TitleNSAID use and clinical outcomes in COVID-19 patients: a 38-center retrospective cohort study.
Publication TypeJournal Article
Year of Publication2022
AuthorsReese, JT, Coleman, B, Chan, LE, Blau, H, Callahan, TJ, Cappelletti, L, Fontana, T, Bradwell, KR, Harris, NL, Casiraghi, E, Valentini, G, Karlebach, G, Deer, R, McMurry, JA, Haendel, MA, Chute, CG, Pfaff, E, Moffitt, R, Spratt, H, Singh, JA, Mungall, CJ, Williams, AE, Robinson, PN
JournalVirol J
Volume19
Issue1
Pagination84
Date Published05/2022
ISSN1743-422X
KeywordsAcute Kidney Injury, Anti-Inflammatory Agents, Non-Steroidal, Cohort Studies, COVID-19, COVID-19 Testing, Humans, Pandemics, Retrospective Studies
Abstract

BACKGROUND: 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.

METHODS: 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 19,746 COVID-19 inpatients was constructed by matching cases (treated with NSAIDs at the time of admission) and 19,746 controls (not treated) from 857,061 patients with COVID-19 available for analysis. 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.

RESULTS: 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.

CONCLUSIONS: 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 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.

DOI10.1186/s12985-022-01813-2
Alternate JournalVirol J
PubMed ID35570298
PubMed Central IDPMC9107579
Grant ListUL1 TR003096 / TR / NCATS NIH HHS / United States
U54 GM104938 / GM / NIGMS NIH HHS / United States
UL1 TR002649 / TR / NCATS NIH HHS / United States
UL1 TR002537 / TR / NCATS NIH HHS / United States
UL1 TR001422 / TR / NCATS NIH HHS / United States
U54 GM104942 / GM / NIGMS NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
UL1 TR002240 / TR / NCATS NIH HHS / United States
UL1 TR002243 / TR / NCATS NIH HHS / United States
NIH UL1TR001439 / NH / NIH HHS / United States
NCATS U24 TR002306 / TR / NCATS NIH HHS / United States
UL1 TR002494 / TR / NCATS NIH HHS / United States
2P30AG024832-16 / / Institute for Translational Sciences, University of Texas Medical Branch /
UL1 TR002736 / TR / NCATS NIH HHS / United States
U54 GM115516 / GM / NIGMS NIH HHS / United States
UL1 TR002369 / TR / NCATS NIH HHS / United States
UL1 TR002001 / TR / NCATS NIH HHS / United States
UL1 TR002538 / TR / NCATS NIH HHS / United States
U54 GM115458 / GM / NIGMS NIH HHS / United States
UL1 TR002535 / TR / NCATS NIH HHS / United States
U24 TR002306 / NH / NIH HHS / United States
UL1 TR001453 / TR / NCATS NIH HHS / United States
UL1 TR002489 / TR / NCATS NIH HHS / United States
U54 GM104940 / GM / NIGMS NIH HHS / United States
UL1 TR003107 / TR / NCATS NIH HHS / United States
UL1 TR003015 / TR / NCATS NIH HHS / United States
UL1 TR002733 / TR / NCATS NIH HHS / United States
U24 TR002306 / TR / NCATS NIH HHS / United States
UL1 TR001876 / TR / NCATS NIH HHS / United States
UL1 TR002003 / TR / NCATS NIH HHS / United States
U54 GM104941 / GM / NIGMS NIH HHS / United States
UL1 TR002553 / TR / NCATS NIH HHS / United States
UL1 TR002389 / TR / NCATS NIH HHS / United States
UL1 TR002014 / TR / NCATS NIH HHS / United States
UL1 TR002319 / TR / NCATS NIH HHS / United States
UL1 TR001855 / TR / NCATS NIH HHS / United States
UL1 TR001425 / TR / NCATS NIH HHS / United States
UL1 TR002373 / TR / NCATS NIH HHS / United States
P30 AG024832 / AG / NIA NIH HHS / United States
UL1 TR001439 / TR / NCATS NIH HHS / United States
UL1 TR001998 / TR / NCATS NIH HHS / United States
UL1 TR001873 / TR / NCATS NIH HHS / United States
UL1 TR001450 / TR / NCATS NIH HHS / United States
U54 GM115428 / GM / NIGMS NIH HHS / United States
UL1 TR002345 / TR / NCATS NIH HHS / United States
UL1 TR002377 / TR / NCATS NIH HHS / United States
UL1 TR002544 / TR / NCATS NIH HHS / United States
UL1 TR003098 / TR / NCATS NIH HHS / United States