Summary of COVID-19 N-acetylcysteine studies

46 patient N-acetylcysteine late treatment RCT: 15% shorter hospitalization (p=0.001) and 51% improved recovery (p=0.001).
RCT 46 hospitalized patients with moderate COVID-19 pneumonia, 24 treated with N-acetylcysteine, showing significantly shorter hospitalization with treatment. NAC 1,200 – 1,500mg/day intravenously.
Feb 2021, Pulmonologiya, https://journal.pulmonology.ru/pulm/article/viewFile/2263/1813, https://c19p.org/gaynitdinova

2. Altay et al., Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19

305 patient N-acetylcysteine early treatment RCT: 80% lower hospitalization (p=0.25) and 83% improved recovery (p<0.0001).
RCT 304 low-risk outpatients, 229 treated with N-acetylcysteine, l-carnitine tartrate, nicotinamide riboside chloride, and serine, showing significantly faster recovery with treatment. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism were significantly improved in treated patients.
Jun 2021, Advanced Science, https://onlinelibrary.wiley.com/doi/10.1002/advs.202101222, https://c19p.org/altay

3. Assimakopoulos 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

82 patient N-acetylcysteine late treatment study: 97% lower mortality (p=0.006).
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.
Jun 2021, Infectious Diseases, https://www.tandfonline.com/doi/full/10.1080/23744235.2021.1945675, https://c19p.org/assimakopoulos

4. Avdeev et al., N-acetylcysteine for the treatment of COVID-19 among hospitalized patients

46 patient N-acetylcysteine late treatment study: 69% lower mortality (p=0.34), 77% lower ventilation (p=0.18), 77% lower ICU admission (p=0.18), and 15% shorter hospitalization (p=0.01).
Prospective study of 24 hospitalized COVID-19 patients in Russia treated with NAC, and 22 matched controls, showing significantly improved SpO2/FiO2, and significantly shorter hospitalization with treatment.
Jul 2021, J. Infection, https://www.journalofinfection.com/article/S0163-4453(21)00329-7/fulltext, https://c19p.org/avdeev

5. Galindo-Andúgar et al., Impact of N-Acetylcysteine in the mortality of patients hospitalized with COVID-19: a retrospective cohort study

378 patient N-acetylcysteine late treatment study: 43% lower mortality (p=0.05).
Retrospective 378 hospitalized patients in Spain, showing lower mortality with N-acetylcysteine treatment.
Jul 2023, Revista Clínica Española, https://www.sciencedirect.com/science/article/abs/pii/S2254887423000929, https://c19p.org/galindoandugar

6. Panahi 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

250 patient N-acetylcysteine late treatment RCT: 92% lower mortality (p<0.0001), 36% lower ICU admission (p=0.38), and 1% shorter hospitalization (p=0.81).
RCT 250 hospitalized COVID-19 patients showing reduced mortality rate and inflammatory markers with N-acetylcysteine (NAC) 400μg inhaled spray twice daily for 7 days as adjunctive treatment. There was no significant difference in hospital length of stay or ICU admission. The NAC group was older on average, while the control group had significantly lower SpO2 at baseline. 400 μg/day NAC inhaler spray for 7 days.
Dec 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.28393, https://c19p.org/panahi

7. Taher et al., A pilot study on intravenous N-Acetylcysteine treatment in patients with mild-to-moderate COVID19-associated acute respiratory distress syndrome

92 patient N-acetylcysteine late treatment RCT: 18% lower mortality (p=0.65), 14% lower ventilation (p=0.67), 20% shorter ICU admission (p=0.48), and 33% shorter hospitalization (p=0.31).
RCT 92 hospitalized patients, 47 treated with NAC, showing non-significant improvements in outcomes. IRCT20120215009014N355. NAC 40mg/kg/day intravenous for 3 days.
Jun 2021, Pharmacological Reports, https://link.springer.com/article/10.1007%2Fs43440-021-00296-2, https://c19p.org/taher

8. Atefi et al., Evaluation of the efficacy and safety of oral N‐acetylcysteine in patients with COVID‐19 receiving the routine antiviral and hydroxychloroquine protocol: A randomized controlled clinical trial

60 patient N-acetylcysteine late treatment RCT: 67% lower mortality (p=0.61).
RCT 60 hospitalized COVID-19 patients evaluating the efficacy and safety of adding oral N-acetylcysteine (NAC) at 600mg three times daily to standard antiviral treatment regimens. The NAC group showed significantly greater reduction in C-reactive protein levels, indicating reduced inflammation. Authors conclude that oral NAC may provide benefits through reducing inflammation, increasing oxygen saturation, and potentially reducing mortality when combined with certain antiviral medications in hospitalized COVID-19 patients.
Nov 2023, Immunity, Inflammation and Disease, https://onlinelibrary.wiley.com/doi/10.1002/iid3.1083, https://c19p.org/atefi

9. Huh et al., Association of previous medications with the risk of COVID-19: a nationwide claims-based study from South Korea

