Clinical efficacy of inhaled corticosteroids in patients with coronavirus disease 2019: A living review and meta-analysis

{ 'indexed': { 'date-parts': [[2023, 11, 29]], 'date-time': '2023-11-29T01:04:12Z', 'timestamp': 1701219852810}, 'reference-count': 38, 'publisher': 'Public Library of Science (PLoS)', 'issue': '11', 'license': [ { 'start': { 'date-parts': [[2023, 11, 28]], 'date-time': '2023-11-28T00:00:00Z', 'timestamp': 1701129600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'funder': [ { 'DOI': '10.13039/501100003670', 'name': 'National Evidence-based Healthcare Collaborating Agency', 'doi-asserted-by': 'publisher', 'award': ['NECA-P-21-004']}, { 'DOI': '10.13039/501100003670', 'name': 'National Evidence-based Healthcare Collaborating Agency', 'doi-asserted-by': 'publisher', 'award': ['NECA-A-22-008']}, { 'DOI': '10.13039/501100003670', 'name': 'National Evidence-based Healthcare Collaborating Agency', 'doi-asserted-by': 'publisher', 'award': ['NECA-A-23-010']}, { 'DOI': '10.13039/501100002510', 'name': 'Kongju National University', 'doi-asserted-by': 'publisher', 'award': ['2023']}], 'content-domain': {'domain': ['www.plosone.org'], 'crossmark-restriction': False}, 'abstract': '<jats:p>Inhaled corticosteroids are known to be relatively safe for long-term use in ' 'inflammatory respiratory diseases and it has been repurposed as one of the potential ' 'therapies for outpatients with coronavirus disease 2019 (COVID-19). However, inhaled ' 'corticosteroids have not been accepted for COVID-19 as a standard therapy because of its lack ' 'of proven benefits. Therefore, this study aimed to evaluate the effectiveness of inhaled ' 'corticosteroids in patients with COVID-19. Randomized controlled trials comparing the ' 'efficacy of inhaled corticosteroid treatment in patients with COVID-19 were identified ' 'through literature electronic database searches up to March 10, 2023. Meta-analyses were ' 'conducted for predefined outcomes, and the certainty of evidence was graded using the grading ' 'of recommendations, assessment, development, and evaluation approach. Overall, seven trials ' '(eight articles) were included in this systematic review. Compared with usual care, inhaled ' 'corticosteroids was associated with significantly improved clinical recovery at 7 and 14 days ' 'in patients with COVID-19. In subgroup analysis, only budesonide showed significant efficacy ' 'in clinical recovery, whereas no significant benefit was observed for ciclesonide. Moreover, ' 'inhaled corticosteroids use was not significantly associated with all-cause hospitalization, ' 'all-cause mortality, admission to intensive care unit, or the use of mechanical ventilation. ' 'Our systematic review used evidence with very low to moderate certainty. Although based on ' 'limited evidence, our results suggest that inhaled corticosteroids treatment, especially ' 'budesonide, improves the clinical recovery of patients with COVID-19. More trials and ' 'meta-analyses are needed to assess the efficacy of inhaled corticosteroids for COVID-19 ' 'treatment.</jats:p>', 'DOI': '10.1371/journal.pone.0294872', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 11, 28]], 'date-time': '2023-11-28T18:35:04Z', 'timestamp': 1701196504000}, 'page': 'e0294872', 'update-policy': 'http://dx.doi.org/10.1371/journal.pone.corrections_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Clinical efficacy of inhaled corticosteroids in patients with coronavirus disease 2019: A living ' 'review and meta-analysis', 'prefix': '10.1371', 'volume': '18', 'author': [ {'given': 'Su-Yeon', 'family': 'Yu', 'sequence': 'first', 'affiliation': []}, {'given': 'Miyoung', 'family': 