Summary of COVID-19 acetaminophen studies

acetaminophen prophylaxis study: 7% fewer cases (p=0.004).
UK Biobank retrospective showing lower cases with acetaminophen use.
Aug 2021, COVID, https://www.mdpi.com/2673-8112/1/1/18, https://c19p.org/leal

2. Park et al., Non-steroidal anti-inflammatory agent use may not be associated with mortality of coronavirus disease 19

794 patient acetaminophen prophylaxis PSM study: 25% lower mortality (p=0.46) and 38% lower ventilation (p=0.42).
Retrospective 2,365 patients prescribed acetaminophen and 398 prescribed NSAIDs in South Korea, showing no significant differences.
Mar 2021, Scientific Reports, http://www.nature.com/articles/s41598-021-84539-5, https://c19p.org/park2

3. Baldia et al., The association of prior paracetamol intake with outcome of very old intensive care patients with COVID-19: results from an international prospective multicentre trial

2,646 patient acetaminophen ICU study: 12% lower mortality (p=0.2).
Prospective study of 2,646 ICU patients ≥70 years old, showing no significant difference in mortality with acetaminophen use in the 10 days prior to ICU admission.
Dec 2022, BMC Geriatrics, https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-022-03709-w, https://c19p.org/baldia

4. Oh et al., Musculoskeletal Disorders, Pain Medication, and in-Hospital Mortality among Patients with COVID-19 in South Korea: A Population-Based Cohort Study

7,713 patient acetaminophen prophylaxis study: 2% lower mortality (p=0.97).
Retrospective 7,713 COVID-19 patients in Korea, showing no significant difference in mortality with paracetamol use.
Jun 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/13/6804, https://c19p.org/oh3

5. Gálvez-Barrón et al., COVID-19: Clinical Presentation and Prognostic Factors of Severe Disease and Mortality in the Oldest-Old Population: A Cohort Study

103 patient acetaminophen prophylaxis study: 47% higher mortality (p=0.42) and 23% lower severe cases (p=0.55).
Analysis of 103 elderly hospitalized COVID-19 patients in Spain, showing higher mortality with acetaminophen, without statistical significance.
Apr 2021, Gerontology, https://www.karger.com/Article/FullText/515159, https://c19p.org/galvezbarron

6. 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

1,370,600 patient acetaminophen prophylaxis study: 5% higher hospitalization (p=0.83) and 3% fewer cases (p=0.82).
PSM retrospective 1,370,600 osteoarthritis or back pain patients in the US, showing no significant differences in COVID-19 cases and hospitalization for paracetamol vs. ibuprofen.
Jul 2022, Drugs, https://link.springer.com/article/10.1007/s40265-022-01822-z, https://c19p.org/xie

7. Rahman et al., Clinical & Demographical Status of Hospitalized and Non-Hospitalized Covid-19 Cases: A Multicenter Hospital Based Study in Bangladesh

600 patient acetaminophen early treatment study: 23% higher hospitalization (p=0.11).
Retrospective 416 non-hospitalized and 184 hospitalized COVID-19 patients in Bangladesh, showing higher acetaminophen and lower vitamin C usage for hospitalized patients. Confounding may be significant and baseline details per treatment group are not provided, however fever and symptomatic patients were more common in the non-hospitalized group. Note there is an alignment mismatch in Table 1.
Nov 2023, Molecular Mechanism Research, https://ojs.as-pub.com/index.php/MMR/article/view/133, https://c19p.org/rahman5ace

8. Jeong et al., Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study

acetaminophen early treatment study: 15% worse results (p=0.61).
Retrospective 1,824 hospitalized COVID-19 patients in South Korea, showing higher progression to combined death, ICU, ventilation, or sepsis (4% versus 0%, group sizes not provided) with paracetamol vs. NSAIDs. Treatment time may vary - exposure was defined as 7 days before and including cohort entry in hospitalized COVID-19 patients.
Jul 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/73/11/e4179/5876905, https://c19p.org/jeong

9. Chandan et al., Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19

17,190 patient acetaminophen prophylaxis PSM study: 18% higher mortality (p=0.35) and 27% more cases (p=0.17).
Retrospective 12,457 patients prescribed paracetamol with codeine/dihydrocodeine and 13,202 prescribed NSAIDs, showing no significant differences in cases and mortality. Patients prescribed codeine/dihydrocodeine may have different susceptibility to COVID-19.
Apr 2021, Arthritis & Rheumatology, https://onlinelibrary.wiley.com/doi/10.1002/art.41593, https://c19p.org/chandan

