Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study

{ 'indexed': {'date-parts': [[2022, 8, 26]], 'date-time': '2022-08-26T15:51:11Z', 'timestamp': 1661529071720}, 'reference-count': 35, 'publisher': 'Oxford University Press (OUP)', 'issue': '11', 'license': [ { 'start': { 'date-parts': [[2020, 7, 27]], 'date-time': '2020-07-27T00:00:00Z', 'timestamp': 1595808000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2021, 12, 6]]}, 'abstract': '<jats:title>Abstract</jats:title>\n' ' <jats:sec>\n' ' <jats:title>Background</jats:title>\n' ' <jats:p>Nonsteroidal antiinflammatory drugs (NSAIDs) may exacerbate ' 'coronavirus disease 2019 (COVID-19) and worsen associated outcomes by upregulating the enzyme ' 'that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to in order to enter ' 'cells.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>We conducted a cohort study using South Korea’s nationwide ' 'healthcare database, which contains data for all individuals who received a COVID-19 test (n ' '= 69 793) as of 8 April 2020. We identified adults hospitalized with COVID-19, where cohort ' 'entry was the date of hospitalization. NSAID users were those prescribed NSAIDs in the 7 days ' 'before and including cohort entry, and nonusers were those not prescribed NSAIDs during this ' 'period. Our primary outcome was a composite of in-hospital death, intensive care unit ' 'admission, mechanical ventilation use, and sepsis; our secondary outcomes were cardiovascular ' 'complications and acute renal failure. We conducted logistic regression analysis to estimate ' 'odds ratio (OR) with 95% confidence intervals (CIs) using inverse probability of treatment ' 'weighting to minimize confounding.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>Of 1824 adults hospitalized with COVID-19 (mean age, 49.0 years; ' 'female, 59%), 354 were NSAID users and 1470 were nonusers. Compared with nonuse, NSAID use ' 'was associated with increased risks of the primary composite outcome (OR, 1.54; 95% CI, ' '1.13–2.11) but insignificantly associated with cardiovascular complications (OR, 1.54; 95% ' 'CI, 0.96–2.48) or acute renal failure (OR, 1.45; 95% CI, 0.49–4.14).</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Conclusions</jats:title>\n' ' <jats:p>While awaiting the results of confirmatory studies, we suggest ' 'NSAIDs be used with caution for COVID-19 patients as the harms associated with their use may ' 'outweigh their benefits.</jats:p>\n' ' </jats:sec>', 'DOI': '10.1093/cid/ciaa1056', 'type': 'journal-article', 'created': {'date-parts': [[2020, 7, 22]], 'date-time': '2020-07-22T19:22:47Z', 'timestamp': 1595445767000}, 'page': 'e4179-e4188', 'source': 'Crossref', 'is-referenced-by-count': 10, 'title': 'Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among ' 'Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study', 'prefix': '10.1093', 'volume': '73', 'author': [ { 'given': 'Han Eol', 'family': 'Jeong', 'sequence': 'first', 'affiliation': [ { 'name': 'Department of Clinical and Social Pharmacy, School of Pharmacy, ' 'Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea'}]}, { 'given': 'Hyesung', 'family': 'Lee', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Clinical and Social Pharmacy, School of Pharmacy, ' 'Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea'}]}, { 'given': 'Hyun Joon', 'family': 'Shin', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of General Internal Medicine, Department of Medicine, ' 'Brigham and Women’s Hospital, and Department of Global Health ' 'and Social Medicine, Harvard Medical School, Boston, ' 'Massachusetts, USA'}]}, { 'given': 'Young June', 'family': 'Choe', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Social and Preventive Medicine, Hallym University ' 'College of Medicine, Chuncheon, Gangwon-do, South Korea'}]}, { 'given': 'Kristian B', 'family': 'Filion', 'sequence': 'additional', 