Cyclooxygenase inhibitor use is associated with increased COVID-19 severity

{ 'institution': [{'name': 'medRxiv'}], 'indexed': {'date-parts': [[2022, 8, 25]], 'date-time': '2022-08-25T04:19:55Z', 'timestamp': 1661401195366}, 'posted': {'date-parts': [[2021, 4, 20]]}, 'group-title': 'Infectious Diseases (except HIV/AIDS)', 'reference-count': 38, 'publisher': 'Cold Spring Harbor Laboratory', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2021, 12, 22]]}, 'abstract': '<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Non-steroidal ' 'anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation ' 'but have been associated with complications in community-acquired pneumonia. Observations ' 'shortly after the start of the COVID-19 pandemic in 2020 suggested that ibuprofen was ' 'associated with an increased risk of adverse events in COVID-19 patients, but subsequent ' 'observational studies failed to demonstrate increased risk and in one case showed reduced ' 'risk associated with NSAID ' 'use.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A 38-center ' 'retrospective cohort study was performed that leveraged the harmonized, high-granularity ' 'electronic health record data of the National COVID Cohort Collaborative. A ' 'propensity-matched cohort of COVID-19 inpatients was constructed by matching cases (treated ' 'with NSAIDs) and controls (not treated) from 857,061 patients with COVID-19. The primary ' 'outcome of interest was COVID-19 severity in hospitalized patients, which was classified as: ' 'moderate, severe, or mortality/hospice. Secondary outcomes were acute kidney injury (AKI), ' 'extracorporeal membrane oxygenation (ECMO), invasive ventilation, and all-cause mortality at ' 'any time following COVID-19 ' 'diagnosis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Logistic ' 'regression showed that NSAID use was not associated with increased COVID-19 severity (OR: ' '0.57 95% CI: 0.53-0.61). Analysis of secondary outcomes using logistic regression showed that ' 'NSAID use was not associated with increased risk of all-cause mortality (OR 0.51 95% CI: ' '0.47-0.56), invasive ventilation (OR: 0.59 95% CI: 0.55-0.64), AKI (OR: 0.67 95% CI: ' '0.63-0.72), or ECMO (OR: 0.51 95% CI: 0.36-0.7). In contrast, the odds ratios indicate ' 'reduced risk of these outcomes, but our quantitative bias analysis showed E-values of between ' '1.9 and 3.3 for these associations, indicating that comparatively weak or moderate confounder ' 'associations could explain away the observed ' 'associations.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Study ' 'interpretation is limited by the observational design. Recording of NSAID use may have been ' 'incomplete. Our study demonstrates that NSAID use is not associated with increased COVID-19 ' 'severity, all-cause mortality, invasive ventilation, AKI, or ECMO in COVID-19 inpatients. A ' 'conservative interpretation in light of the quantitative bias analysis is that there is no ' 'evidence that NSAID use is associated with risk of increased severity or the other measured ' 'outcomes. Our findings are the largest EHR-based analysis of the effect of NSAIDs on outcome ' 'in COVID-19 patients to date. Our results confirm and extend analogous findings in previous ' 'observational studies using a large cohort of patients drawn from 38 centers in a nationally ' 'representative multicenter database.</jats:p></jats:sec>', 'DOI': '10.1101/2021.04.13.21255438', 'type': 'posted-content', 'created': {'date-parts': [[2021, 4, 21]], 'date-time': '2021-04-21T05:21:18Z', 'timestamp': 1618982478000}, 'source': 'Crossref', 'is-referenced-by-count': 8, 'title': 'NSAID use and clinical outcomes in COVID-19 patients: A 38-center retrospective cohort study', 'prefix': '10.1101', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-2170-2250', 'authenticated-orcid': False, 'given': 'Justin T.', 'family': 'Reese', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-4422-1708', 'authenticated-orcid': False, 'given': 'Ben', 'family': 'Coleman', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-7463-6306', 'authenticated-orcid': False, 'given': 'Lauren', 'family': 'Chan', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-4557-5492', 'authenticated-orcid': False, 'given': 'Hannah', 'family': 'Blau', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-8169-9049', 'authenticated-orcid': False, 'given': 'Tiffany J.', 'family': 'Callahan', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-1269-2038', 'authenticated-orcid': False, 'given': 'Luca', 'family': 'Cappelletti', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-9806-3493', 'authenticated-orcid': False, 'given': 'Tommaso', 'family': 'Fontana', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-9730-1808', 'authenticated-orcid': False, 'given': 'Katie Rebecca', 'family': 'Bradwell', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-6315-3707', 'authenticated-orcid': False, 'given': 'Nomi L.', 'family': 'Harris', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-2024-7572', 'authenticated-orcid': False, 'given': 'Elena', 'family': 'Casiraghi', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-5694-3919', 'authenticated-orcid': False, 'given': 'Giorgio', 'family': 'Valentini', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-1653-8206', 'authenticated-orcid': False, 'given': 'Guy', 'family': 'Karlebach', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-6307-5227', 'authenticated-orcid': False, 'given': 'Rachel', 'family': 'Deer', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-9353-5498', 'authenticated-orcid': False, 'given': 'Julie A.', 'family': 'McMurry', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-9114-8737', 'authenticated-orcid': False, 'given': 'Melissa A.', 'family': 'Haendel', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-5437-2545', 'authenticated-orcid': False, 'given': 'Christopher G.', 'family': 'Chute', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-6840-9756', 'authenticated-orcid': False, 'given': 'Emily', 'family': 'Pfaff', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-2723-5902', 'authenticated-orcid': False, 'given': 'Richard', 'family': 'Moffitt', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-9420-5028', 'authenticated-orcid': False, 'given': 'Heidi', 'family': 'Spratt', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-3485-0006', 'authenticated-orcid': False, 'given': 'Jasvinder', 'family': 'Singh', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-6601-2165', 'authenticated-orcid': False, 'given': 'Christopher J.', 'family': 'Mungall', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-0692-412X', 'authenticated-orcid': False, 'given': 'Andrew E.', 'family': 'Williams', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-0736-9199', 'authenticated-orcid': False, 'given': 'Peter N.', 'family': 'Robinson', 'sequence': 'additional', 'affiliation': []}], 'member': '246', 'reference': [ { 'key': '2021122406050511000_2021.04.13.21255438v2.1', 'unstructured': 'COVID-19 Map - Johns Hopkins Coronavirus Resource Center [Internet]. 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