DOI record:
{
"DOI": "10.1101/2021.04.13.21255438",
"URL": "http://dx.doi.org/10.1101/2021.04.13.21255438",
"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": "http://orcid.org/0000-0002-2170-2250",
"affiliation": [],
"authenticated-orcid": false,
"family": "Reese",
"given": "Justin T.",
"sequence": "first"
},
{
"ORCID": "http://orcid.org/0000-0002-4422-1708",
"affiliation": [],
"authenticated-orcid": false,
"family": "Coleman",
"given": "Ben",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-7463-6306",
"affiliation": [],
"authenticated-orcid": false,
"family": "Chan",
"given": "Lauren",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-4557-5492",
"affiliation": [],
"authenticated-orcid": false,
"family": "Blau",
"given": "Hannah",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-8169-9049",
"affiliation": [],
"authenticated-orcid": false,
"family": "Callahan",
"given": "Tiffany J.",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-1269-2038",
"affiliation": [],
"authenticated-orcid": false,
"family": "Cappelletti",
"given": "Luca",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-9806-3493",
"affiliation": [],
"authenticated-orcid": false,
"family": "Fontana",
"given": "Tommaso",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-9730-1808",
"affiliation": [],
"authenticated-orcid": false,
"family": "Bradwell",
"given": "Katie Rebecca",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0001-6315-3707",
"affiliation": [],
"authenticated-orcid": false,
"family": "Harris",
"given": "Nomi L.",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-2024-7572",
"affiliation": [],
"authenticated-orcid": false,
"family": "Casiraghi",
"given": "Elena",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-5694-3919",
"affiliation": [],
"authenticated-orcid": false,
"family": "Valentini",
"given": "Giorgio",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-1653-8206",
"affiliation": [],
"authenticated-orcid": false,
"family": "Karlebach",
"given": "Guy",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0001-6307-5227",
"affiliation": [],
"authenticated-orcid": false,
"family": "Deer",
"given": "Rachel",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-9353-5498",
"affiliation": [],
"authenticated-orcid": false,
"family": "McMurry",
"given": "Julie A.",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0001-9114-8737",
"affiliation": [],
"authenticated-orcid": false,
"family": "Haendel",
"given": "Melissa A.",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0001-5437-2545",
"affiliation": [],
"authenticated-orcid": false,
"family": "Chute",
"given": "Christopher G.",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-6840-9756",
"affiliation": [],
"authenticated-orcid": false,
"family": "Pfaff",
"given": "Emily",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-2723-5902",
"affiliation": [],
"authenticated-orcid": false,
"family": "Moffitt",
"given": "Richard",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-9420-5028",
"affiliation": [],
"authenticated-orcid": false,
"family": "Spratt",
"given": "Heidi",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-3485-0006",
"affiliation": [],
"authenticated-orcid": false,
"family": "Singh",
"given": "Jasvinder",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-6601-2165",
"affiliation": [],
"authenticated-orcid": false,
"family": "Mungall",
"given": "Christopher J.",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-0692-412X",
"affiliation": [],
"authenticated-orcid": false,
"family": "Williams",
"given": "Andrew E.",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-0736-9199",
"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": "https://syndication.highwire.org/content/doi/10.1101/2021.04.13.21255438",
"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]. [cited 2021 Nov 15]. Available from: https://coronavirus.jhu.edu/map.html"
},
{
"DOI": "10.1016/j.diagmicrobio.2020.115094",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.2"
},
{
"DOI": "10.1016/j.ebiom.2021.103722",
"article-title": "Characterizing Long COVID: Deep Phenotype of a Complex Condition",
"doi-asserted-by": "crossref",
"first-page": "103722",
"journal-title": "EBioMedicine",
"key": "2021122406050511000_2021.04.13.21255438v2.3",
"volume": "74",
"year": "2021"
},
{
"DOI": "10.1136/bmj.329.7456.15",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.4"
},
{
"DOI": "10.1093/infdis/162.6.1277",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.5"
},
{
"DOI": "10.1016/j.cellimm.2009.03.007",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.6"
},
{
"DOI": "10.1136/bmj.m1614",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.7"
},
{
"DOI": "10.1016/j.therap.2020.05.003",
"article-title": "French Society of Pharmacology, Therapeutics (SFPT). Non-steroidal anti-inflammatory drugs, pharmacology, and COVID-19 infection",
"doi-asserted-by": "crossref",
"first-page": "355",
"journal-title": "Therapie",
"key": "2021122406050511000_2021.04.13.21255438v2.8",
"volume": "75",
"year": "2020"
},
{
"DOI": "10.1378/chest.09-3102",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.9"
},
{
"DOI": "10.1111/bcp.14514",
"article-title": "The COVID-19 ibuprofen controversy: A systematic review of NSAIDs in adult acute lower respiratory tract infections",
"doi-asserted-by": "crossref",
"first-page": "776",
"journal-title": "Br J Clin Pharmacol",
"key": "2021122406050511000_2021.04.13.21255438v2.10",
"volume": "87",
"year": "2021"
},
{
"DOI": "10.1001/jamanetworkopen.2020.13880",
"article-title": "Association of Nonsteroidal Anti-inflammatory Drug Use and Adverse Outcomes Among Patients Hospitalized With Influenza",
"doi-asserted-by": "crossref",
"first-page": "e2013880",
"journal-title": "JAMA Netw Open",
"key": "2021122406050511000_2021.04.13.21255438v2.11",
"volume": "3",
"year": "2020"
},
{
"DOI": "10.1128/JVI.00014-21",
"doi-asserted-by": "crossref",
"key": "2021122406050511000_2021.04.13.21255438v2.12",
"unstructured": "Chen Jennifer S. , Alfajaro Mia Madel , Chow Ryan D. , Wei Jin , Filler Renata B. , Eisenbarth Stephanie C. , et al. Nonsteroidal Anti-inflammatory Drugs Dampen the Cytokine and Antibody Response to SARS-CoV-2 Infection. J Virol. American Society for Microbiology; 95:e00014–21."