'affiliation': [ { 'name': 'Departments of Medicine and of Epidemiology, Biostatistics and ' 'Occupational Health, McGill University, Montreal, Quebec, ' 'Canada'}, { 'name': 'Centre for Clinical Epidemiology, Lady Davis Institute, ' 'Montreal, Quebec, Canada'}]}, { 'ORCID': 'http://orcid.org/0000-0003-1010-7525', 'authenticated-orcid': False, 'given': 'Ju-Young', 'family': 'Shin', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Clinical and Social Pharmacy, School of Pharmacy, ' 'Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea'}, { 'name': 'Department of Clinical Research Design and Evaluation, Samsung ' 'Advanced Institute for Health Sciences & Technology, ' 'Sungkyunkwan University, Seoul, South Korea'}]}], 'member': '286', 'published-online': {'date-parts': [[2020, 7, 27]]}, 'reference': [ {'key': '2021121011170977900_CIT0001', 'author': 'World Health Organization'}, { 'key': '2021121011170977900_CIT0002', 'doi-asserted-by': 'crossref', 'first-page': 'e1', 'DOI': '10.1016/j.jinf.2020.03.006', 'article-title': 'Rapid asymptomatic transmission of COVID-19 during the incubation ' 'period demonstrating strong infectivity in a cluster of youngsters aged ' '16–23 years outside Wuhan and characteristics of young patients with ' 'COVID-19: a prospective contact-tracing study', 'volume': '80', 'author': 'Huang', 'year': '2020', 'journal-title': 'J Infect'}, { 'key': '2021121011170977900_CIT0003', 'doi-asserted-by': 'crossref', 'first-page': 'e21', 'DOI': '10.1016/S2213-2600(20)30116-8', 'article-title': 'Are patients with hypertension and diabetes mellitus at increased risk ' 'for COVID-19 infection?', 'volume': '8', 'author': 'Fang', 'year': '2020', 'journal-title': 'Lancet Respir Med'}, { 'key': '2021121011170977900_CIT0004', 'doi-asserted-by': 'crossref', 'first-page': '271', 'DOI': '10.1016/j.cell.2020.02.052', 'article-title': 'SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a ' 'clinically proven protease inhibitor', 'volume': '181', 'author': 'Hoffmann', 'year': '2020', 'journal-title': 'Cell'}, { 'key': '2021121011170977900_CIT0005', 'doi-asserted-by': 'crossref', 'first-page': '2831', 'DOI': '10.4049/jimmunol.167.5.2831', 'article-title': 'Roles of cyclooxygenase (COX)-1 and COX-2 in prostanoid production by ' 'human endothelial cells: selective up-regulation of prostacyclin ' 'synthesis by COX-2', 'volume': '167', 'author': 'Caughey', 'year': '2001', 'journal-title': 'J Immunol'}, { 'key': '2021121011170977900_CIT0006', 'doi-asserted-by': 'crossref', 'first-page': '525', 'DOI': '10.1086/590499', 'article-title': 'Hyperinduction of cyclooxygenase-2-mediated proinflammatory cascade: a ' 'mechanism for the pathogenesis of avian influenza H5N1 infection', 'volume': '198', 'author': 'Lee', 'year': '2008', 'journal-title': 'J Infect Dis'}, { 'key': '2021121011170977900_CIT0007', 'doi-asserted-by': 'crossref', 'first-page': '558', 'DOI': '10.1080/22221751.2020.1736644', 'article-title': 'A tug-of-war between severe acute respiratory syndrome coronavirus 2 ' 'and host antiviral defence: lessons from other pathogenic viruses', 'volume': '9', 'author': 'Fung', 'year': '2020', 'journal-title': 'Emerg Microbes Infect'}, { 'key': '2021121011170977900_CIT0008', 'volume-title': 'Update–Coronavirus: French health minister and WHO issue warning over ' 'taking anti-inflammatories', 'author': 'Emma', 'year': '2020'}, { 'key': '2021121011170977900_CIT0009', 'volume-title': 'FDA advises patients on use of non-steroidal anti-inflammatory drugs ' '(NSAIDs) for COVID-19', 'author': 'US Food and Drug Administration', 'year': '2020'}, { 'key': '2021121011170977900_CIT0010', 'volume-title': 'EMA gives advice on the use of non-steroidal anti-inflammatories for ' 'COVID-19', 'author': 'European Medicines Agency', 'year': '2020'}, { 'key': '2021121011170977900_CIT0011', 'volume-title': 'No evidence to support claims ibuprofen worsens COVID-19 