Evaluation of the recovery rate and prevention of hospitalization among covid-19 outpatients: a randomized clinical trial comparing N-acetylcysteine with Bromhexine

DOI record: { "DOI": "10.21203/rs.3.rs-2309373/v2", "URL": "http://dx.doi.org/10.21203/rs.3.rs-2309373/v2", "abstract": "<jats:title>Abstract</jats:title>\n <jats:p>Objectives: Due to the referral of COVID-19 patients to outpatient centers in the early stages, the aim of the present study is to compare the effect of N-acetylcysteine and Bromhexine on the recovery rate and prevention of hospitalization in outpatients with COVID-19\nMethodology: This study was conducted from April 2022 to September 2022. First, PCR-confirmed COVID-19 patients were divided into tree groups, one of these groups received N-acetylcysteine while the other received bromhexine and One of these groups did not receive any medication. The patients were followed up on the seventh and fourteenth days of the disease in terms of the duration of changes in oxygen saturation and recovery. The hospitalization and death of the patients were also evaluated after one month.\nResults: Out of 225 studied patients, oxygen saturation was increased by 1.33% in the third visit of the patients who received N-acetylcysteine compared to their first visit. This percentage was 1.19% in the patients who received bromhexine.29.77% of the patients were admitted to the hospital and 70.23% of them had no history of hospitalization within 14 day and their mortality rate was 9.33% in control group and it was zero in both groups of patients who received drug.\nConclusions: The results of this study showed that early initiation of Bromhexine and N-acetylcysteine can effectively reduce the hospitalization rate and mortality and shorten the duration of hospitalization.\nClinical trial code: IRCT20220302054167N1 and ethics code: IR.UMSHA.REC.1400.957</jats:p>", "accepted": { "date-parts": [ [ 2022, 11, 24 ] ] }, "author": [ { "affiliation": [ { "name": "Hamedan University of medical science" } ], "family": "Ghayour", "given": "Anahita Eslami", "sequence": "first" }, { "affiliation": [ { "name": "Hamedan University of medical science" } ], "family": "Nazari", "given": "Sasan", "sequence": "additional" }, { "affiliation": [ { "name": "Hamedan University of medical science" } ], "family": "Keramat", "given": "Fariba", "sequence": "additional" }, { "affiliation": [ { "name": "Hamedan University of medical science" } ], "family": "Shahbazi", "given": "Fatemeh", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2023, 4, 3 ] ], "date-time": "2023-04-03T19:54:07Z", "timestamp": 1680551647000 }, "deposited": { "date-parts": [ [ 2023, 5, 23 ] ], "date-time": "2023-05-23T18:44:17Z", "timestamp": 1684867457000 }, "group-title": "In Review", "indexed": { "date-parts": [ [ 2024, 3, 3 ] ], "date-time": "2024-03-03T12:57:56Z", "timestamp": 1709470676470 }, "institution": [ { "name": "Research Square" } ], "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2023, 4, 3 ] ] }, "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "unspecified", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 4, 3 ] ], "date-time": "2023-04-03T00:00:00Z", "timestamp": 1680480000000 } } ], "link": [ { "URL": "https://www.researchsquare.com/article/rs-2309373/v2", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.researchsquare.com/article/rs-2309373/v2.html", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "8761", "original-title": [], "posted": { "date-parts": [ [ 2023, 4, 3 ] ] }, "prefix": "10.21203", "published": { "date-parts": [ [ 2023, 4, 3 ] ] }, "publisher": "Research Square Platform LLC", "reference": [ { "DOI": "10.1038/s41564-020-0709-x", "article-title": "The new scope of virus taxonomy: partitioning the virosphere into 15 hierarchical ranks", "author": "International Committee on Taxonomy of Viruses Executive Committee", "doi-asserted-by": "publisher", "first-page": "668", "issue": "5", "journal-title": "Nat Microbiol", "key": "ref1", "unstructured": "International Committee on Taxonomy of Viruses Executive Committee. The new scope of virus taxonomy: partitioning the virosphere into 15 hierarchical ranks. Nat Microbiol. 2020;5(5):668–74. doi:10.1038/s41564-020-0709-x.", "volume": "5", "year": "2020" }, { "DOI": "10.2147/TCRM.S273700", "article-title": "N-Acetylcysteine to Combat COVID-19: An Evidence Review", "author": "Shi Z", "doi-asserted-by": "publisher", "first-page": "1047", "journal-title": "Ther Clin Risk Manag", "key": "ref2", "unstructured": "Shi Z, Puyo CA. N-Acetylcysteine to Combat COVID-19: An Evidence Review. Ther Clin Risk Manag. 