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0 0.5 1 1.5 2+ Mortality 67% Improvement Relative Risk N-acetylcysteine  Atefi et al.  LATE TREATMENT  RCT Is late treatment with N-acetylcysteine beneficial for COVID-19? RCT 60 patients in Iran Trial underpowered to detect differences Atefi et al., Immunity, Inflammation a.., Nov 2023 Favors N-acetylcysteine Favors control

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

Atefi et al., Immunity, Inflammation and Disease, doi:10.1002/iid3.1083, IRCT20200623047897N1
Nov 2023  
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14th 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.
3,800+ studies for 60+ treatments.
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.
risk of death, 66.7% lower, RR 0.33, p = 0.61, treatment 1 of 30 (3.3%), control 3 of 30 (10.0%), NNT 15.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Atefi et al., 20 Nov 2023, Single Blind Randomized Controlled Trial, Iran, peer-reviewed, 10 authors, trial IRCT20200623047897N1. Contact:,
This PaperN-acetylcys..All
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
Najmolsadat Atefi, Azadeh Goodarzi, Taghi Riahi, Niloofar Khodabandehloo, Mahshid Talebi Taher, Niloufar Najar Nobari, Farnoosh Seirafianpour, Zeinab Mahdi, Amir Baghestani, Rohollah Valizadeh
Immunity, Inflammation and Disease, doi:10.1002/iid3.1083
Background: The current absence of gold-standard or all-aspect favorable therapies for COVID-19 renders a focus on multipotential drugs proposed to prevent or treat this infection or ameliorate its signs and symptoms vitally important. The present well-designed randomized controlled trial (RCT) sought to evaluate the efficacy and safety of N-acetylcysteine (NAC) as adjuvant therapy for 60 hospitalized Iranian patients with COVID-19. Methods: Two 30-person diets, comprising 15 single diets of Kaletra (lopinavir/ritonavir) + hydroxychloroquine (HCQ) with/without NAC (600 mg TDS) and atazanavir/ritonavir + HCQ with/without NAC (600 mg TDS), were administered in the study. Results: At the end of the study, a further decrease in C-reactive protein was observed in the NAC group (P = 0.008), and no death occurred in the atazanavir/ritonavir + HCQ + NAC group, showing that the combination of these drugs may reduce mortality. The atazanavir/ritonavir + HCQ and atazanavir/ritonavir + NAC groups exhibited the highest O 2 saturation at the end of the study and a significant rise in O 2 saturation following intervention commencement, including NAC (P > 0.05). Accordingly, oral or intravenous NAC, if indicated, may enhance O 2 saturation, blunt the inflammation trend (by reducing C-reactive protein), and lower mortality in hospitalized patients with COVID-19.
AUTHOR CONTRIBUTIONS Azadeh Goodarzi and Najmolsadat Atefi conceived and planned the intervention. Taghi Riahi, Niloofar Khodabandehloo, Mahshid Talebi Taher and Niloufar Najar Nobari carried out the intervention. Zeinab Mahdi and Amir Baghestani gathering the datas. Amir Baghestani, Zeinab Mahdi, Rohollah Valizadeh, and Farnoosh Seirafianpour contributed to the interpretation of the results. Rohollah Valizadeh analyzed the data. Farnoosh Seirafianpour took the lead in writing the manuscript. All authors contributed to the preparation of data and the finalization of this article. All the figures have been produced by the authors of this article and are personal data. CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest.
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Late treatment
is less effective
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