{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:16:57Z","timestamp":1786720617502,"version":"build-2736575974"},"reference-count":88,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>SARS-CoV-2 infection leads to a heterogenous spectrum of clinical conditions ranging from self-limiting upper airway infection to severe respiratory failure. Carbocysteine is a thioether mucolytic with antioxidant and anti-inflammatory activities. Carbocysteine has been shown to have anti-viral effects on human rhinovirus, RSV and the influenza virus as well as interfering with upper airway ciliary motility, the first site of SARS-CoV-2 infection, leading to more effective mucus clearance and potential containment of viral spread towards the lower airway. Positive effects, in terms of limiting superimposed bacterial infection and reducing oxidative stress, have also been documented in COPD patients. Accordingly, Carbocysteine should also be considered in both post-exposure prophylaxis and early-phase treatment of COVID-19 in combination with other agents (monoclonal antibodies, antivirals, non-steroidal anti-inflammatory agents, and inhaled corticosteroids). In this review, we explored the pharmacokinetic and pharmacodynamic aspects of Carbocysteine to delineate its potential therapeutic impact in patients with COVID-19.<\/jats:p>","DOI":"10.3390\/life12111824","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T02:44:32Z","timestamp":1667961872000},"page":"1824","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mucolytic and Antioxidant Properties of Carbocysteine as a Strategy in COVID-19 Therapy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4692-5901","authenticated-orcid":false,"given":"Andrea","family":"Bianco","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cL. Vanvitelli\u201d, 80131 Naples, Italy"},{"name":"U.O.C. Clinica Pneumologica \u201cL. Vanvitelli\u201d, A.O. dei Colli, Ospedale Monaldi, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Conte","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cL. Vanvitelli\u201d, 80131 Naples, Italy"},{"name":"U.O.C. Clinica Pneumologica \u201cL. Vanvitelli\u201d, A.O. dei Colli, Ospedale Monaldi, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"Mariniello","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cL. Vanvitelli\u201d, 80131 Naples, Italy"},{"name":"U.O.C. Clinica Pneumologica \u201cL. Vanvitelli\u201d, A.O. dei Colli, Ospedale Monaldi, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3288-2808","authenticated-orcid":false,"given":"Valentino","family":"Allocca","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cL. Vanvitelli\u201d, 80131 Naples, Italy"},{"name":"U.O.C. Clinica Pneumologica \u201cL. Vanvitelli\u201d, A.O. dei Colli, Ospedale Monaldi, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Matera","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology, Department of Experimental Medicine, University of Campania \u201cL. Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"D\u2019Agnano","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cL. Vanvitelli\u201d, 80131 Naples, Italy"},{"name":"U.O.C. Clinica Pneumologica \u201cL. Vanvitelli\u201d, A.O. dei Colli, Ospedale Monaldi, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Lanata","sequence":"additional","affiliation":[{"name":"Medical Department, Domp\u00e9 Farmaceutici SpA, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4895-9707","authenticated-orcid":false,"given":"Mario","family":"Cazzola","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-7037","authenticated-orcid":false,"given":"Fabio","family":"Perrotta","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cL. Vanvitelli\u201d, 80131 Naples, Italy"},{"name":"U.O.C. Clinica Pneumologica \u201cL. Vanvitelli\u201d, A.O. dei Colli, Ospedale Monaldi, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Perrotta, F., Matera, M.G., Cazzola, M., and Bianco, A. (2020). Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter?. Respir. Med., 168.","DOI":"10.1016\/j.rmed.2020.105996"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s00408-020-00408-4","article-title":"ACE2: The Major Cell Entry Receptor for SARS-CoV-2","volume":"198","author":"Scialo","year":"2020","journal-title":"Lung"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tang, Y., Liu, J., Zhang, D., Xu, Z., Ji, J., and Wen, C. (2020). Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01708"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1007\/s11239-020-02242-0","article-title":"Anticoagulant treatment in COVID-19: A narrative review","volume":"51","author":"Carfora","year":"2021","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_5","first-page":"272","article-title":"COVID-19 and coagulative axis: Review of emerging aspects in a novel disease","volume":"19","author":"Boccia","year":"2020","journal-title":"Monaldi Arch. Chest Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Jamwal, S., Gautam, A., Elsworth, J., Kumar, M., Chawla, R., and Kumar, P. (2020). An updated insight into the molecular pathogenesis, secondary complications and potential therapeutics of COVID-19 pandemic. Life Sci., 257.","DOI":"10.1016\/j.lfs.2020.118105"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S2213-2600(20)30079-5","article-title":"Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study","volume":"8","author":"Yang","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1097\/CM9.0000000000000824","article-title":"Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: A retrospective study","volume":"133","author":"Deng","year":"2020","journal-title":"Chin. Med. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.4049\/jimmunol.2000413","article-title":"COVID-19 as an Acute Inflammatory Disease","volume":"205","author":"Manjili","year":"2020","journal-title":"J. Immunol."},{"key":"ref_10","first-page":"12","article-title":"COVID-19 infection and oxidative stress: An under-explored approach for prevention and treatment?","volume":"35","year":"2020","journal-title":"Pan. Afr. Med. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9200","DOI":"10.1074\/jbc.M512529200","article-title":"Significant redox insensitivity of the functions of the SARS-CoV spike glycoprotein: Comparison with HIV envelope","volume":"281","author":"Lavillette","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Abdi, A., Jalilian, M., Sarbarzeh, P.A., and Vlaisavljevic, Z. (2020). Diabetes and COVID-19: A systematic review on the current evidences. Diabetes Res. Clin. Pract., 166.","DOI":"10.1016\/j.diabres.2020.108347"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1016\/S1470-2045(20)30442-3","article-title":"COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: A prospective cohort study","volume":"21","author":"Lee","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_14","first-page":"480","article-title":"Pharmacokinetic behavior of S-carboxymethylcysteine-Lys in patients with chronic bronchitis","volume":"4","author":"Braga","year":"1982","journal-title":"Clin. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"659","DOI":"10.2147\/COPD.S3735","article-title":"The role for S-carboxymethylcysteine (Carbocysteine) in the management of chronic obstructive pulmonary disease","volume":"3","author":"Hooper","year":"2008","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/S0140-6736(08)61682-7","article-title":"Carbocysteine for acute exacerbations of COPD","volume":"372","author":"Mohapatra","year":"2008","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1515\/DMDI.1988.6.3-4.253","article-title":"Pharmacogenetics of the S-Oxidation of S-Carboxymethyl-L-Cysteine","volume":"6","author":"Waring","year":"1988","journal-title":"Drug Metab. Drug Interactions"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.addr.2008.09.008","article-title":"Barrier properties of mucus","volume":"61","author":"Cone","year":"2009","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1378\/chest.130.4.1102","article-title":"Epithelial Mucin Stores Are Increased in the Large Airways of Smokers with Airflow Obstruction","volume":"130","author":"Innes","year":"2006","journal-title":"Chest"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1513\/pats.2306016","article-title":"From mucins to mucus: Toward a more coherent understanding of this essential barrier","volume":"1","author":"Thornton","year":"2004","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.addr.2008.09.012","article-title":"Micro- and macrorheology of mucus","volume":"61","author":"Lai","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.otc.2009.11.002","article-title":"Mucus and mucins","volume":"43","author":"Rubin","year":"2010","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1152\/physrev.00004.2021","article-title":"Physiology and Pathophysiology of Human Airway Mucus","volume":"102","author":"Hill","year":"2022","journal-title":"Physiol. Rev."},{"key":"ref_24","first-page":"465","article-title":"Chemical markers of mucous and serum glycoproteins and their relation to viscosity in mucoid and purulent sputum from various hypersecretory diseases","volume":"117","author":"Reid","year":"1978","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_25","first-page":"81","article-title":"Biochemical mode of action of cysteine by-products on the bronchial mucus","volume":"26","author":"Havez","year":"1970","journal-title":"Le Poumon et le coeur"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1378\/chest.70.4.506","article-title":"S-Carboxymethylcysteine in the Fluidification of Sputum and Treatment of Chronic Airway Obstruction","volume":"70","author":"Edwards","year":"1976","journal-title":"Chest"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1159\/000195871","article-title":"Long-lasting effects on rheology and clearance of bronchial mucus after short-term administration of high doses of carbocysteine-lysine to patients with chronic bronchitis","volume":"57","author":"Braga","year":"1990","journal-title":"Respiration"},{"key":"ref_28","first-page":"331","article-title":"Comparison between penetration of amoxicillin combined with carbocysteine and amoxicillin alone in pathological bronchial secretions and pulmonary tissue","volume":"5","author":"Braga","year":"1985","journal-title":"Int. J. Clin. Pharmacol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1164\/rccm.200407-887OC","article-title":"Oxidative Stress and Respiratory Muscle Dysfunction in Severe Chronic Obstructive Pulmonary