},
{
"DOI": "10.1056/NEJMra2026131",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.13"
},
{
"DOI": "10.1136/bmj.m1086",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.14"
},
{
"DOI": "10.3390/jcm9061959",
"doi-asserted-by": "crossref",
"key": "2021122406050511000_2021.04.13.21255438v2.15",
"unstructured": "Choi MH , Ahn H , Ryu HS , Kim B-J , Jang J , Jung M , et al. Clinical Characteristics and Disease Progression in Early-Stage COVID-19 Patients in South Korea. J Clin Med Res [Internet]. 2020;9. Available from: http://dx.doi.org/10.3390/jcm9061959"
},
{
"DOI": "10.1136/annrheumdis-2020-eular.3002",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.16"
},
{
"article-title": "Ibuprofen use and clinical outcomes in COVID-19 patients",
"first-page": "1259",
"journal-title": "Clin Microbiol Infect",
"key": "2021122406050511000_2021.04.13.21255438v2.17",
"volume": "26",
"year": "2020"
},
{
"DOI": "10.3390/jcm9082586",
"doi-asserted-by": "crossref",
"key": "2021122406050511000_2021.04.13.21255438v2.18",
"unstructured": "Bruce E , Barlow-Pay F , Short R , Vilches-Moraga A , Price A , McGovern A , et al. Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19. J Clin Med Res [Internet]. 2020;9. Available from: http://dx.doi.org/10.3390/jcm9082586"
},
{
"DOI": "10.1371/journal.pmed.1003308",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.19"
},
{
"DOI": "10.1111/cts.12904",
"article-title": "Association Between Prescribed Ibuprofen and Severe COVID-19 Infection: A Nationwide Register-Based Cohort Study",
"doi-asserted-by": "crossref",
"first-page": "1103",
"journal-title": "Clin Transl Sci",
"key": "2021122406050511000_2021.04.13.21255438v2.20",
"volume": "13",
"year": "2020"
},
{
"DOI": "10.1007/s40121-020-00363-w",
"article-title": "Ibuprofen and NSAID Use in COVID-19 Infected Patients Is Not Associated with Worse Outcomes: A Prospective Cohort Study",
"doi-asserted-by": "crossref",
"first-page": "253",
"journal-title": "Infect Dis Ther",
"key": "2021122406050511000_2021.04.13.21255438v2.21",
"volume": "10",
"year": "2021"
},
{
"DOI": "10.1620/tjem.252.73",
"article-title": "Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran",
"doi-asserted-by": "crossref",
"first-page": "73",
"journal-title": "Tohoku J Exp Med",
"key": "2021122406050511000_2021.04.13.21255438v2.22",
"volume": "252",
"year": "2020"
},
{
"DOI": "10.1002/art.41593",
"article-title": "Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19",
"doi-asserted-by": "crossref",
"first-page": "731",
"journal-title": "Arthritis Rheumatol",
"key": "2021122406050511000_2021.04.13.21255438v2.23",
"volume": "73",
"year": "2021"
},
{
"DOI": "10.1007/s10072-020-04541-z",
"article-title": "Neurological diseases as mortality predictive factors for patients with COVID-19: a retrospective cohort study",
"doi-asserted-by": "crossref",
"first-page": "2317",
"journal-title": "Neurol Sci",
"key": "2021122406050511000_2021.04.13.21255438v2.24",
"volume": "41",
"year": "2020"
},
{
"DOI": "10.1111/joim.13119",
"article-title": "Older age and comorbidity are independent mortality predictors in a large cohort of 1305 COVID-19 patients in Michigan, United States",
"doi-asserted-by": "crossref",
"first-page": "469",
"journal-title": "J Intern Med",
"key": "2021122406050511000_2021.04.13.21255438v2.25",
"volume": "288",
"year": "2020"
},
{
"DOI": "10.1177/1358863X211012754",
"article-title": "Effect of aspirin on short-term outcomes in hospitalized patients with COVID-19",
"doi-asserted-by": "crossref",
"first-page": "626",
