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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality 9% Improvement Relative Risk Severe case -303% Ibuprofen for COVID-19  Reese et al.  Prophylaxis Is prophylaxis with ibuprofen beneficial for COVID-19? PSM retrospective 11,474 patients in the USA Higher severe cases with ibuprofen (p<0.000001) Reese et al., medRxiv, April 2021 Favors ibuprofen Favors control

Cyclooxygenase inhibitor use is associated with increased COVID-19 severity

Reese et al., medRxiv, doi:10.1101/2021.04.13.21255438
Apr 2021  
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N3C retrospective 250,533 patients showing higher COVID-19 severity with ibuprofen use. Note that results for individual treatments are not included in the journal version or v2 of this preprint.
Study covers ibuprofen, aspirin, and acetaminophen.
risk of death, 9.0% lower, HR 0.91, p = 0.65, treatment 5,737, control 5,737, propensity score matching, Cox proportional hazards, Table S56.
risk of severe case, 303.0% higher, OR 4.03, p < 0.001, treatment 5,737, control 5,737, propensity score matching, Table S48, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Reese et al., 20 Apr 2021, retrospective, USA, preprint, 23 authors.
This PaperIbuprofenAll
{ 'DOI': '10.1101/2021.04.13.21255438', 'URL': '', '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>', 'accepted': {'date-parts': [[2021, 12, 22]]}, 'author': [ { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Reese', 'given': 'Justin T.', 'sequence': 'first'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Coleman', 'given': 'Ben', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Chan', 'given': 'Lauren', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Blau', 'given': 'Hannah', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Callahan', 'given': 'Tiffany J.', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Cappelletti', 'given': 'Luca', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Fontana', 'given': 'Tommaso', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Bradwell', 'given': 'Katie Rebecca', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Harris', 'given': 'Nomi L.', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Casiraghi', 'given': 'Elena', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Valentini', 'given': 'Giorgio', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Karlebach', 'given': 'Guy', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Deer', 'given': 'Rachel', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'McMurry', 'given': 'Julie A.', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Haendel', 'given': 'Melissa A.', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Chute', 'given': 'Christopher G.', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Pfaff', 'given': 'Emily', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Moffitt', 'given': 'Richard', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Spratt', 'given': 'Heidi', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Singh', 'given': 'Jasvinder', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Mungall', 'given': 'Christopher J.', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Williams', 'given': 'Andrew E.', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Robinson', 'given': 'Peter N.', 'sequence': 'additional'}], 'container-title': [], 'content-domain': {'crossmark-restriction': False, 'domain': []}, 'created': {'date-parts': [[2021, 4, 21]], 'date-time': '2021-04-21T05:21:18Z', 'timestamp': 1618982478000}, 'deposited': { 'date-parts': [[2021, 12, 24]], 'date-time': '2021-12-24T14:05:33Z', 'timestamp': 1640354733000}, 'group-title': 'Infectious Diseases (except HIV/AIDS)', 'indexed': {'date-parts': [[2022, 8, 25]], 'date-time': '2022-08-25T04:19:55Z', 'timestamp': 1661401195366}, 'institution': [{'name': 'medRxiv'}], 'is-referenced-by-count': 8, 'issued': {'date-parts': [[2021, 4, 20]]}, 'link': [ { 'URL': '', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'member': '246', 'original-title': [], 'posted': {'date-parts': [[2021, 4, 20]]}, 'prefix': '10.1101', 'published': {'date-parts': [[2021, 4, 20]]}, 'publisher': 'Cold Spring Harbor Laboratory', 'reference': [ { 'key': '2021122406050511000_2021.04.13.21255438v2.1', 'unstructured': 'COVID-19 Map - Johns Hopkins Coronavirus Resource Center [Internet]. 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