65,149 patient N-acetylcysteine prophylaxis study: 28% fewer cases (p<0.0001).
Retrospective database analysis of 65,149 in South Korea, showing significantly lower cases with existing N-acetylcysteine treatment. The journal version of this paper does not present the N-acetylcysteine results.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.04.20089904v2, https://c19p.org/huhnac

10. Gamarra-Morales et al., Response to Intravenous N-Acetylcysteine Supplementation in Critically Ill Patients with COVID-19

140 patient N-acetylcysteine ICU RCT: 16% lower mortality (p=0.49).
RCT 140 ICU patients in Spain, 72 treated with N-acetylcysteine (NAC). NAC patients showed improved PaO2/FiO2, CRP, D-dimer, and LDH, and there were associations between glutathione and clinical outcomes and severity biomarkers in NAC-treated patients. There was no significant difference in mortality.
May 2023, Nutrients, https://www.mdpi.com/2072-6643/15/9/2235, https://c19p.org/gamarramorales

11. Delić et al., Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial

91 patient N-acetylcysteine ICU RCT: 14% lower mortality (p=0.37).
RCT mechanically ventilated patients in Croatia, 39 treated with N-acetylcysteine and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-caused ventilator-associated pneumonia. ICU mortality results are from [repozitorij.mefst.unist.hr].
May 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/6/1118, https://c19p.org/delic

12. Rahimi et al., Efficacy of N-acetyl Cysteine in Severe COVID-19 Patients: A Randomized Controlled Phase III Clinical Trial

40 patient N-acetylcysteine ICU RCT: 33% lower mortality (p=0.19) and 8% shorter hospitalization (p=0.63).
RCT 40 ICU patients in Iran, showing lower mortality with NAC treatment, without statistical significance. Single dose intravenous NAC 300 mg/kg.
Oct 2022, Jundishapur J. Natural Pharmaceutical Products, https://brieflands.com/articles/jjnpp-129817.html, https://c19p.org/rahimi

13. Afaghi et al., N-acetylcysteine as adjuvant therapy for hospitalized Covid-19 patients: A single-center prospective cohort study

462 patient N-acetylcysteine late treatment study: 29% lower mortality (p=0.42), 41% lower ventilation (p=0.16), 20% lower ICU admission (p=0.36), and 14% shorter hospitalization (p=0.002).
Prospective study of 217 patients treated with NAC and 245 matched controls, showing improved recovery with treatment. 1500mg intravenous NAC daily.
May 2023, Caspian J Intern Med, https://caspjim.com/article-1-3389-fa.html, https://c19p.org/afaghi2

14. Pellegrini et al., A Retrospective Analysis of Outcomes Amongst COVID-19 Infected Patients with Acute Hepatitis Receiving N-Acetylcysteine Therapy in a Safety Net Hospital

864 patient N-acetylcysteine late treatment study: 52% lower mortality (p=0.0001).
Retrospective 864 hospitalized late stage COVID-19 patients in the USA, 138 receiving NAC treatment for acute hepatitis, showing lower mortality with treatment. Results are adjusted for confounders, however details are not provided.
May 2021, Gastroenterology, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8108159/, https://c19p.org/pellegrini

15. Mousapour et al., Efficacy and Safety of Acetylcysteine for the Prevention of Liver Injury in Covid-19 Intensive Care Unit Patients Under Treatment with Remdesivir: A Double-Blind, Placebo-Controlled Randomized Clinical Trial: Prevention of liver injury in severe Covid-19 pneumonia

83 patient N-acetylcysteine late treatment RCT: 2% lower mortality (p=1), 27% lower ventilation (p=0.57), 6% greater improvement (p=0.82), and 5% higher hospital discharge (p=0.8).
RCT 83 severe COVID-19 pnuemonia patients in Iran, 42 treated with acetylcysteine, showing no significant difference in clinical outcomes. All patients received remdesivir, famotidine, and vitamin C. More patients were at baseline category 4+ in the treatment group - 18 vs. 12. The trial focused on preventing liver injury in patients treated with remdesivir, showing improved AST/ALT levels with acetylcysteine.
Jun 2022, Gastroenterology and Hepatology from Bed to Bench, https://journals.sbmu.ac.ir/ghfbb/index.php/ghfbb/article/view/2565, https://c19p.org/mousapour

16. Izquierdo et al., Use of N-Acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19

19,208 patient N-acetylcysteine late treatment study: 26% lower mortality (p=0.0007).
Retrospective 19,208 COVID+ hospitalized patients in Spain, 2,071 treated with high dose NAC, showing lower mortality with treatment. In multivariable analysis, authors adjust for corticosteroids, but do not adjust for HCQ use which was also significantly more common in the NAC group. NAC 600mg every 8 hours.
Jan 2022, Science Progress, https://journals.sagepub.com/doi/10.1177/00368504221074574, https://c19p.org/izquierdo

17. Sherkawy et al., Impact of N-Acetylcysteine on Modulating Inflammation in Patients Hospitalized with Moderate COVID-19 Infections: A Prospective Randomized Trial