"journal-title": "Vasc Med",
"key": "2021122406050511000_2021.04.13.21255438v2.26",
"volume": "26",
"year": "2021"
},
{
"DOI": "10.1016/S2665-9913(21)00104-1",
"article-title": "Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study",
"doi-asserted-by": "crossref",
"first-page": "e498",
"journal-title": "Lancet Rheumatol",
"key": "2021122406050511000_2021.04.13.21255438v2.27",
"volume": "3",
"year": "2021"
},
{
"DOI": "10.1136/annrheumdis-2020-219517",
"doi-asserted-by": "crossref",
"key": "2021122406050511000_2021.04.13.21255438v2.28",
"unstructured": "Wong AY , MacKenna B , Morton CE , Schultze A , Walker AJ , Bhaskaran K , et al. Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts. Ann Rheum Dis [Internet]. 2021; Available from: http://dx.doi.org/10.1136/annrheumdis-2020-219517"
},
{
"DOI": "10.1093/jamia/ocaa196",
"article-title": "The National COVID Cohort Collaborative (N3C): Rationale, design, infrastructure, and deployment",
"doi-asserted-by": "crossref",
"first-page": "427",
"journal-title": "J Am Med Inform Assoc",
"key": "2021122406050511000_2021.04.13.21255438v2.29",
"volume": "28",
"year": "2021"
},
{
"DOI": "10.1093/jamia/ocu023",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.30"
},
{
"DOI": "10.1101/2021.01.12.21249511",
"doi-asserted-by": "crossref",
"key": "2021122406050511000_2021.04.13.21255438v2.31",
"unstructured": "Bennett TD , Moffitt RA , Hajagos JG , Amor B , Anand A , Bissell MM , et al. The National COVID Cohort Collaborative: Clinical Characterization and Early Severity Prediction. medRxiv [Internet]. 2021; Available from: http://dx.doi.org/10.1101/2021.01.12.21249511"
},
{
"DOI": "10.1055/s-0040-1721481",
"article-title": "Patient Cohort Identification on Time Series Data Using the OMOP Common Data Model",
"doi-asserted-by": "crossref",
"first-page": "57",
"journal-title": "Appl Clin Inform",
"key": "2021122406050511000_2021.04.13.21255438v2.32",
"volume": "12",
"year": "2021"
},
{
"article-title": "Observational Health Data Sciences and Informatics (OHDSI): Opportunities for Observational Researchers",
"first-page": "574",
"journal-title": "Stud Health Technol Inform",
"key": "2021122406050511000_2021.04.13.21255438v2.33",
"volume": "216",
"year": "2015"
},
{
"DOI": "10.1016/0021-9681(87)90171-8",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.34"
},
{
"DOI": "10.1016/S1473-3099(20)30483-7",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.35"
},
{
"DOI": "10.7326/M16-2607",
"doi-asserted-by": "publisher",
"key": "2021122406050511000_2021.04.13.21255438v2.36"
},
{
"DOI": "10.21037/atm.2016.08.57",
"article-title": "Propensity score method: a non-parametric technique to reduce model dependence",
"doi-asserted-by": "crossref",
"first-page": "7",
"journal-title": "Ann Transl Med",
"key": "2021122406050511000_2021.04.13.21255438v2.37",
"volume": "5",
"year": "2017"
},
{
"DOI": "10.1007/s40264-021-01089-5",
"article-title": "NSAIDs and COVID-19: A Systematic Review and Meta-analysis",
"doi-asserted-by": "crossref",
"first-page": "929",
"journal-title": "Drug Saf",
"key": "2021122406050511000_2021.04.13.21255438v2.38",
"volume": "44",
"year": "2021"
}
],
"reference-count": 38,
"references-count": 38,
"relation": {},
"resource": {
"primary": {
"URL": "http://medrxiv.org/lookup/doi/10.1101/2021.04.13.21255438"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subtitle": [],
"subtype": "preprint",
"title": "NSAID use and clinical outcomes in COVID-19 patients: A 38-center retrospective cohort study",
"type": "posted-content"
}