2020;16:1047–55. doi:10.2147/TCRM.S273700. Published 2020 Nov 2.", "volume": "16", "year": "2020" }, { "DOI": "10.21037/qims-20-564", "article-title": "A systematic review of chest imaging findings in COVID-19", "author": "Sun Z", "doi-asserted-by": "publisher", "first-page": "1058", "issue": "5", "journal-title": "Quant Imaging Med Surg", "key": "ref3", "unstructured": "Sun Z, Zhang N, Li Y, Xu X. A systematic review of chest imaging findings in COVID-19. Quant Imaging Med Surg. 2020;10(5):1058–79. doi:10.21037/qims-20-564.", "volume": "10", "year": "2020" }, { "DOI": "10.1002/jmv.20255", "article-title": "An interferon-gamma-related cytokine storm in SARS patients", "author": "Huang KJ", "doi-asserted-by": "publisher", "first-page": "185", "issue": "2", "journal-title": "J Med Virol", "key": "ref4", "unstructured": "Huang KJ, Su IJ, Theron M, et al. An interferon-gamma-related cytokine storm in SARS patients. J Med Virol. 2005;75(2):185–94. doi:10.1002/jmv.20255.", "volume": "75", "year": "2005" }, { "DOI": "10.3390/v11020168", "article-title": "Myeloid Cells during Viral Infections and Inflammation", "author": "Stegelmeier AA", "doi-asserted-by": "publisher", "first-page": "168", "issue": "2", "journal-title": "Viruses", "key": "ref5", "unstructured": "Stegelmeier AA, van Vloten JP, Mould RC, et al. Myeloid Cells during Viral Infections and Inflammation. Viruses. 2019;11(2):168. doi:10.3390/v11020168. Published 2019 Feb 19.", "volume": "11", "year": "2019" }, { "DOI": "10.1016/j.cell.2020.08.001", "article-title": "Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment", "author": "Schulte-Schrepping J", "doi-asserted-by": "publisher", "first-page": "1419", "issue": "6", "journal-title": "Cell", "key": "ref6", "unstructured": "Schulte-Schrepping J, Reusch N, Paclik D, et al. Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment. Cell. 2020;182(6):1419–40.e23. doi:10.1016/j.cell.2020.08.001.", "volume": "182", "year": "2020" }, { "DOI": "10.1016/j.pcad.2020.02.007", "article-title": "Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus", "author": "McCarty MF", "doi-asserted-by": "publisher", "first-page": "383", "issue": "3", "journal-title": "Prog Cardiovasc Dis", "key": "ref7", "unstructured": "McCarty MF, DiNicolantonio JJ. Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus. Prog Cardiovasc Dis. 2020;63(3):383–5. doi:10.1016/j.pcad.2020.02.007.", "volume": "63", "year": "2020" }, { "DOI": "10.1016/j.niox.2020.06.002", "article-title": "Tackle the free radicals damage in COVID-19", "author": "Wu J", "doi-asserted-by": "publisher", "first-page": "39", "journal-title": "Nitric Oxide", "key": "ref8", "unstructured": "Wu J. Tackle the free radicals damage in COVID-19. Nitric Oxide. 2020;102:39–41. doi:10.1016/j.niox.2020.06.002.", "volume": "102", "year": "2020" }, { "DOI": "10.1371/journal.ppat.1006286", "article-title": "The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells", "author": "Poppe M", "doi-asserted-by": "publisher", "first-page": "e1006286", "issue": "3", "journal-title": "PLoS Pathog", "key": "ref9", "unstructured": "Poppe M, Wittig S, Jurida L, et al. The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells. PLoS Pathog. 2017;13(3):e1006286. doi:10.1371/journal.ppat.1006286. Published 2017 Mar 29.", "volume": "13", "year": "2017" }, { "DOI": "10.3109/15563650.2012.659252", "author": "Rumack BH", "doi-asserted-by": "publisher", "key": "ref10", "unstructured": "Rumack BH, Bateman DN. Acetaminophen and acetylcysteine dose and duration: past, present and future [published correction appears in Clin Toxicol (Phila). 2021 Apr;59(4):359] [published correction appears in Clin Toxicol (Phila). 2021 Dec;59(12):1195]. ClinToxicol(Phila).2012; 50(2):91–98. doi:10.3109/15563650.2012.659252.", "year": "2021" }, { "DOI": "10.3904/kjim.2019.105", "article-title": "N-acetylcysteine decreases airway inflammation and responsiveness in asthma by modulating claudin 18 expression", "author": "Lee PH", "doi-asserted-by": "publisher", "first-page": "1229", "issue": "5", "journal-title": "Korean J Intern Med", "key": "ref11", "unstructured": "Lee PH, Hong J, Jang AS. N-acetylcysteine decreases airway inflammation and responsiveness in asthma by modulating claudin 18 expression. Korean J Intern Med. 2020;35(5):1229–37. doi:10.3904/kjim.2019.105.", "volume": "35", "year": "2020" }, { "DOI": "10.3390/antiox8050111", "author": "Šalamon Š", "doi-asserted-by": "publisher", "key": "ref12", "unstructured": "Šalamon Š, Kramar B, Marolt TP, Poljšak B, Milisav I. Medical and Dietary Uses of N-Acetylcysteine. Antioxidants (Basel). 