60 patient N-acetylcysteine late treatment RCT: 15% lower need for oxygen therapy (p=0.6) and 12% shorter hospitalization (p=0.45).
RCT 60 hospitalized patients showing that oral N-acetylcysteine (NAC) at 1800mg daily significantly decreased plasma TNF-α levels and increased glutathione peroxidase levels. The NAC group had a shorter duration of oxygen support, while there were no significant difference for length of hospital stay, need for oxygen support, or mortality. Overall, the addition of high-dose NAC reduced inflammatory markers and oxidative stress in moderate COVID-19. Limitations include the small sample size, late treatment, lack of blinding, potential overlap of treatment effect with SOC, clinical significance of biomarker results, and limited adverse event reporting.
May 2023, Archives of Pharmaceutical Sciences Ain Shams University, https://aps.journals.ekb.eg/article_306468.html, https://c19p.org/sherkawy

18. Fariña-González et al., Hourly Analysis of Mechanical Ventilation Parameters in Critically Ill Adult Covid-19 Patients: Association with Mortality

140 patient N-acetylcysteine ICU study: 39% lower mortality (p=0.08).
Retrospective 140 mechanically ventilated patients in Spain, showing lower mortality with acetylcysteine treatment in unadjusted results, not reaching statistical significance.
May 2022, J. Intensive Care Medicine, http://journals.sagepub.com/doi/10.1177/08850666221105423, https://c19p.org/farinagonzalez

19. Ignatova et al., Therapeutic possibilities of using an expectorant mucolytic agent with antioxidant properties in COVID-19 infection

111 patient N-acetylcysteine early treatment study: 20% shorter hospitalization (p=0.05).
Retrospective 111 patients with moderate COVID-19 pneumonia, 56 treated with NAC, showing shorter hospitalization time with treatment. NAC 1200mg daily intravenous, divided into two doses.
Nov 2021, Russian Medical Inquiry, https://www.rusmedreview.com/upload/iblock/b14/473-478.pdf, https://c19p.org/ignatova

20. Pourhoseingholi et al., Case Characteristics, Clinical Data, And Outcomes of Hospitalized COVID-19 Patients In Qom Province, Iran: A Prospective Cohort Study

2,468 patient N-acetylcysteine late treatment study: 11% lower mortality (p=0.43).
Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing no significant difference with NAC treatment. IR.MUQ.REC.1399.013.
May 2021, Research Square, https://www.researchsquare.com/article/rs-365321/v2, https://c19p.org/pourhoseingholina

21. Çavuş et al., Kritik COVID-19 hastalarında kullanılan N-asetilsisteinin(NAC) klinik bulgulara, inflamatuar parametrelere böbrek fonksiyonlarına olan etkileri

190 patient N-acetylcysteine ICU study: 13% higher mortality (p=0.47), 20% higher ventilation (p=0.25), 12% shorter ICU admission (p=0.58), and 13% shorter hospitalization (p=0.09).
Retrospective 190 critical COVID-19 patients in Turkey, showing no significant differences with N-acetylcysteine treatment in unadjusted results with no baseline details. NAC 2400mg/day.
Oct 2022, Aksaray Üniversitesi Tıp Bilimleri Dergisi, https://dergipark.org.tr/en/pub/asujms/issue/73171/1062868, https://c19p.org/cavus

22. Ramadhan et al., The Effects of N-Acetylcysteine as Adjuvant Therapy To Reduce TNF-Α Level And Increase SPO2/FIO2 Ratio In Improving Hypoxemia In COVID-19 Patients

91 patient N-acetylcysteine late treatment study: 135% higher mortality (p=0.68).
Prospective study with 75 NAC patients and 16 control patients, showing no significant difference in mortality.
Dec 2021, Indonesian J. Tropical and Infectious Disease, https://www.e-journal.unair.ac.id/IJTID/article/view/30874, https://c19p.org/ramadhan

23. Faverio et al., Impact of N-acetyl-l-cysteine on SARS-CoV-2 pneumonia and its sequelae: results from a large cohort study

901 patient N-acetylcysteine late treatment study: 19% higher mortality (p=0.33), 34% higher ICU admission (p=0.08), and 1% higher hospital discharge (p=0.94).
Retrospective 1,083 consecutive hospitalized COVID patients in Italy, showing no significant differences with NAC treatment. The number of patients transferred to another facility exceeds the number of deaths, which may significantly affect results.
Dec 2021, ERJ Open Research, https://openres.ersjournals.com/content/8/1/00542-2021, https://c19p.org/faverio

24. de Alencar 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)

135 patient N-acetylcysteine late treatment RCT: 3% higher mortality (p=0.94), 16% higher ventilation (p=0.64), 9% lower ICU admission (p=0.65), and 10% longer hospitalization (p=0.87).
RCT 135 severe stage patients in Brazil, showing no significant differences. NAC 21g (~300mg/kg) for 20 hours. U1111-1250-356 [ensaiosclinicos.gov.br].
Sep 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/72/11/e736/5910353, https://c19p.org/dealencar

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