COVID-19-related acute respiratory distress syndrome (ARDS) is linked to mortality, primarily due to a cytokine storm, oxidative stress imbalance, and pro-thrombotic state.
Purpose
We assessed the potential association between N-acetyl-cysteine (NAC) and clinical outcomes in critically ill subjects with COVID-19-related ARDS.
Material and Methods
We included subjects with confirmed COVID-19 who were admitted to our ICU between March 1, 2020, and January 31, 2021, due to ARDS and necessitating invasive mechanical ventilation (IMV). Subjects who received standard of care (SOC) were compared with subjects who additionally received NAC 600 mg bid orally.
Results
A total of 243 subjects were included in this study. The results indicate significantly improved survival rates in the NAC plus SOC group, both in the unadjusted analysis and after adjusting for confounding factors such as ARDS severity (HR 0.48, 95% CI 0.32-0.70).
Conclusions
We found that oral administration of NAC was associated with reduced mortality in critically ill patients with COVID-19 related ARDS.
ZhengCShaoWChenXZhangBWangGZhangW. Real-world effectiveness of COVID-19 vaccines: A literature review and meta-analysis. Int J Infect Dis. 2022;114:252-260.
3.
ZhouFYuTDuR, et al.Clinical course and risk factors for mortality of adult insubjects with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet.2020;395(10229):1054-1062.
4.
HuangCWangYLiX, et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
NabLParkerEPKAndrewsCD, et al.; OpenSAFELY Collaborative. Changes in COVID-19-related mortality across key demographic and clinical subgroups in England from 2020 to 2022: A retrospective cohort study using the OpenSAFELY platform. Lancet Public Health. 2023;8(5):e364-e377.
AlbuquerqueAMEckertITramujasL, et al.Effect of tocilizumab, sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: A systematic review and meta-analysis. Clin Microbiol Infect. 2023;29(1):13-21.
9.
MilleaPJ. N-Acetylcysteine: Multiple clinical applications. Am Fam Physician. 2009;80(3):265-269.
10.
PedreBBarayeuUEzeriņaDDickTP. The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species. Pharmacol Ther. 2021;228:107916.
11.
HuiDSCLeeN. Adjunctive therapies and immunomodulating agents for severe influenza. Influenza Other Respir Viruses. 2013;7(Suppl 3):52-59.
12.
IzquierdoJLSorianoJBGonzálezY, et al.Use of N-acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19. Sci Prog. 2022;105(1):1-12.
13.
SharafkhahMAbdolrazaghnejadAZarinfarNMohammadbeigiAMassoudifarAAbaszadehS. Safety and efficacy of N-acetyl-cysteine for prophylaxis of ventilator-associated pneumonia: A randomized, double blind, placebo-controlled clinical trial. Med Gas Res. 2018;8(1):19.
14.
AssimakopoulosSFArethaDKomninosD, et al.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;53(11):847-854.
15.
ZhenJPWenFQBaiCX, et al. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): A randomised, double-blind placebo-controlled trial. Lancet Respir Med. 2014 Mar;2(3):187-194.
16.
Kordzadeh-KermaniEKhaliliHKarimzadehI. Pathogenesis, clinical manifestations and complications of coronavirus disease 2019 (COVID-19). Future Microbiol. 2020;15(13):1287-1305.
17.
The ARDS Definition Task Force. Acute respiratory distress syndrome: The Berlin definition. JAMA. 2012;307(23):2526-2533. https://doi.org/10.1001/jama.2012.5669.
18.
World medical association declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194.
19.
ElmEvAltmanDGEggerMPocockSJGøtzschePCVandenbrouckeJP. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: Guidelines for reporting observational studies. Br Med J. 2007;335(7624):806.
WeiskopfNGWengC. Methods and dimensions of electronic health record data quality assessment: Enabling reuse for clinical research. J Am Med Inform Assoc. 2013;20(1):144.
23.
WiersingaWJRhodesAChengACPeacockSJPrescottHC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): A review. JAMA. 2020;324(8):782-793.
24.
Olivas-MartínezACárdenas-FragosoJLJiménezJV, et al.In-hospital mortality from severe COVID-19 in a tertiary care center in Mexico city; causes of death, risk factors and the impact of hospital saturation. PLoS One [Internet]. 2021;16(2):e0245772.
25.
LuXMaYHeJLiYZhuHYuX. N-acetylcysteine for adults with acute respiratory distress syndrome: A meta-analysis of randomized controlled trials. Hong Kong Journal of Emergency Medicine. 2019;26(5):288-298.
26.
De AlencarJCGMoreiraCdLMüllerAD, et al.Double-blind, randomized, placebo-controlled trial with N-acetylcysteine for treatment of severe acute respiratory syndrome caused by coronavirus disease 2019 (COVID-19). Clin Infect Dis. 2021;72(11):E736-E741.
27.
PanahiYGhaneiMRahimiM, et al.Evaluation the efficacy and safety of N-acetylcysteine inhalation spray in controlling the symptoms of patients with COVID-19: An open-label randomized controlled clinical trial. J Med Virol. 2023;95(1):e28393.
28.
TaherALashgariMSedighiLRahimi-basharFPoorolajalJMehrpooyaM. A pilot study on intravenous N-acetylcysteine treatment in patients with mild-to-moderate COVID19-associated acute respiratory distress syndrome. Pharmacol Rep. 2021;73(6):1650-1659.
29.
Gamarra-MoralesYHerrera-QuintanaLMolina-LópezJ, et al.Response to intravenous N-acetylcysteine supplementation in critically ill patients with COVID-19. Nutrients. 2023;15(9):2235.
30.
ParaskevasTKantanisAKaralisI, et al.N-acetylcysteine efficacy in patients hospitalized with COVID-19 pneumonia: A systematic review and meta-analysis. Rom J Intern Med. 2023;61(1):41-52.
31.
ChenCHHungKFHuangCY, et al.Is N -acetylcysteine effective in treating patients with coronavirus disease 2019? A meta-analysis. J Chin Med Assoc. 2023;86(3):274-281.
32.
Izquierdo-AlonsoJLPérez-RialSGotera RiveraCPeces-BarbaG. N-acetylcysteine for prevention and treatment of COVID-19: Current state of evidence and future directions. J Infect Public Health. 2022;15(12):1477-1483.
33.
ShiZPuyoCA. N-Acetylcysteine to combat COVID-19. An evidence review. Ther Clin Risk Manag. 2020;16:1047-1055.
34.
De FloraSBalanskyRSebastianoAAAMaestraL. Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19. FASEB J.2020;34(10):13185-13193.
35.
BlasiFPageCRossoliniGM, et al.The effect of N-acetylcysteine on biofilms: Implications for the treatment of respiratory tract infections. Respir Med. 2016;117:190-197.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
