Nebulization of glutathione and N-Acetylcysteine as an adjuvant therapy for COVID-19 onset

Abstract

Ever since its emergence, the highly transmissible and debilitating coronavirus disease spread at an incredibly fast rate, causing global devastation in a matter of months. SARS-CoV-2, the novel coronavirus responsible for COVID-19, infects hosts after binding to ACE2 receptors present on cells from many structures pertaining to the respiratory, cardiac, hematological, neurological, renal and gastrointestinal systems. COVID-19, however, appears to trigger a severe cytokine storm syndrome in pulmonary structures, resulting in oxidative stress, exacerbated inflammation and alveolar injury. Due to the recent nature of this disease no treatments have shown complete efficacy and safety. More recently, however, researchers have begun to direct some attention towards GSH and NAC. These natural antioxidants play an essential role in several biological processes in the body, especially the maintenance of the redox equilibrium. In fact, many diseases appear to be strongly related to severe oxidative stress and deficiency of endogenous GSH. The high ratios of ROS over GSH, in particular, appear to reflect severity of symptoms and prolonged hospitalization of COVID-19 patients. This imbalance interferes with the body's ability to detoxify the cellular microenvironment, fold proteins, replenish antioxidant levels, maintain healthy immune responses and even modulate apoptotic events. Oral administration of GSH and NAC is convenient and safe, but they are susceptible to degradation in the digestive tract. Considering this drawback, nebulization of GSH and NAC as an adjuvant therapy may therefore be a viable alternative for the management of the early stages of COVID-19.

Evaluation the efficacy and safety of N‐acetylcysteine inhalation spray in controlling the symptoms of patients with COVID‐19: An open‐label randomized controlled clinical trial

“… 35 , 36 A high ratio of ROS to glutathione (GSH) appears to reflect the severity of symptoms and prolonged hospitalization of COVID‐19 patients. 37 NAC, which acts as a precursor of GSH inside cells, has been used in many conditions to restore or protect against GSH depletion and has a wide safety margin. Promising results have been reported in the ability of NAC to synthesize glutathione, improve the T lymphocyte proliferative response and modulate the inflammatory pathway.…”

Glutathione an Effective Adjuvant Therapy for Acute Respiratory Distress Syndrome Associated with COVID-19 Infection

“…"In inflammatory lung diseases, supplementation with exogenous sources of GSH helps to reduce the oxidant content. Oral GSH supplementation is effective in increasing plasma levels, whereas the IV route increases its levels in the pulmonary epithelial lining fluid in a short period of time" [37]. "NAC is a precursor of reduced GSH given orally NAC (600mg, bid) significantly decreases the frequency and severity of influenza" [38], and "reduces the incidences of ventilator-associated pneumonia (VAP) as well" [39].…”

Molecular Mechanisms Related to Responses to Oxidative Stress and Antioxidative Therapies in COVID-19: A Systematic Review

“…In lung diseases, for example, oral administration of GSH or nebulization with water or saline was beneficial for the patients [ 237 , 238 ]. NAC can also be administered orally, in a nebulization form or intravenously [ 239 ]. Interestingly, both orally and intravenously, high doses of NAC were effective in patients with severe symptoms of COVID-19 [ 240 ].…”