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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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Mortality 85% Improvement Relative Risk Azithromycin  Atefi et al.  LATE TREATMENT Is late treatment with azithromycin beneficial for COVID-19? Retrospective 60 patients in Iran Lower mortality with azithromycin (not stat. sig., p=0.31) c19early.org Atefi et al., Immunity, Inflammation a.., Nov 2023 Favorsazithromycin Favorscontrol 0 0.5 1 1.5 2+
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. There was lower mortality for patients that received azithromycin, without statistical significance.
risk of death, 85.1% lower, RR 0.15, p = 0.31, treatment 0 of 18 (0.0%), control 4 of 42 (9.5%), NNT 10, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Atefi et al., 20 Nov 2023, retrospective, Iran, peer-reviewed, 10 authors, trial IRCT20200623047897N1. Contact: goodarzi.a@iums.ac.ir, azadeh_goodarzi1984@yahoo.com.
This PaperAzithromycinAll
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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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>At the end of the ' 'study, a further decrease in C‐reactive protein was observed in the NAC group ' '(<jats:italic>P</jats:italic>\u2009=\u20090.008), 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<jats:sub>2</jats:sub> saturation at the end of the study and a ' 'significant rise in O<jats:sub>2</jats:sub> saturation following intervention commencement, ' 'including NAC (<jats:italic>P</jats:italic>\u2009&gt;\u20090.05). Accordingly, oral or ' 'intravenous NAC, if indicated, may enhance O<jats:sub>2</jats:sub> saturation, blunt the ' 'inflammation trend (by reducing C‐reactive protein), and lower mortality in hospitalized ' 'patients with ' 'COVID‐19.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The NAC ' 'could be more effective as prophylactic or adjuvant therapy in stable non‐severe cases of ' 'COVID‐19 with a particularly positive role in the augmentation of O<jats:sub>2</jats:sub> ' 'saturation and faster reduction of the CRP level and inflammation or could be effective for ' 'better controlling of COVID‐19 or its therapy‐related side effects.</jats:p></jats:sec>', 'DOI': '10.1002/iid3.1083', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 11, 21]], 'date-time': '2023-11-21T21:42:09Z', 'timestamp': 1700602929000}, 'update-policy': 'http://dx.doi.org/10.1002/crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Evaluation of the efficacy and safety of oral <i>N</i>‐acetylcysteine in patients with COVID‐19 ' 'receiving the routine antiviral and hydroxychloroquine protocol: A randomized controlled ' 'clinical trial', 'prefix': '10.1002', 'volume': '11', 'author': [ { 'ORCID': 'http://orcid.org/0000-0003-1053-2441', 'authenticated-orcid': False, 'given': 'Najmolsadat', 'family': 'Atefi', 'sequence': 'first', 'affiliation': [ { 'name': 'Department of Dermatology, Rasool Akram Medical Complex Clinical ' 'Research Development Center (RCRDC), School of Medicine Iran ' 'University of Medical Sciences Tehran Iran'}]}, { 'ORCID': 'http://orcid.org/0000-0002-1249-4429', 'authenticated-orcid': False, 'given': 'Azadeh', 'family': 'Goodarzi', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Dermatology, Rasool Akram Medical Complex Clinical ' 'Research Development Center (RCRDC), School of Medicine Iran ' 'University of Medical Sciences Tehran Iran'}]}, { 'ORCID': 'http://orcid.org/0000-0001-7381-0790', 'authenticated-orcid': False, 'given': 'Taghi', 'family': 'Riahi', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Internal Medicine, School of Medicine Iran ' 'University of Medical Sciences Tehran Iran'}]}, { 'ORCID': 'http://orcid.org/0000-0002-0307-6014', 'authenticated-orcid': False, 'given': 'Niloofar', 'family': 'Khodabandehloo', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Geriatric Medicine, School of Medicine Iran ' 'University of Medical Sciences Tehran Iran'}]}, { 'ORCID': 'http://orcid.org/0000-0002-3133-7859', 'authenticated-orcid': False, 'given': 'Mahshid', 'family': 'Talebi Taher', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Infectious Disease, School of Medicine, ' 'Antimicrobial Resistance Research