Disease","volume":"171","author":"Barreiro","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/aps.2015.150","article-title":"Carbocysteine attenuates TNF-\u03b1-induced inflammation in human alveolar epithelial cells in vitro through suppressing NF-\u03baB and ERK1\/2 MAPK signaling pathways","volume":"37","author":"Wang","year":"2016","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/j.1532-5415.2005.00592_9.x","article-title":"Carbocysteine Reduces Frequency of Common Colds and Exacerbations in Patients with Chronic Obstructive Pulmonary Disease","volume":"54","author":"Yasuda","year":"2006","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1111\/j.1532-5415.2007.01373.x","article-title":"CARBOCYSTEINE IMPROVES QUALITY OF LIFE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE","volume":"55","author":"Tatsumi","year":"2007","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1002\/jcp.25710","article-title":"Effects of Carbocysteine and Beclomethasone on Histone Acetylation\/Deacetylation Processes in Cigarette Smoke Exposed Bronchial Epithelial Cells","volume":"232","author":"Pace","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.toxlet.2013.09.013","article-title":"Carbocysteine regulates innate immune responses and senescence processes in cigarette smoke stimulated bronchial epithelial cells","volume":"223","author":"Pace","year":"2013","journal-title":"Toxicol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s12192-013-0424-0","article-title":"Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bron-chial epithelial cells","volume":"18","author":"Pace","year":"2013","journal-title":"Cell Stress Chaperon"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ejphar.2004.10.007","article-title":"Exhaled Interleukine-6 and 8-isoprostane in chronic obstructive pulmonary disease: Effect of carbocysteine lysine salt monohydrate (SCMC-Lys)","volume":"505","author":"Carpagnano","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Dos Santos, C.F., Braz, M.G., de Arruda, N.M., Caram, L., Nogueira, D.L., Tanni, S.E., de Godoy, I., and Ferrari, R. (2022). DNA damage and antioxidant capacity in COPD patients with and without lung cancer. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0275873"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.ccm.2007.06.008","article-title":"Pathogenesis of chronic obstructive pulmonary disease","volume":"28","author":"Macnee","year":"2007","journal-title":"Clin. Chest. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.resp.2009.04.016","article-title":"l-Carbocysteine reduces neutrophil elastase-induced mucin production","volume":"167","author":"Yasuo","year":"2009","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.2147\/COPD.S106160","article-title":"Acute exacerbation of COPD: Is it the \u201cstroke of the lungs\u201d?","volume":"11","author":"Hillas","year":"2016","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1513\/AnnalsATS.201710-815OC","article-title":"Myocardial Infarction and Ischemic Stroke after Exacerbations of Chronic Obstructive Pulmonary Disease","volume":"15","author":"Rothnie","year":"2018","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1136\/thoraxjnl-2011-201395","article-title":"Increased circulating endothelial microparticles in COPD patients: A potential biomarker for COPD exacerbation susceptibility","volume":"67","author":"Takahashi","year":"2012","journal-title":"Thorax"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1586\/17474086.2013.814835","article-title":"Platelet activation as a novel mechanism of atherothrombotic risk in chronic obstructive pulmonary disease","volume":"6","author":"Malerba","year":"2013","journal-title":"Expert Rev. Hematol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ambrosino, P., Bachetti, T., D\u2019Anna, S.E., Galloway, B., Bianco, A., D\u2019Agnano, V., Papa, A., Motta, A., Perrotta, F., and Maniscalco, M. (2022). Mechanisms and Clinical Implications of Endothelial Dysfunction in Arterial Hypertension. J. Cardiovasc. Dev. Dis., 9.","DOI":"10.3390\/jcdd9050136"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"11954","DOI":"10.1074\/jbc.M205329200","article-title":"Human Rhinovirus Selectively Modulates Membranous and Soluble Forms of Its Intercellular Adhesion Molecule\u20131 (ICAM-1) Receptor to Promote Epithelial Cell Infectivity","volume":"278","author":"Whiteman","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1046\/j.1365-2249.2000.01301.x","article-title":"Expression of intercellular adhesion molecule-1 (ICAM-1) in nasal epithelial cells of atopic subjects: A mechanism for increased rhinovirus infection?","volume":"121","author":"Bianco","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1046\/j.1365-2249.1997.4221440.x","article-title":"Interferon-gamma (IFN-\u03b3) down-regulates the rhinovirus-induced expression of intercellular adhesion molecule-1 (ICAM-1) on human airway epithelial cells","volume":"110","author":"Sethi","year":"1997","journal-title":"Clin. Exp. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1183\/09031936.98.12030619","article-title":"Th2 cytokines exert a dominant influence on epithelial cell expression of the major group human rhinovirus receptor, ICAM-1","volume":"12","author":"Bianco","year":"1998","journal-title":"Eur. Respir. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0882-4010(03)00048-2","article-title":"S-carboxymethylcysteine inhibits the attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells","volume":"34","author":"Cakan","year":"2003","journal-title":"Microb. Pathog."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1183\/09031936.94.07091673","article-title":"Circulating cell adhesion molecules in bronchial lavage and serum in COPD patients with chronic bronchitis","volume":"7","author":"Riise","year":"1994","journal-title":"Eur. Respir. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.4103\/0366-6999.162494","article-title":"Epithelial Sodium and Chloride Channels and Asthma","volume":"128","author":"Wang","year":"2015","journal-title":"Chin. Med J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s12931-016-0437-1","article-title":"A HuR\/TGF-\u03b21 feedback circuit regulates airway remodeling in airway smooth muscle cells","volume":"17","author":"Wang","year":"2016","journal-title":"Respir. Res."},{"key":"ref_53","first-page":"5583","article-title":"Carbocistein improves airway remodeling in asthmatic mice","volume":"14","author":"Zhou","year":"2022","journal-title":"Am. J. Transl. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1046\/j.1365-2125.2003.01788.x","article-title":"Effect of carbocysteine on cough reflex to capsaicin in asthmatic patients","volume":"55","author":"Ishiura","year":"2003","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1080\/00016489.2021.1991592","article-title":"The relationship between Covid-19 and mucociliary clearance","volume":"141","author":"Kahraman","year":"2021","journal-title":"Acta Oto-Laryngologica"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00424-018-2212-2","article-title":"Carbocysteine stimulated an increase in ciliary bend angle via a decrease in [Cl\u2212]i in mouse airway cilia","volume":"471","author":"Ikeuchi","year":"2019","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_57","first-page":"17","article-title":"Effects of Carbocysteine on airway inflammation and related events in SO2-exposed rats","volume":"39","author":"Ishibashi","year":"2001","journal-title":"Nihon Kokyuki Gakkai Zasshi"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.resp.2011.10.017","article-title":"l-Carbocysteine inhibits respiratory syncytial virus infection in human tracheal epithelial cells","volume":"180","author":"Asada","year":"2012","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1378\/chest.100.5.1377","article-title":"Respiratory Syncytial Virus Infection among Intubated Adults in a University Medical Intensive Care Unit","volume":"100","author":"Guidry","year":"1991","journal-title":"Chest"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"L160","DOI":"10.1152\/ajplung.00376.2009","article-title":"Inhibitory effects of Carbocysteine on type A seasonal influenza virus infection in human airway epithelial cells","volume":"299","author":"Yamaya","year":"2010","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"16292","DOI":"10.1021\/acsomega.0c02125","article-title":"Impact of Thiol\u2013Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin-Converting Enzyme 2 Receptor","volume":"5","author":"Hati","year":"2020","journal-title":"ACS Omega"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ferraro, M., Di Vincenzo, S., Sangiorgi, C., Leto Barone, S., Gangemi, S., Lanata, L., and Pace, E. (2022). Carbocysteine Modifies Circulating miR-21, IL-8, sRAGE, and fAGEs Levels in Mild Acute Exacerbated COPD Patients: A Pilot Study. Pharmaceuticals, 15.","DOI":"10.3390\/ph15020218"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-3-319-63245-2_8","article-title":"ROS Signaling in the Pathogenesis of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS)","volume":"967","author":"Kellner","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1440-1843.2008.01424.x","article-title":"Carbocysteine can scavenge reactive oxygen species in vitro","volume":"14","author":"Nogawa","year":"2009","journal-title":"Respirology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1038\/s41591-021-01500-9","article-title":"Calming the cytokine storm in COVID-19","volume":"27","author":"Cron","year":"2021","journal-title":"Nat. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial cell infection and endotheliitis in COVID-19","volume":"395","author":"Varga","year":"2020","journal-title":"Lancet"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.thromres.2019.07.013","article-title":"The stimulation of thrombosis by hypoxia","volume":"181","author":"Gupta","year":"2019","journal-title":"Thromb. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/s41577-020-0407-1","article-title":"Tissue damage from neutrophil-induced oxidative stress in COVID-19","volume":"20","author":"Laforge","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.niox.2020.06.002","article-title":"Tackle the free radicals damage in COVID-19","volume":"102","author":"Wu","year":"2020","journal-title":"Nitric Oxide"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Bakadia, B.M., Boni, B.O.O., Ahmed, A.A.Q., and Yang, G. (2020). The impact of oxidative stress damage induced by the environmental stressors on COVID-19. Life Sci., 264.","DOI":"10.1016\/j.lfs.2020.118653"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/jmv.26406","article-title":"Elevated MUC1 and MUC5AC mucin protein levels in airway mucus of critical ill COVID-19 patients","volume":"93","author":"Lu","year":"2021","journal-title":"J. Med Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1007\/s13238-020-00752-4","article-title":"Single-cell analysis reveals bronchoalveolar epithelial dysfunction in COVID-19 patients","volume":"11","author":"He","year":"2020","journal-title":"Protein Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1097\/SLA.0000000000004031","article-title":"Tracheobronchial Slough, a Potential Pathology in Endotracheal Tube Obstruction in Patients with Coronavirus Disease 2019 (COVID-19) in the Intensive Care Setting","volume":"272","author":"Rubano","year":"2020","journal-title":"Ann. Surg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1177\/0885066620981891","article-title":"Endotracheal Tube Obstruction Among Patients Mechanically Ventilated for ARDS Due to COVID-19: A Case Series","volume":"36","author":"Wiles","year":"2020","journal-title":"J. Intensiv. Care Med."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Manckoundia, P., and Franon, E. (2020). Is Persistent Thick Copious Mucus a Long-Term Symptom of COVID-19?. Eur. J. Case Rep. Intern. Med., 7.","DOI":"10.12890\/2020_002145"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.jiph.2020.07.003","article-title":"Molecular pathogenesis of secondary bacterial infection associated to viral infections including SARS-CoV-2","volume":"13","author":"Manna","year":"2020","journal-title":"J. Infect. Publ. Health"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Kato, T., Asakura, T., E Edwards, C., Dang, H., Mikami, Y., Okuda, K., Chen, G., Sun, L., Gilmore, R.C., and Hawkins, P. (2022). Prevalence and Mechanisms of Mucus Accumulation in COVID-19 Lung Disease. Am. J. Respir. Crit. Care Med., Epub ahead of print.","DOI":"10.1164\/rccm.202111-2606OC"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1056\/NEJMoa2021436","article-title":"Dexamethasone in Hospitalized Patients with Covid-19","volume":"384","author":"Horby","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.2147\/TCRM.S273700","article-title":"N-Acetylcysteine to Combat COVID-19: An Evidence Review","volume":"16","author":"Shi","year":"2020","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Iciek, M., Bilska-Wilkosz, A., Kozdrowicki, M., and G\u00f3rny, M. (2022). Reactive Sulfur Compounds in the Fight against COVID-19. Antioxidants, 11.","DOI":"10.3390\/antiox11061053"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1080\/23744235.2021.1945675","article-title":"N-acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: A two-center retrospective cohort study","volume":"53","author":"Assimakopoulos","year":"2021","journal-title":"Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Foschi, C., Zignoli, A., Gaibani, P., Vocale, C., Rossini, G., Lafratta, S., Liberatore, A., Turello, G., Lazzarotto, T., and Ambretti, S. (2021). Respiratory bacterial co-infections in intensive care unit-hospitalized COVID-19 patients: Conventional culture vs BioFire FilmArray pneumonia Plus panel. J. Microbiol. Methods, 186.","DOI":"10.1016\/j.mimet.2021.106259"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.rmed.2016.06.015","article-title":"The effect of N -acetylcysteine on biofilms: Implications for the treatment of respiratory tract infections","volume":"117","author":"Blasi","year":"2016","journal-title":"Respir. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1007\/s40265-020-01412-x","article-title":"Multifaceted Beneficial Effects of Erdosteine: More than a Mucolytic Agent","volume":"80","author":"Cazzola","year":"2020","journal-title":"Drugs"},{"key":"ref_85","first-page":"344","article-title":"Effects of Erdosteine and Its Metabolites on Bacterial Adhesiveness","volume":"49","author":"Braga","year":"1999","journal-title":"Arzneimittelforschung"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1159\/000063223","article-title":"Bacterial Adhesiveness: Effects of the SH Metabolite of Erdosteine (Mucoactive Drug) plus Clarithromycin versus Clarithromycin Alone","volume":"47","author":"Braga","year":"2001","journal-title":"Chemotherapy"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.pupt.2017.11.009","article-title":"Impact of erdosteine on chronic bronchitis and COPD: A meta-analysis","volume":"48","author":"Cazzola","year":"2018","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_88","unstructured":"(2022, May 23). Recipharm\u2019s Proprietary Molecule Erdosteine Has Been Positively Tested as Part of COVID-19 Treatment. Available online: https:\/\/mb.cision.com\/Main\/9273\/3215696\/1318818.pdf."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/11\/1824\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:12:47Z","timestamp":1760145167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/11\/1824"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,8]]},"references-count":88,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["life12111824"],"URL":"https:\/\/doi.org\/10.3390\/life12111824","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,8]]}}}