'Choi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Seungeun', 'family': 'Ryoo', 'sequence': 'additional', 'affiliation': []}, {'given': 'Chelim', 'family': 'Cheong', 'sequence': 'additional', 'affiliation': []}, {'given': 'Kyungmin', 'family': 'Huh', 'sequence': 'additional', 'affiliation': []}, {'given': 'Young Kyung', 'family': 'Yoon', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-4025-4542', 'authenticated-orcid': True, 'given': 'Su Jin', 'family': 'Jeong', 'sequence': 'additional', 'affiliation': []}], 'member': '340', 'published-online': {'date-parts': [[2023, 11, 28]]}, 'reference': [ { 'issue': '8', 'key': 'pone.0294872.ref001', 'doi-asserted-by': 'crossref', 'first-page': '727', 'DOI': '10.1056/NEJMoa2001017', 'article-title': 'A Novel Coronavirus from Patients with Pneumonia in China, 2019', 'volume': '382', 'author': 'N Zhu', 'year': '2020', 'journal-title': 'New England Journal of Medicine'}, { 'issue': '8', 'key': 'pone.0294872.ref002', 'doi-asserted-by': 'crossref', 'first-page': '693', 'DOI': '10.1056/NEJMoa2021436', 'article-title': 'Dexamethasone in Hospitalized Patients with Covid-19', 'volume': '384', 'author': 'P Horby', 'year': '2021', 'journal-title': 'New England Journal of Medicine'}, { 'issue': '13', 'key': 'pone.0294872.ref003', 'doi-asserted-by': 'crossref', 'first-page': '1330', 'DOI': '10.1001/jama.2020.17023', 'article-title': 'Association Between Administration of Systemic Corticosteroids and ' 'Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis', 'volume': '324', 'author': 'JAC Sterne', 'year': '2020', 'journal-title': 'JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION'}, { 'issue': '6', 'key': 'pone.0294872.ref004', 'doi-asserted-by': 'crossref', 'first-page': '321', 'DOI': '10.1159/000091126', 'article-title': 'Nuclear factor-kappaB- and glucocorticoid receptor alpha- mediated ' 'mechanisms in the regulation of systemic and pulmonary inflammation ' 'during sepsis and acute respiratory distress syndrome. Evidence for ' 'inflammation-induced target tissue resistance to glucocorticoids', 'volume': '12', 'author': 'GU Meduri', 'year': '2005', 'journal-title': 'Neuroimmunomodulation'}, { 'issue': '3', 'key': 'pone.0294872.ref005', 'first-page': '1223', 'article-title': 'Cytokine Indexes in Pemphigus Vulgaris: Perception of Its ' 'Immunpathogenesis and Hopes for Non-Steroidal Treatment', 'volume': '16', 'author': 'M Masjedi', 'year': '2017', 'journal-title': 'Iranian journal of pharmaceutical research'}, { 'key': 'pone.0294872.ref006', 'doi-asserted-by': 'crossref', 'first-page': '103492', 'DOI': '10.1016/j.resp.2020.103492', 'article-title': 'Pros and cons of corticosteroid therapy for COVID-19 patients', 'volume': '280', 'author': 'P Mattos-Silva', 'year': '2020', 'journal-title': 'Respiratory Physiology & Neurobiology'}, { 'key': 'pone.0294872.ref007', 'doi-asserted-by': 'crossref', 'first-page': '106563', 'DOI': '10.1016/j.clineuro.2021.106563', 'article-title': 'Can pulse steroid therapy increase the risk of infection by COVID-19 in ' 'patients with multiple sclerosis?', 'volume': '203', 'author': 'AN Moghadasi', 'year': '2021', 'journal-title': 'Clinical Neurology and Neurosurgery'}, { 'issue': '11', 'key': 'pone.0294872.ref008', 'doi-asserted-by': 'crossref', 'first-page': '887', 'DOI': '10.1001/jama.1997.03540350037030', 'article-title': 'Inhaled steroids and the risk of hospitalization for asthma', 'volume': '277', 'author': 'JG Donahue', 'year': '1997', 'journal-title': 'JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION'}, { 'issue': '1', 'key': 'pone.0294872.ref009', 'doi-asserted-by': 'crossref', 'DOI': '10.1183/13993003.00130-2021', 'article-title': 'Inhaled corticosteroids downregulate SARS-CoV-2-related