Center, Immunology and ' 'Infectious Disease Research Institute Iran University of Medical ' 'Sciences Tehran Iran'}]}, { 'ORCID': 'http://orcid.org/0000-0002-4245-1980', 'authenticated-orcid': False, 'given': 'Niloufar', 'family': 'Najar Nobari', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Dermatology, Rasool Akram Medical Complex Clinical ' 'Research Development Center (RCRDC), School of Medicine Iran ' 'University of Medical Sciences Tehran Iran'}]}, { 'ORCID': 'http://orcid.org/0000-0003-3794-6206', 'authenticated-orcid': False, 'given': 'Farnoosh', 'family': 'Seirafianpour', 'sequence': 'additional', 'affiliation': [ { 'name': 'Razi Drug Research Center Iran University of Medical Sciences ' 'Tehran Iran'}]}, { 'ORCID': 'http://orcid.org/0000-0003-1114-8660', 'authenticated-orcid': False, 'given': 'Zeinab', 'family': 'Mahdi', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Dermatology, Rasool Akram Medical Complex Clinical ' 'Research Development Center (RCRDC), School of Medicine Iran ' 'University of Medical Sciences Tehran Iran'}]}, { 'given': 'Amir', 'family': 'Baghestani', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of General Medicine, Rasool Akram Medical Complex, ' 'School of Medicine Iran University of Medical Sciences Tehran ' 'Iran'}]}, { 'ORCID': 'http://orcid.org/0000-0002-6913-3210', 'authenticated-orcid': False, 'given': 'Rohollah', 'family': 'Valizadeh', 'sequence': 'additional', 'affiliation': [{'name': 'Urmia University of Medical Sciences Urmia Iran'}]}], 'member': '311', 'published-online': {'date-parts': [[2023, 11, 20]]}, 'reference': [ { 'key': 'e_1_2_10_2_1', 'first-page': '959', 'article-title': 'N‐acetylcysteine as a potential treatment for COVID‐19', 'volume': '15', 'author': 'Jorge‐Aarón R‐M', 'year': '2020', 'journal-title': 'Future Med'}, { 'issue': '10223', 'key': 'e_1_2_10_3_1', 'doi-asserted-by': 'crossref', 'first-page': '514', 'DOI': '10.1016/S0140-6736(20)30154-9', 'article-title': 'A familial cluster of pneumonia associated with the 2019 novel ' 'coronavirus indicating person‐to‐person transmission: a study of a ' 'family cluster', 'volume': '395', 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'2021', 'journal-title': 'Clin Toxicol'}, { 'key': 'e_1_2_10_48_1', 'doi-asserted-by': 'crossref', 'first-page': '1584', 'DOI': '10.2174/18734316MTEyyNzY6y', 'article-title': 'The potential mechanism of N‐acetylcysteine in treating COVID‐19', 'volume': '2', 'author': 'Zhou N', 'year': '2021', 'journal-title': 'Curr Pharm Biotechnol'}, { 'issue': '6', 'key': 'e_1_2_10_49_1', 'first-page': '2802', 'article-title': 'Therapeutic potential of N‐acetyl cysteine (NAC) in preventing cytokine ' 'storm in COVID‐19: review of current evidence', 'volume': '25', 'author': 'Mohanty RR', 'year': '2021', 'journal-title': 'Eur Rev Med Pharmacol Sci'}, { 'issue': '14', 'key': 'e_1_2_10_50_1', 'doi-asserted-by': 'crossref', 'first-page': '1207', 'DOI': '10.1089/ars.2020.8247', 'article-title': 'N‐acetylcysteine and hydrogen sulfide in coronavirus disease 2019', 'volume': '35', 'author': 'Bourgonje AR', 'year': '2021', 'journal-title': 'Antioxid Redox Signal'}, { 'issue': '12', 'key': 'e_1_2_10_51_1', 'doi-asserted-by': 'crossref', 'DOI': '10.1111/ijcp.14720', 'article-title': 'Severe and life‐threatening COVID‐19‐related mucocutaneous eruptions: a ' 'systematic review', 'volume': '75', 'author': 'Mashayekhi F', 'year': '2021', 'journal-title': 'Int J Clin Pract'}, { 'key': 'e_1_2_10_52_1', 'article-title': 'Efficacy of glutathione therapy in relieving dyspnea associated with ' 'COVID‐19 pneumonia: a report of 2 cases', 'volume': '30', 'author': 'Horowitz RI', 'year': '2020', 'journal-title': 'Respir Med Case Rep'}, { 'key': 'e_1_2_10_53_1', 'first-page': '123', 'article-title': 'Geriatric challenges in the new coronavirus disease‐19 (COVID‐19) ' 'pandemic: a systematic review', 'volume': '34', 'author': 'Mohamadi M', 'year': '2020', 'journal-title': 'Med J Islam Repub Iran'}, { 'issue': '4', 'key': 'e_1_2_10_54_1', 'doi-asserted-by': 'crossref', 'DOI': '10.1111/dth.13733', 'article-title': 'Treatment of COVID‐19 with pentoxifylline: could it be a potential ' 'adjuvant therapy?', 'volume': '33', 'author': 'Seirafianpour F', 'year': '2020', 'journal-title': 'Dermatol Ther'}, { 