Summary of COVID-19 ibuprofen studies

1. Sobhy et al., Early Use of Ibuprofen in Moderate Cases of COVID-19 Might be a Promising Agent to Attenuate the Severity of Disease: A Randomized Controlled Trial

180 patient ibuprofen late treatment RCT: 52% lower ICU admission (p=0.05), 52% lower need for oxygen therapy (p=0.05), and 26% shorter hospitalization (p=0.01).
RCT 180 moderate hospitalized COVID-19 patients in Egypt, showing lower ICU admission and shorter hospitalization with ibuprofen compared with acetaminophen.
Apr 2023, The Open Anesthesia J., https://openanesthesiajournal.com/VOLUME/17/ELOCATOR/e258964582303020/, https://c19p.org/sobhy

2. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments

15,968 patient ibuprofen prophylaxis study: 48% lower mortality (p=0.002).
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3ib

3. Leal et al., Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis

ibuprofen prophylaxis study: 3% fewer cases (p=0.29).
UK Biobank retrospective showing no significant difference in cases with ibuprofen use.
Aug 2021, COVID, https://www.mdpi.com/2673-8112/1/1/18, https://c19p.org/lealib

4. Drake et al., Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study

ibuprofen prophylaxis study: 10% lower mortality (p=0.36).
Prospective study of 78,674 COVID-19 patients, showing no significant difference in mortality with ibuprofen use.
Jul 2021, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991321001041, https://c19p.org/drake

5. Campbell et al., Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen and relationship with mortality among United States Veterans after testing positive for COVID-19

22,125 patient ibuprofen prophylaxis study: no change in mortality (p=0.54).
Retrospective 28,856 COVID-19 patients in the USA, showing no significant difference in mortality for chronic ibuprofen use vs. sporadic NSAID use. Since ibuprofen is available OTC and authors only tracked prescriptions, many patients classified as sporadic users may have been chronic users.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267462, https://c19p.org/campbell2ib

6. Kragholm et al., Association Between Prescribed Ibuprofen and Severe COVID-19 Infection: A Nationwide Register-Based Cohort Study

4,002 patient ibuprofen prophylaxis study: 4% lower progression (p=0.78).
Retrospective 4,002 COVID-19 patients in Denmark, 264 with ibuprofen prescriptions, showing no significant difference for COVID-19 severity.
Oct 2020, Clinical and Translational Science, https://onlinelibrary.wiley.com/doi/10.1111/cts.12904, https://c19p.org/kragholm

7. Reese et al., Cyclooxygenase inhibitor use is associated with increased COVID-19 severity

11,474 patient ibuprofen prophylaxis PSM study: 9% lower mortality (p=0.65) and 303% higher severe cases (p<0.0001).
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.
Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.13.21255438v1, https://c19p.org/reeseib

8. Xie et al., Risk of COVID-19 Diagnosis and Hospitalization in Patients with Osteoarthritis or Back Pain Treated with Ibuprofen Compared to Other NSAIDs or Paracetamol: A Network Cohort Study

1,697,522 patient ibuprofen prophylaxis study: 12% higher hospitalization (p=0.26) and 8% more cases (p=0.25).
PSM retrospective 1,697,522 osteoarthritis or back pain patients in the US, showing no significant differences in COVID-19 cases and hospitalization for ibuprofen vs. other NSAIDs.
Jul 2022, Drugs, https://link.springer.com/article/10.1007/s40265-022-01822-z, https://c19p.org/xieib

9. Wong et al., Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts

1,977,972 patient ibuprofen prophylaxis study: 23% higher mortality (p=0.19).
Retrospective 2,463,707 people in the UK, showing no significant difference in COVID-19 mortality with NSAID use. Current NSAID users were defined as those ever prescribed an NSAID in the 4 months prior to study start, and non-users were those with no record of NSAID prescription in the same time period.
Jan 2021, Annals of the Rheumatic Diseases, https://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2020-219517, https://c19p.org/wong4ib

10. Rinott et al., Ibuprofen use and clinical outcomes in COVID-19 patients

403 patient ibuprofen early treatment study: 21% higher mortality (p=0.73), 12% higher ventilation (p=0.77), and 40% higher ICU admission (p=0.56).
Retrospective 403 COVID-19 cases in Israel, showing no significant difference in outcomes with ibuprofen use. Patients were asked about ibuprofen use starting a week before diagnosis of COVID-19 - treatment time may have been early, late, or prophylactic.
Sep 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20303438, https://c19p.org/rinott

11. Abu Esba et al., Ibuprofen and NSAID Use in COVID-19 Infected Patients Is Not Associated with Worse Outcomes: A Prospective Cohort Study

397 patient ibuprofen early treatment study: 170% higher mortality (p=0.35), 45% higher need for oxygen therapy (p=0.64), 18% higher hospitalization (p=0.64), and 85% higher severe cases (p=0.42).
Prospective study of 503 COVID-19 cases in Saudi Arabia, 40 using ibuprofen during infection, and 357 not using NSAIDs, showing no significant differences in outcomes. Results are subject to confounding by indication.
Nov 2020, Infectious Diseases and Therapy, http://link.springer.com/10.1007/s40121-020-00363-w, https://c19p.org/abuesba

12. Samimagham et al., The Association of Non-Steroidal Anti-Inflammatory Drugs with COVID-19 Severity and Mortality

158 patient ibuprofen prophylaxis study: 100% higher mortality (p=0.001), 428% higher severe cases (p=0.0007), and 13% higher progression (p=0.04).
Retrospective 158 COVID-19 patients in Iran, showing higher risk of mortality with ibuprofen use.
Jul 2020, Archives of Clinical Infectious Diseases, https://brief.land/archcid/articles/106847.html, https://c19p.org/samimagham2

13. Choi et al., Clinical Characteristics and Disease Progression in Early-Stage COVID-19 Patients in South Korea

72 patient ibuprofen prophylaxis PSM study: 240% higher progression (p=0.26).
Retrospective 293 patients in South Korea, showing higher risk of progression with ibuprofen use, without statistical significance.
Jun 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/6/1959, https://c19p.org/choi2

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