2019;8(5):111. Published 2019 Apr 28. doi:10.3390/antiox8050111.", "year": "2019" }, { "article-title": "Use of N-acetylcysteine in the management of coronary artery diseases", "author": "Marchetti G", "first-page": "633", "issue": "7", "journal-title": "Cardiologia", "key": "ref13", "unstructured": "Marchetti G, Lodola E, Licciardello L, Colombo A. Use of N-acetylcysteine in the management of coronary artery diseases. Cardiologia. 1999;44(7):633–7.", "volume": "44", "year": "1999" }, { "DOI": "10.1378/chest.105.1.190", "article-title": "N-acetylcysteine enhances recovery from acute lung injury in man. A randomized, double-blind, placebo-controlled clinical study", "author": "Suter PM", "doi-asserted-by": "publisher", "first-page": "190", "issue": "1", "journal-title": "Chest", "key": "ref14", "unstructured": "Suter PM, Domenighetti G, Schaller MD, Laverrière MC, Ritz R, Perret C. N-acetylcysteine enhances recovery from acute lung injury in man. A randomized, double-blind, placebo-controlled clinical study. Chest. 1994;105(1):190–4. doi:10.1378/chest.105.1.190.", "volume": "105", "year": "1994" }, { "DOI": "10.1186/s12879-022-07312-7", "article-title": "Demographics, clinical characteristics, and outcomes of 27,256 hospitalized COVID-19 patients in Kermanshah Province, Iran: a retrospective one-year cohort study", "author": "Hesni E", "doi-asserted-by": "publisher", "first-page": "319", "journal-title": "BMC Infect Dis", "key": "ref15", "unstructured": "Hesni E, Sayad B, Shadmani K. F. et al. Demographics, clinical characteristics, and outcomes of 27,256 hospitalized COVID-19 patients in Kermanshah Province, Iran: a retrospective one-year cohort study. BMC Infect Dis. 2022;22:319. doi.org/10.1186/s12879-022-07312-7.", "volume": "22", "year": "2022" }, { "DOI": "10.1177/00368504221074574", "article-title": "Use of N-Acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19", "author": "Izquierdo JL", "doi-asserted-by": "publisher", "first-page": "368504221074574", "issue": "1", "journal-title": "Sci Prog", "key": "ref16", "unstructured": "Izquierdo JL, Soriano JB, González Y, et al. Use of N-Acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19. Sci Prog. 2022;105(1):368504221074574. doi:10.1177/00368504221074574.", "volume": "105", "year": "2022" }, { "DOI": "10.34172/bi.2020.27", "article-title": "Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial", "author": "Ansarin K", "doi-asserted-by": "publisher", "first-page": "209", "issue": "4", "journal-title": "Bioimpacts", "key": "ref17", "unstructured": "Ansarin K, Tolouian R, Ardalan M, et al. Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial. Bioimpacts. 2020;10(4):209–15. doi:10.34172/bi.2020.27.", "volume": "10", "year": "2020" }, { "key": "ref18", "unstructured": "JohnsHopkins Coronavirus Resource Center (CRC). (2022) Https://coronavirus.jhu.edu/data/mortality." }, { "DOI": "10.1007/s43440-021-00296-2", "article-title": "A pilot study on intravenous N-Acetylcysteine treatment in patients with mild-to-moderate COVID19-associated acute respiratory distress syndrome", "author": "Taher A", "doi-asserted-by": "publisher", "first-page": "1650", "issue": "6", "journal-title": "Pharmacol Rep", "key": "ref19", "unstructured": "Taher A, Lashgari M, Sedighi L, Rahimi-Bashar F, Poorolajal J, Mehrpooya M. A pilot study on intravenous N-Acetylcysteine treatment in patients with mild-to-moderate COVID19-associated acute respiratory distress syndrome. Pharmacol Rep. 2021 Dec;73(6):1650–9. doi:10.1007/s43440-021-00296-2. Epub 2021 Jun 10. PMID: 34114174; PMCID: PMC8191712.", "volume": "73", "year": "2021" } ], "reference-count": 19, "references-count": 19, "relation": { "has-version": [ { "asserted-by": "object", "id": "10.21203/rs.3.rs-2309373/v3", "id-type": "doi" }, { "asserted-by": "object", "id": "10.21203/rs.3.rs-2309373/v1", "id-type": "doi" }, { "asserted-by": "object", "id": "10.21203/rs.3.rs-2309373/v4", "id-type": "doi" } ], "is-version-of": [ { "asserted-by": "subject", "id": "10.21203/rs.3.rs-2309373/v1", "id-type": "doi" }, { "asserted-by": "subject", "id": "10.21203/rs.3.rs-2309373/v3", "id-type": "doi" }, { "asserted-by": "subject", "id": "10.21203/rs.3.rs-2309373/v4", "id-type": "doi" } ] }, "resource": { "primary": { "URL": "https://www.researchsquare.com/article/rs-2309373/v2" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "subtype": "preprint", "title": "Evaluation of the recovery rate and prevention of hospitalization among covid-19 outpatients: a randomized clinical trial comparing N-acetylcysteine with Bromhexine", "type": "posted-content" }