The Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients

Background Data:

Glutathione is a small protein composed of three amino acids – cysteine, glutamic acid, and glycine. It exerts a central role in cellular metabolism and is intricately involved in many important body processes including:

  • Acting as the cell’s major intracellular antioxidant and also recycles other antioxidants such as vitamins C and E.
  • Exerting antiviral actions and modulating the immune response by enhancing its effectiveness when immune function is low and bringing it back into balance when the immune system is overactive.
  • Being the body’s most effective detoxifier, binding to undesirable toxins, pollutants, cancer-causing chemicals, heavy metals, and drug metabolites and excreting them through the urine or feces.
  • Assisting in the regulation of vital cellular functions, such as the synthesis and repair of DNA, the synthesis of proteins, and the activation and regulation of enzymes.
  • Playing a critical role in the function of mitochondria (the energy producing compartments in cells).

New Data:

In a very detailed review article, a hypothesis was expressed that the higher rates of serious illness and death from COVID-19 infection among older people and those who have comorbidities is due to their lower glutathione status. In fact, on the basis of an exhaustive literature analysis and observations it was offered that a deficiency of glutathione may be the most important underlying factor in leading to serious COVID-19 infection.

Being older is a well-recognized risk factor for severe illness, complications, and death from COVID-19 infection. There is a lot of data from animal and human studies indicate that the levels of glutathione progressively decline with aging. Lower glutathione levels make cells in the elderly more susceptible to oxidative damage compared to younger individuals or healthier older folks. Low glutathione levels in the elderly impairs the immune system as well as the protective barriers in the respiratory tract and gastrointestinal tract. The same impairments exist in these comorbidities associated with COVID-19:

  • Chronic kidney disease
  • COPD (chronic obstructive pulmonary disease)
  • Immunocompromised state (weakened immune system) from solid organ transplant
  • Obesity (body mass index [BMI] of 30 or higher)
  • Serious heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies
  • Sickle cell disease
  • Type 2 diabetes mellitus

Not only was the hypothesis that glutathione deficiency is the most plausible explanation for serious manifestation and death in COVID-19 patients presented, the potential role of glutathione and compounds that boost glutathione were discussed as real opportunities for effective treatment and prevention of the disease. Several studies have shown that higher levels of glutathione improves an individual’s responsiveness to viral infections. While glutathione is known to protect immune cells and enhance certain antiviral immune functions, there is also evidence that glutathione inhibits replication of various viruses at different stages of the viral life cycle, and this antiviral property of glutathione seems to prevent increased viral loads and the subsequent massive release of inflammatory cells into the lung (“cytokine storm”).

The author of the review had some important conclusions:

Since the antiviral effect of glutathione is nonspecific, there is reason to believe that glutathione is also active against SARS- CoV-2. Therefore, restoration of glutathione levels in COVID- 19 patients would be a promising approach for the manage- ment of the novel coronavirus SARS-CoV-2. Notably, long-term oral administration of N-acetylcysteine has already been tested as an effective preventive measure against respiratory viral infections. N-Acetylcysteine is widely available, safe, and cheap and could be used in an “off-label” manner. Moreover, parenteral injection of NAC or reduced glutathione (GSH is more bioavailable than NAC) could be an efficient therapy for COVID-19 patients with serious illness. Horowitz et al. just published a paper confirming this hypothesis: the authors reported the efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia.

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