Review: Improving Therapeutics for COVID-19 with Glutathione-boosting Treatments that Improve Immune Responses and Reduce the Severity of Viral Infections

Glutathione-boosting treatments have been shown to enhance immune responses and reduce the severity of influenza, coronavirus, HIV and other viral infections. Such viral infections markedly increase the production of Reactive Oxygen Species (ROS) and deplete cysteine and critical antioxidants, including reduced glutathione (GSH). These viruses use depletion of GSH to create an oxidized environment needed for viral replication/assembly and evading the host immune system. High levels of reduced glutathione in antigen presenting cells is critical for mounting an adaptive immune response to viral infections and for avoiding inflammatory cytokine responses. SARS CoV-1 up-regulates TGF-β1, which increases ROS, depletes glutathione and lowers substrate and enzyme needed for glutathione synthesis. Demographic groups with highest susceptibility to SARS-CoV-2 infection (e.g. the elderly; diabetics and African-Americans) have lower levels of Glutathione, lower amino acid substrate and/or critical enzyme needed to synthesize glutathione. Increased susceptibility of the elderly, diabetics and African-Americans to SARS-CoV-2 may in part be due to a reduced ability to maintain high GSH and redox status during viral infection. This paper reviews a substantial body of evidence that Glutathione-boosting supplements including N-Acetyl Cysteine (NAC), Alpha Lipoic Acid (ALA) and Liposomal Reduced Glutathione have beneficial effects in combating viral disruption of redox status and immune responses in animal models and in humans. Glutathione-boosting treatments improve immune responses, as well as reduce viral replication, inflammatory cytokines and/or severity of viral infections, including HIV and even Influenza in the elderly. The potential for glutathione-boosting supplements to reduce risks of severe COVID-19 induced cytokine storms and disease in susceptible populations is addressed. Clinical trials are needed to determine if the severity of COVID-19 is reduced from onset of symptoms by: combined oral treatment with up to 2400 mg/day NAC and 1200 mg/day ALA; or with NAC, ALA and 2000 mg/day oral Liposomal Reduced Glutathione; versus a placebo control.