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0 0.5 1 1.5 2+ Mortality 97% Improvement Relative Risk N-acetylcysteine  Assimakopoulos et al.  LATE TREATMENT Is late treatment with N-acetylcysteine beneficial for COVID-19? Retrospective 82 patients in Greece (February - April 2021) Lower mortality with N-acetylcysteine (p=0.006) Assimakopoulos et al., Infectious Dise.., Jun 2021 Favors N-acetylcysteine Favors control

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

Assimakopoulos et al., Infectious Diseases, doi:10.1080/23744235.2021.1945675
Jun 2021  
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13th treatment shown to reduce risk in February 2021
*, now known with p = 0.000034 from 24 studies, recognized in 3 countries.
Lower risk for mortality, hospitalization, and cases.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments.
Retrospective 42 hospitalized PCR+ COVID-19 pneumonia patients treated with NAC, and a matched control group of 40 patients, showing significantly lower severe respiratory failure and significantly lower mortality with treatment. NAC 600 mg bid orally for 14 days.
risk of death, 97.1% lower, RR 0.03, p = 0.006, treatment 2 of 42 (4.8%), control 12 of 40 (30.0%), NNT 4.0, inverted to make RR<1 favor treatment, odds ratio converted to relative risk.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Assimakopoulos et al., 29 Jun 2021, retrospective, Greece, peer-reviewed, 9 authors, study period 1 February, 2021 - 30 April, 2021.
This PaperN-acetylcys..All
N-acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: a two-center retrospective cohort study
Stelios F Assimakopoulos, Diamanto Aretha, Dimitris Komninos, Dimitra Dimitropoulou, Maria Lagadinou, Lydia Leonidou, Ioanna Oikonomou, Athanasia Mouzaki, Markos Marangos
Infectious Diseases, doi:10.1080/23744235.2021.1945675
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 (PO 2 /FiO 2 <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 28days 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.
Disclosure statement The authors declare that they have no conflict of interest. ORCID Stelios F. Assimakopoulos
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De Alencar, Moreira, Muller, Double-blind, randomized, placebo-controlled trial with N-acetylcysteine for treatment of severe acute respiratory syndrome caused by COVID-19, Clin Infect Dis
De Souza, Ns, Batista, On the analysis of mortality risk factors for hospitalized COVID-19 patients: A data-driven study using the major Brazilian database, PLoS One
Harvey, Joubert, Preez, Effect of chronic N-acetyl cysteine administration on oxidative status in the presence and absence of induced oxidative stress in rat striatum, Neurochem Res
Horowitz, Freeman, Bruzzese, Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases, Respir Med Case Rep
Ibrahim, Smith, Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine, Clin Immunol
Lee, Kang, N-acetylcysteine modulates lipopolysaccharide-induced intestinal dysfunction, Sci Rep
Liu, Yao, Xu, The anti-inflammatory effects of acetaminophen and N-acetylcysteine through suppression of the NLRP3 inflammasome pathway in LPS-challenged piglet mononuclear phagocytes, Innate Immun
Mata, Morcillo, Gimeno, N-acetyl-L-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with respiratory syncytial virus (RSV), Biochem Pharmacol
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Sanguinetti, N-acetylcysteine in COPD: why, how, and when? Multidiscip, Respir Med
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Zhang, Ding, Li, Effects of N-acetylcysteine treatment in acute respiratory distress syndrome: A metaanalysis, Exp Ther Med
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Late treatment
is less effective
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