symptoms', 'author': 'Therapeutic Goods Administration', 'year': '2020'}, { 'key': '2021121011170977900_CIT0012', 'volume-title': 'Scientific Brief: The use of non-steroidal anti-inflammatory drugs ' '(NSAIDs) in patients with COVID-19', 'author': 'World Health Organization', 'year': '2020'}, {'key': '2021121011170977900_CIT0013'}, { 'key': '2021121011170977900_CIT0014', 'doi-asserted-by': 'crossref', 'first-page': '718', 'DOI': '10.3346/jkms.2017.32.5.718', 'article-title': 'Towards actualizing the value potential of Korea Health Insurance ' 'Review and Assessment (HIRA) Data as a resource for health research: ' 'strengths, limitations, applications, and strategies for optimal use of ' 'HIRA data', 'volume': '32', 'author': 'Kim', 'year': '2017', 'journal-title': 'J Korean Med Sci'}, { 'key': '2021121011170977900_CIT0015', 'volume-title': 'Laboratory testing for coronavirus disease 2019 (COVID-19) in suspected ' 'human cases: interim guidance', 'author': 'World Health Organization', 'year': '2020'}, {'key': '2021121011170977900_CIT0016', 'author': 'Ministry of Health and Welfare RoK'}, { 'key': '2021121011170977900_CIT0017', 'doi-asserted-by': 'crossref', 'first-page': '492', 'DOI': '10.1093/aje/kwm324', 'article-title': 'Immortal time bias in pharmaco-epidemiology', 'volume': '167', 'author': 'Suissa', 'year': '2008', 'journal-title': 'Am J Epidemiol'}, { 'key': '2021121011170977900_CIT0018', 'doi-asserted-by': 'crossref', 'first-page': 'l5657', 'DOI': '10.1136/bmj.l5657', 'article-title': 'Alternative approaches for confounding adjustment in observational ' 'studies using weighting based on the propensity score: a primer for ' 'practitioners', 'volume': '367', 'author': 'Desai', 'year': '2019', 'journal-title': 'BMJ'}, { 'key': '2021121011170977900_CIT0019', 'article-title': 'Reducing bias in a propensity score matched-pair sample using greedy ' 'matching techniques.', 'volume-title': 'Proceedings of the Twenty-sixth Annual SAS Users Group International ' 'Conference', 'year': '2001'}, { 'key': '2021121011170977900_CIT0020', 'volume-title': 'Anti-inflammatoires non steroidiens (AINS) et complications infectieuses ' 'graves - Point d’Information', 'author': 'L’Agence nationale de securite du medicament et des produits de sante (ANSM)', 'year': '2019'}, { 'key': '2021121011170977900_CIT0021', 'doi-asserted-by': 'crossref', 'first-page': '786', 'DOI': '10.3390/jcm8060786', 'article-title': 'Risks related to the use of non-steroidal anti-inflammatory drugs in ' 'community-acquired pneumonia in adult and pediatric patients', 'volume': '8', 'author': 'Voiriot', 'year': '2019', 'journal-title': 'J Clin Med'}, { 'key': '2021121011170977900_CIT0022', 'doi-asserted-by': 'crossref', 'article-title': 'Non-steroidal anti-inflammatory drugs and covid-19', 'author': 'Little', 'year': '2020', 'journal-title': 'BMJ', 'DOI': '10.1136/bmj.m1185'}, { 'key': '2021121011170977900_CIT0023', 'doi-asserted-by': 'crossref', 'first-page': '503', 'DOI': '10.1093/infdis/jiw603', 'article-title': 'Acute respiratory infection and use of nonsteroidal anti-inflammatory ' 'drugs on risk of acute myocardial infarction: a nationwide ' 'case-crossover study', 'volume': '215', 'author': 'Wen', 'year': '2017', 'journal-title': 'J Infect Dis'}, { 'key': '2021121011170977900_CIT0024', 'doi-asserted-by': 'crossref', 'first-page': '645', 'DOI': '10.1002/pds.4428', 'article-title': 'Risk of stroke associated with use of nonsteroidal anti-inflammatory ' 'drugs during acute respiratory infection episode', 'volume': '27', 'author': 'Wen', 'year': '2018', 'journal-title': 'Pharmacoepidemiol Drug Saf'}, { 'key': '2021121011170977900_CIT0025', 'doi-asserted-by': 'crossref', 'first-page': '1015', 'DOI': '10.1093/eurheartj/ehv505', 'article-title': 'Cardiovascular safety of non-aspirin non-steroidal anti-inflammatory ' 'drugs: review and position paper by the Working Group for ' 'Cardiovascular