genes in COPD: ' 'results from a randomised controlled trial', 'volume': '58', 'author': 'S Milne', 'year': '2021', 'journal-title': 'Eur Respir J'}, { 'issue': '1', 'key': 'pone.0294872.ref010', 'doi-asserted-by': 'crossref', 'first-page': '83', 'DOI': '10.1164/rccm.202003-0821OC', 'article-title': 'COVID-19-related Genes in Sputum Cells in Asthma. Relationship to ' 'Demographic Features and Corticosteroids', 'volume': '202', 'author': 'MC Peters', 'year': '2020', 'journal-title': 'Am J Respir Crit Care Med'}, { 'issue': '19', 'key': 'pone.0294872.ref011', 'doi-asserted-by': 'crossref', 'first-page': '2047', 'DOI': '10.1001/archinte.167.19.2047', 'article-title': 'Adverse effects of inhaled corticosteroids in funded and nonfunded ' 'studies', 'volume': '167', 'author': 'A Nieto', 'year': '2007', 'journal-title': 'Archives of Internal Medicine (1960)'}, { 'issue': '6', 'key': 'pone.0294872.ref012', 'doi-asserted-by': 'crossref', 'first-page': '380', 'DOI': '10.7326/0003-4819-149-6-200809160-00004', 'article-title': 'Risk for death associated with medications for recently diagnosed ' 'chronic obstructive pulmonary disease', 'volume': '149', 'author': 'TA Lee', 'year': '2008', 'journal-title': 'Annals of Internal Medicine'}, { 'issue': '10', 'key': 'pone.0294872.ref013', 'doi-asserted-by': 'crossref', 'first-page': 'e1', 'DOI': '10.1016/j.jclinepi.2009.06.006', 'article-title': 'The PRISMA statement for reporting systematic reviews and meta-analyses ' 'of studies that evaluate health care interventions: explanation and ' 'elaboration', 'volume': '62', 'author': 'A Liberati', 'year': '2009', 'journal-title': 'Journal of clinical epidemiology'}, { 'key': 'pone.0294872.ref014', 'first-page': 'Ed000142', 'article-title': 'Updated guidance for trusted systematic reviews: a new edition of the ' 'Cochrane Handbook for Systematic Reviews of Interventions', 'volume': '10', 'author': 'M Cumpston', 'year': '2019', 'journal-title': 'Cochrane Database Syst Rev'}, { 'issue': '2', 'key': 'pone.0294872.ref015', 'doi-asserted-by': 'crossref', 'first-page': '173', 'DOI': '10.1016/j.jclinepi.2012.08.001', 'article-title': 'GRADE guidelines: 13. Preparing summary of findings tables and evidence ' 'profiles-continuous outcomes', 'volume': '66', 'author': 'GH Guyatt', 'year': '2013', 'journal-title': 'J Clin Epidemiol'}, { 'issue': '7', 'key': 'pone.0294872.ref016', 'doi-asserted-by': 'crossref', 'first-page': '763', 'DOI': '10.1016/S2213-2600(21)00160-0', 'article-title': 'Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase ' '2, open-label, randomised controlled trial', 'volume': '9', 'author': 'S Ramakrishnan', 'year': '2021', 'journal-title': 'The Lancet Respiratory Medicine'}, { 'issue': '10303', 'key': 'pone.0294872.ref017', 'doi-asserted-by': 'crossref', 'first-page': '843', 'DOI': '10.1016/S0140-6736(21)01744-X', 'article-title': 'Inhaled budesonide for COVID-19 in people at high risk of complications ' 'in the community in the UK (PRINCIPLE): a randomised, controlled, ' 'open-label, adaptive platform trial', 'volume': '398', 'author': 'L-M Yu', 'year': '2021', 'journal-title': 'Lancet'}, { 'issue': '5', 'key': 'pone.0294872.ref018', 'doi-asserted-by': 'crossref', 'first-page': '225', 'DOI': '10.5582/ddt.2022.01068', 'article-title': 'Impact of inhaled ciclesonide on asymptomatic or mild COVID-19: A ' 'randomized trial', 'volume': '16', 'author': 'J Terada-Hirashima', 'year': '2022', 'journal-title': 'Drug Discov Ther'}, { 'issue': '1', 'key': 'pone.0294872.ref019', 'doi-asserted-by': 'crossref', 'first-page': '42', 'DOI': '10.1001/jamainternmed.2021.6759', 'article-title': 'Efficacy of inhaled ciclesonide for outpatient treatment of adolescents ' 'and