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

134 patient acetaminophen early treatment study: 473% higher mortality (p=0.3) and 534% higher need for oxygen therapy (p=0.06).
Retrospective 89 febrile COVID-19 patients in Israel taking paracetamol and 49 taking ibuprofen, showing higher need for respiratory support with paracetamol. Although not statistically significant, patients in the paracetamol group were older.
Sep 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20303438, https://c19p.org/rinottace

11. Chen et al., Distinct temporal trajectories and risk factors for Post-acute sequelae of SARS-CoV-2 infection

354 patient acetaminophen long COVID study: 32% higher PASC (p=0.07).
Prospective study of 494 COVID-19 patients showing higher risk of PASC with acetaminophen use in unadjusted results, without reaching statistical significance (p=0.07). Higher risk is also seen for dexamethasone and remdesivir (statistically significant for dexamethasone), however confounding by indication may be significant for these treatments, with increased use for more severe patients. While details of treatment timing and dose are not available, the result for acetaminophen can be compared with ibuprofen, with comparable indication for use. Notably there is no increased risk with ibuprofen, suggesting higher risk with acetaminophen, consistent with the higher risk seen in meta analysis.
Oct 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1227883/full, https://c19p.org/chen12

12. Ritsinger et al., History of heart failure and chronic kidney disease and risk of all-cause death after COVID-19 during the first three waves of the pandemic in comparison with influenza outbreaks in Sweden: a registry-based, retrospective, case–control study

44,866 patient acetaminophen prophylaxis study: 21% higher mortality (p<0.0001).
Retrospective 44,866 hospitalized COVID-19 patients in Sweden, showing higher mortality with vitamin D deficiency and with acetaminophen use. The study focuses on cardiorenal disease, finding higher risk of mortality with CRD. Authors also show that COVID-19 mortality was about 1.5x higher when compared with influenza in the first two pandemic waves, but there was no significant difference in the third wave (HR 1.53 [1.45-1.62] and 1.52 [1.44-1.61] in the first two waves and 1.07 [0.99-1.14] in the third).
Apr 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-069037, https://c19p.org/ritsinger

13. Stufano et al., Oxidative Damage and Post-COVID Syndrome: A Cross-Sectional Study in a Cohort of Italian Workers

80 patient acetaminophen late treatment study: 19% higher PASC (p=0.62).
Retrospective 80 mild COVID-19 patients in Italy, showing no significant difference in long COVID with acetaminophen use during infection.
Apr 2023, Int. J. Molecular Sciences, https://www.mdpi.com/1422-0067/24/8/7445, https://c19p.org/stufano

14. Lapi et al., To clarify the safety profile of paracetamol for home-care patients with COVID-19: a real-world cohort study, with nested case–control analysis, in primary care

acetaminophen early treatment study: 15% higher combined mortality/hospitalization (p=0.22).
Retrospective paracetamol use with a primary care database in Italy, showing no significant difference in hospitalization/death for use 0-3 and 4-7 days from diagnosis, and significantly higher risk for use >7 days from diagnosis. Confounding by indication may have a greater effect on late usage.
Jul 2022, Internal and Emergency Medicine, https://link.springer.com/10.1007/s11739-022-03054-1, https://c19p.org/lapi

15. 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

22,385 patient acetaminophen prophylaxis study: 1% higher mortality (p=0.43).
Retrospective 28,856 COVID-19 patients in the USA, showing no significant difference in mortality for chronic acetaminophen use vs. sporadic NSAID use. Since acetaminophen 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/campbell2ace

16. Lerner et al., Mining Electronic Health Records for Drugs Associated With 28-day Mortality in COVID-19: Pharmacopoeia-wide Association Study (PharmWAS)

5,783 patient acetaminophen late treatment study: 27% higher mortality (p=0.1).
Retrospective 5,783 hospitalized patients in France, showing higher mortality with paracetamol use, without statistical significance.
Mar 2022, JMIR Medical Informatics, https://medinform.jmir.org/2022/3/e35190, https://c19p.org/lerner

17. MacFadden et al., Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications

acetaminophen prophylaxis study: 48% more cases (p<0.0001).
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing higher cases with chronic use of acetaminophen.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenace

18. Moreno-Martos et al., Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe

99,890 patient acetaminophen prophylaxis study: 29% higher hospitalization (p<0.0001).
Aanlysis of prescriptions in multiple databases showing higher risk of COVID-19 hospitalization with acetaminophen use for COPD patients. Acetaminophen use was more prevalent in hospitalized patients compared to diagnosed patients (data from tables 1, 5, and S3).
Jan 2022, Wellcome Open Research, https://wellcomeopenresearch.org/articles/7-22/v3, https://c19p.org/morenomartos

