Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19

• Published in: The FASEB journal Vol. 34; no. 10; p. 13185
• Main Authors: De Flora, Silvio, Balansky, Roumen, La Maestra, Sebastiano
• Format: Journal Article
• Language: English
• Published: United States 01.10.2020
• Subjects: Acetylcysteine - therapeutic use; Angiotensin-Converting Enzyme 2 - antagonists & inhibitors; Angiotensin-Converting Enzyme 2 - metabolism; Antioxidants - therapeutic use; Chemotherapy, Adjuvant; COVID-19 - drug therapy; COVID-19 - metabolism; COVID-19 - pathology; Humans; Oxidative Stress - drug effects; SARS-CoV-2 - metabolism; Virus Internalization - drug effects; COVID-19; inflammation; glutathione; oxidative stress; N-acetyl-L-cysteine
• ISSN: 1530-6860
• DOI: 10.1096/fj.202001807

COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID-19 patients. N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving GSH depletion and oxidative stress. At very high doses, NAC is also used as an antidote against paracetamol intoxication. 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.