adults with symptomatic COVID-19: a randomized clinical trial', 'volume': '182', 'author': 'BM Clemency', 'year': '2022', 'journal-title': 'JAMA internal medicine'}, { 'key': 'pone.0294872.ref020', 'article-title': 'Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at ' 'risk of adverse outcomes: a randomised controlled trial (COVERAGE)', 'author': 'A Duvignaud', 'year': '2022', 'journal-title': 'Clinical Microbiology and Infection'}, { 'key': 'pone.0294872.ref021', 'first-page': '375', 'article-title': 'Inhaled and intranasal ciclesonide for the treatment of covid-19 in ' 'adult outpatients: CONTAIN phase II randomised controlled trial', 'author': 'N Ezer', 'year': '2021', 'journal-title': 'BMJ (Clinical Research ed.)'}, { 'issue': '16', 'key': 'pone.0294872.ref022', 'doi-asserted-by': 'crossref', 'first-page': '3545', 'DOI': '10.3390/jcm10163545', 'article-title': 'Ciclesonide inhaler treatment for mild-to-moderate COVID-19: a ' 'randomized, open-label, phase 2 trial', 'volume': '10', 'author': 'J-Y Song', 'year': '2021', 'journal-title': 'Journal of Clinical Medicine'}, { 'issue': '2', 'key': 'pone.0294872.ref023', 'doi-asserted-by': 'crossref', 'first-page': 'e064374', 'DOI': '10.1136/bmjopen-2022-064374', 'article-title': 'Inhaled ciclesonide in adults hospitalised with COVID-19: a randomised ' 'controlled open-label trial (HALT COVID-19)', 'volume': '13', 'author': 'D Brodin', 'year': '2023', 'journal-title': 'BMJ open'}, { 'issue': '3', 'key': 'pone.0294872.ref024', 'article-title': 'Inhaled corticosteroids for the treatment of COVID‐19', 'author': 'M Griesel', 'year': '2022', 'journal-title': 'Cochrane Database of Systematic Reviews (Online)'}, { 'issue': '1', 'key': 'pone.0294872.ref025', 'doi-asserted-by': 'crossref', 'first-page': '1S', 'DOI': '10.1378/chest.129.1_suppl.1S', 'article-title': 'Diagnosis and management of cough executive summary: ACCP ' 'evidence-based clinical practice guidelines', 'volume': '129', 'author': 'RS Irwin', 'year': '2006', 'journal-title': 'Chest'}, { 'issue': '5', 'key': 'pone.0294872.ref026', 'doi-asserted-by': 'crossref', 'first-page': '403', 'DOI': '10.1136/thx.54.5.403', 'article-title': 'Effect of inhaled steroids on airway hyperresponsiveness, sputum ' 'eosinophils, and exhaled nitric oxide levels in patients with asthma', 'volume': '54', 'author': 'EL van Rensen', 'year': '1999', 'journal-title': 'Thorax'}, { 'issue': '3', 'key': 'pone.0294872.ref027', 'article-title': 'Inhaled steroids and risk of pneumonia for chronic obstructive ' 'pulmonary disease', 'author': 'KM Kew', 'year': '2014', 'journal-title': 'Cochrane Database of Systematic Reviews (Online)'}, { 'issue': '1', 'key': 'pone.0294872.ref028', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1038/s41467-018-04574-1', 'article-title': 'Corticosteroid suppression of antiviral immunity increases bacterial ' 'loads and mucus production in COPD exacerbations', 'volume': '9', 'author': 'A Singanayagam', 'year': '2018', 'journal-title': 'Nature Communications'}, { 'key': 'pone.0294872.ref029', 'doi-asserted-by': 'crossref', 'first-page': '154857', 'DOI': '10.1016/j.cyto.2019.154857', 'article-title': 'Increased type 2 inflammation post rhinovirus infection in patients ' 'with moderate asthma', 'volume': '125', 'author': 'T Southworth', 'year': '2020', 'journal-title': 'Cytokine'}, { 'key': 'pone.0294872.ref030', 'doi-asserted-by': 'crossref', 'first-page': '44', 'DOI': '10.1016/j.pupt.2014.10.006', 'article-title': 'Differences in the efficacy and safety among inhaled corticosteroids ' '(ICS)/long-acting beta2-agonists (LABA) combinations in the treatment ' 'of chronic obstructive pulmonary disease (COPD): role of ICS', 'volume': '30', 'author': 