Pharmacotherapy of the European Society of Cardiology', 'volume': '37', 'author': 'Schmidt', 'year': '2016', 'journal-title': 'Eur Heart J'}, { 'key': '2021121011170977900_CIT0026', 'doi-asserted-by': 'crossref', 'first-page': '769', 'DOI': '10.1016/S0140-6736(13)60900-9', 'article-title': 'Vascular and upper gastrointestinal effects of non-steroidal ' 'anti-inflammatory drugs: meta-analyses of individual participant data ' 'from randomised trials', 'volume': '382', 'author': 'Bhala', 'year': '2013', 'journal-title': 'Lancet'}, { 'key': '2021121011170977900_CIT0027', 'doi-asserted-by': 'crossref', 'first-page': '520', 'DOI': '10.3389/fped.2019.00520', 'article-title': 'The invisible threat of non-steroidal anti-inflammatory drugs for ' 'kidneys', 'volume': '7', 'author': 'Clavé', 'year': '2017', 'journal-title': 'Front Pediatr'}, { 'key': '2021121011170977900_CIT0028', 'doi-asserted-by': 'crossref', 'first-page': '256', 'DOI': '10.1186/s12882-017-0673-8', 'article-title': 'Non-steroidal anti-inflammatory drug induced acute kidney injury in the ' 'community dwelling general population and people with chronic kidney ' 'disease: systematic review and meta-analysis', 'volume': '18', 'author': 'Zhang', 'year': '2017', 'journal-title': 'BMC Nephrol'}, { 'key': '2021121011170977900_CIT0029', 'doi-asserted-by': 'crossref', 'first-page': '97', 'DOI': '10.1159/000375362', 'article-title': 'Ibuprofen attenuates cardiac fibrosis in streptozotocin-induced ' 'diabetic rats', 'volume': '131', 'author': 'Qiao', 'year': '2015', 'journal-title': 'Cardiology'}, { 'key': '2021121011170977900_CIT0030', 'doi-asserted-by': 'crossref', 'first-page': '450', 'DOI': '10.1038/nature02145', 'article-title': 'Angiotensin-converting enzyme 2 is a functional receptor for the SARS ' 'coronavirus', 'volume': '426', 'author': 'Li', 'year': '2003', 'journal-title': 'Nature'}, { 'key': '2021121011170977900_CIT0031', 'doi-asserted-by': 'crossref', 'first-page': '875', 'DOI': '10.1038/nm1267', 'article-title': 'A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS ' 'coronavirus-induced lung injury', 'volume': '11', 'author': 'Kuba', 'year': '2005', 'journal-title': 'Nat Med'}, { 'key': '2021121011170977900_CIT0032', 'doi-asserted-by': 'crossref', 'first-page': '18', 'DOI': '10.1016/j.cellimm.2009.03.007', 'article-title': 'Ibuprofen and other widely used non-steroidal anti-inflammatory drugs ' 'inhibit antibody production in human cells', 'volume': '258', 'author': 'Bancos', 'year': '2009', 'journal-title': 'Cell Immunol'}, { 'key': '2021121011170977900_CIT0033', 'doi-asserted-by': 'crossref', 'first-page': '981', 'DOI': '10.1111/j.1600-0625.2006.00505.x', 'article-title': 'Non-steroidal anti-inflammatory drugs selectively inhibit cytokine ' 'production by NK cells and gamma delta T cells', 'volume': '15', 'author': 'Inaoka', 'year': '2006', 'journal-title': 'Exp Dermatol'}, { 'key': '2021121011170977900_CIT0034', 'volume-title': 'Evaluation and consideration methods of consistency between health ' 'insurance claims diagnostic codes and medical records', 'author': 'Health Insurance Review and Assessment Service', 'year': '2017'}, { 'key': '2021121011170977900_CIT0035', 'doi-asserted-by': 'crossref', 'first-page': '731', 'DOI': '10.1016/0895-4356(94)90170-8', 'article-title': 'Evidence of the depletion of susceptibles effect in non-experimental ' 'pharmacoepidemiologic research', 'volume': '47', 'author': 'Moride', 'year': '1994', 'journal-title': 'J Clin Epidemiol'}], 'container-title': 'Clinical Infectious Diseases', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'http://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciaa1056/33787343/ciaa1056.pdf', 'content-type': 'application/pdf', 'content-version': 'am', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/cid/article-pdf/73/11/e4179/41608032/ciaa1056.pdf', 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