'issue': '2', 'key': 'e_1_2_10_55_1', 'doi-asserted-by': 'crossref', 'DOI': '10.34172/ipp.2021.36', 'article-title': 'Accuracy of chest computed tomography and reverse transcription ' 'polymerase chain reaction in diagnosis of 2019 novel coronavirus ' 'disease; a systematic review and meta‐analysis', 'volume': '7', 'author': 'Shokraee K', 'year': '2021', 'journal-title': 'Immunopathol Persa'}, { 'issue': '1', 'key': 'e_1_2_10_56_1', 'first-page': '9', 'article-title': 'Systemic retinoids in the COVID‐19 era–are they helpful, safe, or ' 'harmful? A comprehensive systematized review', 'volume': '23', 'author': 'Sadeghzadeh‐Bazargan A', 'year': '2020', 'journal-title': 'Iran J Dermatol'}, { 'issue': '1', 'key': 'e_1_2_10_57_1', 'first-page': '13', 'article-title': 'Cytokine storm and probable role of immunoregulatory drugs in COVID‐19: ' 'a comprehensive review', 'volume': '23', 'author': 'Sadeghzadeh‐Bazargan A', 'year': '2020', 'journal-title': 'Iranian J Dermatol'}, { 'key': 'e_1_2_10_58_1', 'first-page': '4', 'article-title': 'A comprehensive review on COVID‐19 infection and comorbidities of ' 'various organs', 'author': 'Goodarzi A', 'year': '2021', 'journal-title': 'Acta Med Iranica'}, { 'issue': '1', 'key': 'e_1_2_10_59_1', 'first-page': '865', 'article-title': 'The effect of influenza vaccine on severity of COVID‐19 infection: an ' 'original study from Iran', 'volume': '35', 'author': 'Kalantari S', 'year': '2021', 'journal-title': 'Med J Islam Repub Iran'}, { 'issue': '1', 'key': 'e_1_2_10_60_1', 'first-page': '481', 'article-title': 'Histopathologic survey on lung necropsy specimens of 15 patients who ' 'died from COVID‐19: a large study from Iran with a high rate of ' 'anthracosis', 'volume': '35', 'author': 'Kooranifar S', 'year': '2021', 'journal-title': 'Med J Islam Repub Iran'}, { 'key': 'e_1_2_10_61_1', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.bios.2020.112752', 'article-title': 'COVID‐19 diagnosis—a review of current methods', 'volume': '172', 'author': 'Yüce M', 'year': '2021', 'journal-title': 'Biosens Bioelectron'}, { 'issue': '1', 'key': 'e_1_2_10_62_1', 'first-page': '81', 'article-title': 'Histopathologic changes and cellular events of organs systems in ' 'COVID‐19', 'volume': '6', 'author': 'Nobari NN', 'year': '2021', 'journal-title': 'J Cell Mol Anesth'}, { 'issue': '5', 'key': 'e_1_2_10_63_1', 'article-title': 'Obesity as an independent risk factor for COVID‐19 severity and ' 'mortality', 'volume': '5', 'author': 'Tadayon Najafabadi B', 'year': '2023', 'journal-title': 'Cochrane Database Syst Rev'}, { 'issue': '1', 'key': 'e_1_2_10_64_1', 'first-page': '870', 'article-title': 'The effect of opium on severity of COVID‐19 infection: an original ' 'study from Iran', 'volume': '35', 'author': 'Riahi T', 'year': '2021', 'journal-title': 'Med J Islam Repub Iran'}], 'container-title': 'Immunity, Inflammation and Disease', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://onlinelibrary.wiley.com/doi/pdf/10.1002/iid3.1083', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 11, 21]], 'date-time': '2023-11-21T21:42:42Z', 'timestamp': 1700602962000}, 'score': 1, 'resource': {'primary': {'URL': 'https://onlinelibrary.wiley.com/doi/10.1002/iid3.1083'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 11]]}, 'references-count': 63, 'journal-issue': {'issue': '11', 'published-print': {'date-parts': [[2023, 11]]}}, 'alternative-id': ['10.1002/iid3.1083'], 'URL': 'http://dx.doi.org/10.1002/iid3.1083', 'relation': {}, 'ISSN': ['2050-4527', '2050-4527'], 'subject': ['Immunology', 'Immunology and Allergy'], 'container-title-short': 'Immunity Inflam &amp;amp; Disease', 'published': {'date-parts': [[2023, 11]]}, 'assertion': [ { 'value': '2023-06-13', 'order': 0, 'name': 'received', 'label': 'Received', 'group': {'name': 'publication_history', 'label': 'Publication History'}}, { 'value': '2023-10-31', 'order': 1, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'publication_history', 'label': 'Publication History'}}, { 'value': '2023-11-20', 'order': 2, 'name': 'published', 'label': 'Published', 'group': {'name': 'publication_history', 'label': 'Publication History'}}]}
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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