19. Kolin et al., Clinical, regional, and genetic characteristics of Covid-19 patients from UK Biobank

397,064 patient acetaminophen prophylaxis study: 23% more cases (p=0.009).
397,064 patient UK Biobank retrospective showing higher risk of COVID-19 with acetaminophen use.
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241264, https://c19p.org/kolin

20. Sharif et al., Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study

503 patient acetaminophen early treatment study: 77% higher mortality (p=0.74).
Retrospective COVID-19 patients in Bangladesh, showing higher mortality with acetaminophen use in unadjusted results.
Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/shariface

21. Abolhassani et al., Genetic and immunological evaluation of children with inborn errors of immunity and severe or critical COVID-19

31 patient acetaminophen late treatment study: 56% higher mortality (p=0.64).
Retrospective 31 hospitalized patients ≤19 with pre-existing inborn errors of immunity, showing no significant difference in mortality with acetaminophen. Only 6 patients were treated with acetaminophen.
Sep 2022, J. Allergy and Clinical Immunology, https://www.sciencedirect.com/science/article/pii/S009167492201185X, https://c19p.org/abolhassani

22. Kim et al., Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Population-Based Cohort Study

324 patient acetaminophen prophylaxis PSM study: 71% higher mortality (p=0.34), 14% higher ventilation (p=1), 40% lower ICU admission (p=0.72), and 9% higher need for oxygen therapy (p=0.87).
PSM retrospective in South Korea, showing no significant differences in outcomes with acetaminophen use vs. NSAID use. Adherence and dosage are unknown.
Feb 2023, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/20/5/3832, https://c19p.org/kim7

23. Blanc et al., Interest of Proton Pump Inhibitors in Reducing the Occurrence of COVID-19: A Case-Control Study

179 patient acetaminophen prophylaxis study: 51% more cases (p=0.19).
Retrospective 179 elderly patients in France, showing higher risk of COVID-19 cases with acetaminophen use, without statistical significance.
May 2020, Preprints, https://www.preprints.org/manuscript/202005.0016/v1, https://c19p.org/blanc2

24. Ravichandran et al., Use of indomethacin in COVID-19 patients: experience from two medical centres

144 patient acetaminophen late treatment PSM study: 2700% higher need for oxygen therapy (p<0.0001) and 75% slower recovery (p<0.0001).
PSM retrospective 72 indomethacin and 72 paracetamol patients in India, showing higher progression and worse recovery with acetaminophen.
Jul 2021, J. the Indian Medical Association, https://sapiensfoundation.org/wp-content/uploads/2021/08/Use-of-Indomethacin-in-Covid-19-patients-JIMA-2021.pdf, https://c19p.org/ravichandran2ace

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

41,652 patient acetaminophen prophylaxis PSM study: 61% higher mortality (p<0.0001) and 816% higher severe cases (p<0.0001).
N3C retrospective 250,533 patients showing significantly higher mortality with acetaminophen use. Note that acetaminophen results were not included in the journal version or v2 of this preprint, which focuses on NSAID analysis.
Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.13.21255438v1, https://c19p.org/reese

26. 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 acetaminophen late treatment RCT: 110% higher ICU admission (p=0.05), 110% higher need for oxygen therapy (p=0.05), and 36% longer hospitalization (p=0.01).
RCT 180 moderate hospitalized COVID-19 patients in Egypt, showing higher ICU admission and longer hospitalization with acetaminophen compared with ibuprofen.
Apr 2023, The Open Anesthesia J., https://openanesthesiajournal.com/VOLUME/17/ELOCATOR/e258964582303020/, https://c19p.org/sobhyace

27. Ravichandran et al., An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients

210 patient acetaminophen late treatment RCT: 43% worse recovery (p=0.002), 3925% higher progression (p<0.0001), and 20% worse viral clearance (p=0.19).
RCT with 107 paracetamol and 103 indomethacin patients, showing higher progression and worse recovery with paracetamol.
Apr 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-10370-1, https://c19p.org/ravichandranace

28. Manjani et al., Effects of acetaminophen on outcomes in patients hospitalized with COVID-19

524 patient acetaminophen late treatment study: 220% higher mortality (p=0.001), 434% higher ventilation (p=0.001), 244% higher progression (p=0.005), and 100% longer hospitalization (p=0.001).
Retrospective 524 hospitalized patients in the USA, showing higher mortality and progression with acetaminophen use.
Oct 2021, Chest, https://www.sciencedirect.com/science/article/pii/S0012369221024430, https://c19p.org/manjani

Submit Corrections or Updates

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

Thanks for your feedback! Please search before submitting papers and note that studies are listed under the date they were first available, which may be the date of an earlier preprint.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0