting serious symptoms and/or even death from COVID-19.

Another critical determinant for the progression of the disease and various related viral diseases is when there is virus-induced intonation of the antioxidant properties in the host. It is crucial to gain extensive understanding of the antioxidant repelling mechanisms that protect the patient from oxidative stress. Only then can we fully understand the devices that contribute to resistance or nonspecific sensitivity of the infectious mediators.

Glutathione Beneifts

Glutathione plays important roles in several metabolic pathway’s regulation and control. It is crucial for the homeostasis of the entire body system. Glutathione has the most antioxidant in terms of molecular weight. It facilitates antioxidant resistance from oxidative cell damage as a result of ROS.

Glutathione plays multifunctional and vital responsibilities in the management and detoxification of endogenous and foreign compounds, mitochondrial maintenance, immune response, protein folding, antiviral defense, rejuvenation of vitamins E and C, apoptosis, Cellular Proliferation control, and several other essential biological processes.

Despite the much said regarding glutathione’s beneficial effects on human overall health and well-being, its immense antioxidant abilities in human pathology, physiology, and clinical operations remain undervalued.

What is The Primary Cause of Serious COVID-19 Symptoms: Vitamin-D or Glutathione Deficiency?

The scientific community is currently understudying a popular hypothesis that a deficiency in VD (Vitamin-D) is linked with serious manifestations (and death in some cases) in COVID-19 patients. More studies have indicated that Glutathione levels correlate positively with active Vitamin D. Lower levels of L-Cysteine and GSH have also been reported to correlate positively with lower levels of Vitamin D (VD) and Vitamin D Binding Protein (VDBP) levels in T2D patients.

A recent study revealed that an increase in oxidative stress linked with GSH deficiency alters the regulative genes of Vitamin D. Because of this, the repressed gene lowers Vitamin D biosynthesis—which ultimately leads to an induced deficiency in Vitamin D.

However, replenishment in GSH through L-Cysteine administration positively altered epigenetic enzymes’ methyltransferases and amplified the activity of VD-metabolism genes. Overall, the study proved that Glutathione is crucial for the control of endogenous Vitamin D biosynthesis. It also demonstrated how GSH treatment is beneficial for reducing VD deficiency. Further broken down, this study indicates that Glutathione deficiency rather than VD deficiency is the more plausible factor underlying biochemical abnormalities, including lower rates of VD biosynthesis, and is, therefore, more closely linked with severe symptoms and even deaths in patients with COVID-19.

Anti-coagulant, Anti-inflammatory, and Anti-viral Properties of Glutathione

Many studies have indicated that an individual’s positive responsiveness to viral attack is linked with higher levels of Glutathione. Glutathione primarily protects the immune cells of the host using its antioxidant mechanism. It is also essential for the optimal functioning of numerous cells that make up the immune system. Notably, also, at different stages of the viral lifecycle, Glutathione hinders cell replication, thereby preventing the subsequent colossal release of harmful inflammatory cells and increased viral loads into the lungs.

The enormous antiviral properties of Glutathione were further established in an experiment at DE Flora et al. During the study, it was found that clinically apparent influenza was significantly inhibited through a six-month treatment with Preventive N-Acetylcysteine (NAC, Glutathione Precursor). It was also noted that the precursor inhibited its associated episodes, particularly in aged persons.

Additionally, pathophysiological conditions like cell injury in the lung and cases where patients with severe ARDS experienced incessant inflammations were handpicked as targets for the NAC treatment and observation.

During treatment, it was observed that ARDS patients who had deficiencies linked with lower levels of Glutathione in the alveolar fluid experienced enhanced lung cell injuries by inflammation and oxidative stress/ROS. The damages were abated by the administration of Glutathione and NAC, which would, among other things, help to increase coagulopathy in patients with COVID-19.

Kursk State Medical University’s Experiment on Redox Homeostasis in T2D Linked with Glutathione Deficiency, and how it Exacerbates COVID-19 Symptoms

In April 2020, the Kursk State Medical University accepted 4 patients from the control group. During the study, all four were diagnosed with COVID-19. Their blood samples were collected for blood sampling. Immediately after, each sample was used to measure total plasma GSH and ROS levels, respectively. All 4 patients were nonsmokers, had no chronic diseases, and were all female.

Patients with severe or moderate COVID-19 symptoms were found to have higher levels of ROS & GSH/ROS ratios and lower levels of Glutathione in plasma than patients who showed milder symptoms of COVID-19. Clearly, this indicated that Oxidative stress and Glutathione deficiency, among others, were clear signs in SARS-CoV-2 patients with more severe manifestations of the disease. Consequently, the patients with moderate-to-high levels of GSH recovered more rapidly compared to those with lower levels of Glutathione, especially those who had a very notable decrease in Glutathione levels.

Hypothesis

Endogenous Glutathione deficiency is marked as a notable factor for enhancing SARS-CoV-2-induced oxidative damage, especially in the lungs. Consequently, this leads to severe manifestations like multi-organ failure, ARDS (Acute Respiratory Distress Syndrome), and in many cases, death in patients with COVID-19. When Glutathione activity is monitored closely, results indicate that patients with higher levels of glutathione deficiency are more susceptible to uncontrolled replication of the virus. This is made apparent by a visible increase in viral load. Hence, the severity of COVID-19 clinical manifestations in patients is mainly determined by the level of impaired redox homeostasis. And, this is largely attributable to increased ROS production linked with a deficiency in Glutathione levels.

This hypothesis can be supported by the earlier experiment involving the four COVID-19 patients. It could be gathered that patients with lower Glutathione ratios and higher levels of ROS and redox status (GSH/ROS ratio) suffered more severe symptoms of the COVID-19 disease. At the same time, patients with higher levels of Glutathione and lower levels of ROS and redox status (GSH/ROS ratio) suffered less severe symptoms of the COVID-19 disease and recovered more rapidly also.

Furthermore, it can be gathered that severe and long-term manifestations of the virus infection were noticeable in patients who had higher levels of glutathione deficiency and higher ROS and redox (GSH/ROS ratio) statuses than the other COVID-19 patients. This asserts that the extent to which glutathione levels decreases correlates adversely with the COVID-19 viral replication. It also asserts that an increase in viral load aggravates oxidative impairments in the lungs.

Finally, it highlights that the COVID-19 virus cannot replicate actively where cellular glutathione levels are higher. As such, patients with higher levels of glutathione experience more trifling clinical manifestations and lesser viral loads compared to others with lower GSH levels.

Conclusion

Glutathione is doubtless a crucial player in determining the degree of manifestation of the COVID-19 virus in patients. However, its anti-viral effects are still nonspecific. As such, the renewal of glutathione reserves via Mobile I.V. Therapy in patients with SARS-CoV-2 (COVID-19) would be an excellent technique for curtailing and possibly eradicating the novel COVID-19 virus.

References

1. https://www.maxhealth.com.ng/endogenous-deficiency-of-glutathione-as-the-most-likely-cause-of-serious-manifestations-and-death-in-covid-19-patients/

2. https://www.nature.com/articles/s41598-019-51377-5.pdf?origin=ppub

3. https://www.sciencedirect.com/science/article/abs/pii/S0223523415300039

4. https://www.sciencedirect.com/science/article/abs/pii/S0026049500800773

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441751/