Peer-review started: December 29, 2020
First decision: January 18, 2021
Revised: January 23, 2021
Accepted: March 12, 2021
Article in press: March 12, 2021
Published online: March 25, 2021
Processing time: 76 Days and 14.4 Hours
N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. 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.
Core Tip: N-acetylcysteine is a long known antioxidant that is currently best studied for its use as an antidote for acetaminophen overdose. Its off-label use in various diseases, such as chronic respiratory disease, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza, has shown promising results, as have recent clinical trials investigating the potential benefits of N-acetylcysteine in patients with coronavirus disease 2019.