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Summary of COVID-19 acetaminophen studies

Studies   Meta Analysis   Hide extended summaries

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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, MDPI AG, https://www.preprints.org/manuscript/202005.0016/v1, https://c19p.org/blanc2

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. Indian Med. Assoc., https://sapiensfoundation.org/wp-content/uploads/2021/08/Use-of-Indomethacin-in-Covid-19-patients-JIMA-2021.pdf, https://c19p.org/ravichandran2ace

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

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

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

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
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.
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