Viral infections can cause so much inflammation that the body doesn't have enough glutathione to protect the lungs, which leads to difficulty breathing. Glutathione is safe and relatively inexpensive and can be tried at home.
Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19.
"Thiols block the angiotensin-converting enzyme 2 thereby hampering
penetration of SARS-CoV-2 into cells. Based on a broad range of
antioxidant and anti-inflammatory mechanisms, which are herein reviewed,
the oral administration of NAC is likely to attenuate the risk of
developing COVID-19, as it was previously demonstrated for influenza and
influenza-like illnesses. Moreover, high-dose intravenous NAC may be
expected to play an adjuvant role in the treatment of severe COVID-19
cases and in the control of its lethal complications, also including
pulmonary and cardiovascular adverse events. "
The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19
"The outlined overview describes how SARS-CoV-2 can unbalance a high
activity of the renin-angiotensin system in the lung via ACE2 downregulation,
followed by free radical mediated inflammation, and unveils the protective role
of GSH; this biochemical approach to COVID-19 disease opens novel avenues for
further investigation aimed at understanding the involved molecular
mechanisms."
"Several pieces of evidence reported in our biochemical analysis suggest
that low levels of GSH could be one of the major causes of the excessive
inflammatory response linked to severe COVID-19 symptoms and indicate that
increasing body GSH could reduce the number of symptomatic patients. Future
clinical studies investigating the levels of GSH in COVID-19 patients may be
the starting point to explore this possibility."
N-acetylcysteine for the treatment of COVID-19 among hospitalized patients
"Overall, our study demonstrated that NAC therapy provided a significant
improvement in oxygenation parameters and reduction in CRP, NEWS2 scale,
and length of hospitalization in hospitalized patients with COVID-19.
These results need to be confirmed with further randomized prospective
trials in a larger cohort."
Could glutathione depletion
be the Trojan horse of COVID-19 mortality?
"In particular, this review provided an in-depth discussion regarding the
pathophysiology by which COVID-19 leads to GSH depletion, tissue damage, and
acute respiratory distress syndrome. In addition, the current review
demonstrated how GSH depletion could result in failure of the immune system and
rendering the end organs vulnerable to damage from the oxidative stress."
Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19
"It has been proven efficacious in off-label uses, such as in respiratory
diseases, heart disease, cancer, human immunodeficiency virus infection, and
seasonal influenza. Clinical trials have recently shown that NAC's capacity to
replenish glutathione stores may significantly improve coronavirus disease 2019
(COVID-19) outcomes, especially in high risk individuals. Interestingly,
individuals with glucose 6-phosphate dehydrogenase deficiency have been shown
to experience even greater benefit. The same study has concluded that NAC's
ability to mitigate the impact of the cytokine storm and prevent elevation of
liver enzymes, C-reactive protein, and ferritin is associated with higher
success rates weaning from the ventilator and return to normal function in
COVID-19 patients. Considering the background knowledge of biochemistry,
current uses of NAC in clinical practice, and newly acquired evidence on its
potential efficacy against COVID-19, it is worthwhile to investigate further
whether this agent can be used as a treatment or adjuvant for COVID-19."
Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine
"Glucose 6-phosphate dehydrogenase (G6PD) deficiency facilitates human
coronavirus infection due to glutathione depletion. G6PD deficiency may
especially predispose to hemolysis upon coronavirus disease-2019 (COVID-19)
infection when employing pro-oxidant therapy. However, glutathione depletion is
reversible by N-acetylcysteine (NAC) administration. We describe a severe case
of COVID-19 infection in a G6PD-deficient patient treated with
hydroxychloroquine who benefited from intravenous (IV) NAC beyond reversal of
hemolysis. NAC blocked hemolysis and elevation of liver enzymes, C-reactive
protein (CRP), and ferritin and allowed removal from respirator and veno-venous
extracorporeal membrane oxygenator and full recovery of the G6PD-deficient
patient. NAC was also administered to 9 additional respirator-dependent
COVID-19-infected patients without G6PD deficiency. NAC elicited clinical
improvement and markedly reduced CRP in all patients and ferritin in 9/10
patients. NAC mechanism of action may involve the blockade of viral infection
and the ensuing cytokine storm that warrant follow-up confirmatory studies in
the setting of controlled clinical trials."
N-Acetylcysteine to Combat COVID-19: An Evidence Review
N-acetylcysteine (NAC) is inexpensive, has very low toxicity, has been
FDA approved for many years, and has the potential to improve
therapeutic strategies for COVID-19. NAC administered intravenously,
orally, or inhaled, may suppress SARS-CoV-2 replication and may improve
outcomes if used timely. Potential therapeutic benefits of NAC include,
extracellularly scavenging ROS radicals, replenishing intracellular GSH,
suppression of cytokine storm, and T cell protection, thus mitigating
inflammation and tissue injury. NAC administration in combination with
other antiviral agents may dramatically reduce hospital admission rate,
mechanical ventilation and mortality.
N-Acetylcysteine as Adjuvant Therapy for COVID-19 – A Perspective on the Current State of the Evidence
"In view of the widespread recognition of the safety and efficacy of
N-acetylcysteine in numerous diseases over several decades, the aroused
scientific interest has prompted the evaluation of its efficacy in
COVID-19 clinical trials. As such, it opens a window for drug discovery
with additional advantages, comprising the known pharmacological and
human safety profiles. Advances in nanoparticle design are foreseen to
have an impact on optimizing drug delivery and targeted activity of
N-acetylcysteine in coronavirus disease. Currently, there is some
evidence supporting the use of N-acetylcysteine as an adjunctive therapy
for COVID-19. Further studies are warranted to design a formulation
with increased bioavailability or target-oriented delivery, ascertain
optimal dosage and route of administration, and conduct well-controlled,
adequately powered, randomized clinical trials to determine the safety
and efficacy of N-acetylcysteine in patients with COVID-19."
N-Acetylcysteine: A potential therapeutic agent for SARS-CoV-2
"Lower cellular redox status, which leads to pro-inflammatory states mediated by TNF-ɑ is also potentially implicated. In vivo, in vitro,
and human clinical trials have demonstrated N-acetylcysteine (NAC) as
an effective method of improving redox status, especially when under
oxidative stress. In human clinical trials, NAC has been used to
replenish glutathione stores and increase the proliferative response of T
cells. NAC has also been shown to inhibit the NLRP3 inflammasome
pathway (IL1β and IL18) in vitro, and decrease plasma TNF-ɑ in
human clinical trials. Mediation of the viral load could occur through
NAC’s ability to increase cellular redox status via maximizing the rate
limiting step of glutathione synthesis, and thereby potentially
decreasing the effects of virally induced oxidative stress and cell
death. We hypothesize that NAC could act as a potential therapeutic
agent in the treatment of COVID-19 through a variety of potential
mechanisms, including increasing glutathione, improving T cell response,
and modulating inflammation."
