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

FASEB J. 2020 Oct;34(10):13185-13193. doi: 10.1096/fj.202001807. Epub 2020 Aug 11.


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.

Keywords: COVID-19; N-acetyl-L-cysteine; glutathione; inflammation; oxidative stress.

Publication types

  • Review

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Angiotensin-Converting Enzyme 2 / antagonists & inhibitors
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antioxidants / therapeutic use*
  • COVID-19 Drug Treatment*
  • COVID-19* / metabolism
  • COVID-19* / pathology
  • Chemotherapy, Adjuvant
  • Humans
  • Oxidative Stress / drug effects
  • SARS-CoV-2 / metabolism*
  • Virus Internalization / drug effects*


  • Antioxidants
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Acetylcysteine