N-acetylcysteine: A rapid review of the evidence for effectiveness in treating COVID-19

Abstract

An old drug repurposed? N-acetylcysteine (NAC) was introduced in the 1960s as a mucolytic drug for chronic respiratory diseases. It has a well-established safety profile and is still commonly used orally at doses of 600mg/day as a mucolytic. In hospital settings, it is also used as an antidote for paracetamol overdose (IV formulation at doses of up to 150mg/kg) and in nebulized format in patients with acute bronchopulmonary disease (pneumonia, bronchitis, tracheobronchitis). Acetylcysteine makes bronchial mucous less viscous. In vitro, cysteine derivatives act by breaking disulphide bridges between macromolecules, which leads to a reduction in mucus viscosity. However, at higher doses (≥1200mg), acetylcysteine also acts as an antioxidant through complex mechanisms which can combat conditions of oxidative stress. Acetylcysteine is a derivative of the natural amino acid cysteine, which serves as a substrate for the synthesis of glutathione (GSH) in the body which an antioxidant effect. This reduces the formation of proinflammatory cytokines, such as IL-9 and TNF-α and also has vasodilator properties by increasing cyclic GMP levels and by contributing to the regeneration of endothelial-derived relaxing factor. It is this potential antioxidant mechanism that has sparked interest with the current COVID-19 pandemic and whether this might be useful in community settings. We therefore aimed to conduct a rapid review of NAC with specific emphasis on its potential for early administration in the community for patients at greater risk of severe COVID-19.