'M Latorre', 'year': '2015', 'journal-title': 'Pulmonary Pharmacology & Therapeutics'}, { 'issue': '3', 'key': 'pone.0294872.ref031', 'doi-asserted-by': 'crossref', 'first-page': '519', 'DOI': '10.1345/aph.1L546', 'article-title': 'Comparison of inhaled corticosteroids: an update', 'volume': '43', 'author': 'HW Kelly', 'year': '2009', 'journal-title': 'ANNALS OF PHARMACOTHERAPY'}, { 'issue': '3', 'key': 'pone.0294872.ref032', 'doi-asserted-by': 'crossref', 'first-page': '377', 'DOI': '10.1007/s15010-018-1229-y', 'article-title': 'Inhaled corticosteroids and risk of upper respiratory tract infection ' 'in patients with asthma: a meta-analysis', 'volume': '47', 'author': 'M Yang', 'year': '2019', 'journal-title': 'Infection'}, { 'key': 'pone.0294872.ref033', 'doi-asserted-by': 'crossref', 'first-page': '105950', 'DOI': '10.1016/j.intimp.2019.105950', 'article-title': 'Inhaled corticosteroids and risk of pneumonia in patients with chronic ' 'obstructive pulmonary disease: a meta-analysis of randomized controlled ' 'trials', 'volume': '77', 'author': 'M Yang', 'year': '2019', 'journal-title': 'International Immunopharmacology'}, { 'issue': '10', 'key': 'pone.0294872.ref034', 'doi-asserted-by': 'crossref', 'first-page': '1657', 'DOI': '10.1016/j.bcp.2007.01.031', 'article-title': 'The role of esterases in the metabolism of ciclesonide to ' 'desisobutyryl-ciclesonide in human tissue', 'volume': '73', 'author': 'E Mutch', 'year': '2007', 'journal-title': 'Biochemical Pharmacology'}, { 'issue': '4', 'key': 'pone.0294872.ref035', 'doi-asserted-by': 'crossref', 'first-page': '243', 'DOI': '10.2165/00003088-200948040-00002', 'article-title': 'Clinical pharmacokinetic and pharmacodynamic profile of inhaled ' 'ciclesonide', 'volume': '48', 'author': 'R. Nave', 'year': '2009', 'journal-title': 'Clinical Pharmacokinetics'}, { 'issue': '7', 'key': 'pone.0294872.ref036', 'doi-asserted-by': 'crossref', 'first-page': 'e00819', 'DOI': '10.1128/AAC.00819-20', 'article-title': 'Identification of antiviral drug candidates against SARS-CoV-2 from ' 'FDA-approved drugs', 'volume': '64', 'author': 'S Jeon', 'year': '2020', 'journal-title': 'Antimicrobial Agents and Chemotherapy'}, { 'issue': '1', 'key': 'pone.0294872.ref037', 'doi-asserted-by': 'crossref', 'first-page': 'e01648', 'DOI': '10.1128/JVI.01648-20', 'article-title': 'The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by ' 'targeting the viral replication-transcription complex in cultured cells', 'volume': '95', 'author': 'S Matsuyama', 'year': '2020', 'journal-title': 'Journal of Virology'}, { 'issue': '4', 'key': 'pone.0294872.ref038', 'article-title': 'Frequent occurrence of mutations in nsp3 and nsp4 of SARS-CoV-2, ' 'presumably caused by the inhaled asthma drug ciclesonide', 'volume': '1', 'author': 'A Doi', 'year': '2022', 'journal-title': 'PNAS Nexus'}], 'container-title': 'PLOS ONE', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://dx.plos.org/10.1371/journal.pone.0294872', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 11, 28]], 'date-time': '2023-11-28T18:35:29Z', 'timestamp': 1701196529000}, 'score': 1, 'resource': {'primary': {'URL': 'https://dx.plos.org/10.1371/journal.pone.0294872'}}, 'subtitle': [], 'editor': [{'given': 'Francis John', 'family': 'Gilchrist', 'sequence': 'first', 'affiliation': []}], 'short-title': [], 'issued': {'date-parts': [[2023, 11, 28]]}, 'references-count': 38, 'journal-issue': {'issue': '11', 'published-online': {'date-parts': [[2023, 11, 28]]}}, 'URL': 'http://dx.doi.org/10.1371/journal.pone.0294872', 'relation': {}, 'ISSN': ['1932-6203'], 'subject': ['Multidisciplinary'], 'container-title-short': 'PLoS ONE', 'published': {'date-parts': [[2023, 11, 28]]}}