N-Acetylcysteine and Other Sulfur-Donors as a Preventative and Adjunct Therapy for COVID-19

Abstract

The airway epithelial glycocalyx plays an important role in preventing severe acute respiratory syndrome coronavirus 2 entry into the epithelial cells, while the endothelial glycocalyx contributes to vascular permeability and tone, as well as modulating immune, inflammatory, and coagulation responses. With ample evidence in the scientific literature that coronavirus disease 2019 (COVID-19) is related to epithelial and endothelial dysfunction, preserving the glycocalyx should be the main focus of any COVID-19 treatment protocol. The most studied functional unit of the glycocalyx is the glycosaminoglycan heparan sulfate, where the degree and position of the sulfate groups determine the biological activity. N-acetylcysteine (NAC) and other sulfur donors contribute to the inorganic sulfate pool, the rate-limiting molecule in sulfation. NAC is not only a precursor to glutathione but also converts to hydrogen sulfide, inorganic sulfate, taurine, Coenzyme A, and albumin. By optimising inorganic sulfate availability, and therefore sulfation, it is proposed that COVID-19 can be prevented or at least most of the symptoms attenuated. A comprehensive COVID-19 treatment protocol is needed to preserve the glycocalyx in both the prevention and treatment of COVID-19. The use of NAC at a dosage of 600 mg bid for the prevention of COVID-19 is proposed, but a higher dosage of NAC (1200 mg bid) should be administered upon the first onset of symptoms. In the severe to critically ill, it is advised that IV NAC should be administered immediately upon hospital admission, and in the late stage of the disease, IV sodium thiosulfate should be considered. Doxycycline as a protease inhibitor will prevent shedding and further degradation of the glycocalyx.

A Randomized Clinical Trial Comparing N-acetylcysteine and Bromhexine in Outpatients

“…Similarly, the study conducted by Taher et al supports the bene cial effect of NAC in treating Covid-19 patients [19]. Moreover, the investigation conducted by Du Preez HN et al produced results consistent with our study, demonstrating positive outcomes with the use of NAC [20]. Although these studies provide encouraging ndings, it is important to continue exploring and validating the e cacy of NAC as a treatment for Covid-19.…”

Does the use of cysteine-rich whey protein supplements (Inmunocal®) improve the health well-being of COVID-19 patients? A qualitative study

“…A recent review has posited that N-acetylcysteine supplementation is a potential tool against SARS-CoV-2 and may suppress viral replication [24]. However, clinical trials demonstrating its potential benefits have yet to be evidenced, but several studies have posited that its use alone, in various doses or in combination with other antiviral agents or vitamins (i.e., vitamin D) can dramatically reduce the rate of hospitalization, mechanical ventilation, and mortality [23][24][25]. In view of this growing interest, interestingly our results have shown that there is an improvement in symptoms and physical well-being following its adjunctive use in the management of COVID-19.…”

“…P.O. ), (100 mg/kg/day IV), and multiple organ failure (150 mg/kg/day IV) [24]. Currently, there are no studies from reliable sources that reveal the exact dosage of the supplement Inmunocal®, neither for patients with COVID-19 nor for the general population; however, there are images and information from consultants of this product recommending the use of two sachets in healthy patients and four or more in patients with a chronic disease (i.e., patients with mild pain can consume 20 grams of Inmunocal® and in severe cases, the dosage could be increased to 30 grams) [26].…”

Overview and New Insights into the Metabolic Syndrome: Risk Factors and Emerging Variables in the Development of Type 2 Diabetes and Cerebrocardiovascular Disease

“…In order to supplement the restoration of the dysfunctional, attenuated, or loss of the ecGCx as occurs in sepsis, COVID-19, neuroinflammation and neurodegenerative disease, and T2DM, one would need to make provisions for an adequate supply of sulfur compounds and/or thiols [ 151 ]. From this standpoint, sulodexide (SDX), a heparin sulfate-like compound resistant to degradation by heparanase, accelerated ecGCx regeneration in vitro and in vivo [ 169 ], sodium thiosulfate (STS) [ 136 , 170 ], and n-acetyl-cysteine (NAC) [ 171 ] are approved and available for clinical use and have been recently utilized in the treatment of the T2DM and sepsis, glia-mediated neuroinflammation in neurodegenerative disease, and COVID-19.…”