N-acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: a two-center retrospective cohort study

Infect Dis (Lond). 2021 Nov;53(11):847-854. doi: 10.1080/23744235.2021.1945675. Epub 2021 Jun 29.


Background: N-acetyl-cysteine (NAC) has been previously shown to exert beneficial effects in diverse respiratory diseases, through antioxidant and anti-inflammatory actions. Our aim was to evaluate NAC potential impact in hospitalised patients with COVID-19 pneumonia, in terms of progression to severe respiratory failure (SRF) and mortality.

Patients and methods: This retrospective, two-centre cohort study included consecutive patients hospitalised with moderate or severe COVID-19 pneumonia. Patients who received standard of care were compared with patients who additionally received NAC 600 mg bid orally for 14 days. Patients' clinical course was recorded regarding (i) the development of SRF (PO2/FiO2 <150) requiring mechanical ventilation support and (ii) mortality at 14 and 28 days.

Results: A total of 82 patients were included, 42 in the NAC group and 40 in the control group. Treatment with oral NAC led to significantly lower rates of progression to SRF as compared to the control group (p < .01). Patients in the NAC group presented significantly lower 14- and 28-day mortality as compared to controls (p < .001 and p < .01 respectively). NAC treatment significantly reduced 14- and 28-day mortality in patients with severe disease (p < .001, respectively). NAC improved over time the PO2/FiO2 ratio and decreased the white blood cell, CRP, D-dimers and LDH levels. In the multivariable logistic regression analysis, non-severe illness and NAC administration were independent predictors of 28-days survival.

Conclusion: Oral NAC administration (1200 mg/d) in patients with COVID-19 pneumonia reduces the risk for mechanical ventilation and mortality. Our findings need to be confirmed by properly designed prospective clinical trials.

Keywords: ARDS; COVID-19; N-acetyl-cysteine; antioxidant; mortality; pneumonia.

MeSH terms

  • Acetylcysteine / therapeutic use
  • COVID-19*
  • Cohort Studies
  • Humans
  • Prospective Studies
  • Respiration, Artificial*
  • Retrospective Studies
  • SARS-CoV-2


  • Acetylcysteine