Acetaminophen COVID-19 studies. Concerns have been raised over the use of acetaminophen for COVID-19 [Pandolfi, Sestili]. Studies to date show increased risk. Data is limited, with RCTs to date comparing with indomethacin/ibuprofen.
Recent:Sobhy Fazio Marín Dueñas Ritsinger Stufano Chew Leo.
Acetaminophen has been officially adopted
in 44 countries.
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May 29 |
(Preprint) (meta analysis) | Acetaminophen for COVID-19: real-time meta analysis of 25 studies |
| Meta analysis using the most serious outcome reported shows 28% [16‑41%] higher risk. • Concerns have been raised over the use of acetaminophen for COVID-19 [Pandolfi, Sestili]. Studies to date show increased risk. Data is li.. | ||
Apr 28 |
et al., BMJ Open, doi:10.1136/bmjopen-2022-069037 | 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 |
| 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 als.. | ||
Apr 19 |
et al., The Open Anesthesia Journal, doi:10.2174/25896458-v17-e230403-2022-26 | 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 |
| 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 18 |
et al., International Journal of Molecular Sciences, doi:10.3390/ijms24087445 | Oxidative Damage and Post-COVID Syndrome: A Cross-Sectional Study in a Cohort of Italian Workers |
| 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. | ||
Mar 16 |
et al., Pathogens, doi:10.3390/pathogens12030473 | Clinical Predictors for Abnormal ALT in Patients Infected with COVID-19—A Retrospective Single Centre Study |
| 186% higher progression [p=0.14]. Retrospective 163 COVID-19 patients in Singapore, showing increased risk of liver injury (abnormal ALT) with acetaminophen in a dose-dependent manner, and with remdesivir, without statistical significance in both cases. | ||
Feb 21 |
et al., International Journal of Environmental Research and Public Health, doi:10.3390/ijerph20053832 | Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Population-Based Cohort 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 13 |
et al., Scientific Reports, doi:10.1038/s41598-023-29519-7 | Contribution of vitamin D3 and thiols status to the outcome of COVID-19 disease in Italian pediatric and adult patients |
| Retrospective 173 patients in Italy showing significantly lower glutathione levels and high prevalence of vitamin D deficiency in COVID-19 patients, and lower levels of glutathione and vitamin D associated with mortality. Acetaminophen (p.. | ||
Dec 27 |
et al., BMC Geriatrics, doi:10.1186/s12877-022-03709-w | The association of prior paracetamol intake with outcome of very old intensive care patients with COVID-19: results from an international prospective multicentre trial |
| 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 26 |
et al., medRxiv, doi:10.1101/2022.12.22.22283791 (Preprint) | A machine learning-based phenotype for long COVID in children: an EHR-based study from the RECOVER program |
| Retrospective 87,398 pediatric patients in the USA, reporting acetaminophen and aspirin associated with PASC, without specific details. Authors note that this could be related to use for MIS-C treatment. | ||
Nov 26 |
et al., Nutrients, doi:10.3390/nu14235029 | Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study |
| 77% higher mortality [p=0.74]. Retrospective COVID-19 patients in Bangladesh, showing higher mortality with acetaminophen use in unadjusted results. | ||
Nov 11 |
, S., Journal of Medical Virology, doi:10.1002/jmv.28301 | The widest use of paracetamol in home therapy might have actually increased the occurrence of severe forms of COVID-19 in Italy, affecting hospitalization and death rates. |
| Analysis of COVID-19 cases in Italy reporting a higher risk of hospitalization in intensive therapy units after the recommendation to use paracetamol. | ||
Sep 13 |
et al., Journal of Allergy and Clinical Immunology, doi:10.1016/j.jaci.2022.09.005 | Genetic and immunological evaluation of children with inborn errors of immunity and severe or critical COVID-19 |
| 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. | ||
Aug 2 |
et al., Journal of Pharmacy and Pharmacology Research, 6:2022 (Review) | The Problem of Home Therapy during COVID-19 Pandemic in Italy: Government Guidelines versus Freedom of Cure? |
| Review of early COVID-19 treatment in Italy discussing the lack of effective treatment and the use of paracetamol as recommended by authorities, and alternative evidence-based approaches adopted by physicians. | ||
Jul 30 |
et al., Internal and Emergency Medicine, doi:10.1007/s11739-022-03054-1 | 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 |
| 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. Confoun.. | ||
Jul 13 |
et al., Drugs, doi:10.1007/s40265-022-01822-z (date from earlier preprint) | 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 |
| 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. | ||
May 31 |
et al., Digestive and Liver Disease, doi:10.1016/j.dld.2021.12.014 | Hepatocellular liver injury in hospitalized patients affected by COVID-19: Presence of different risk factors at different time points |
| 167% higher progression [p=0.004]. Retrospective 292 patients in Switzerland showing liver damage associated with acetaminophen treatment and remdesivir treatment. | ||
May 5 |
et al., PLOS ONE, doi:10.1371/journal.pone.0267462 | 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 |
| 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 pati.. | ||
Apr 19 |
et al., Scientific Reports, doi:10.1038/s41598-022-10370-1 | An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients |
| 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. | ||
Mar 30 |
et al., JMIR Medical Informatics, doi:10.2196/35190 | Mining Electronic Health Records for Drugs Associated With 28-day Mortality in COVID-19: Pharmacopoeia-wide Association Study (PharmWAS) |
| 27% higher mortality [p=0.1]. Retrospective 5,783 hospitalized patients in France, showing higher mortality with paracetamol use, without statistical significance. | ||
Mar 29 |
et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac156 | Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications |
| 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. | ||
Jan 24 |
et al., Wellcome Open Research, doi:10.12688/wellcomeopenres.17403.3 | Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe |
| 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 f.. | ||
Dec 2 2021 |
et al., Basic & Clinical Pharmacology & Toxicology, doi:10.1111/bcpt.13690 (Review) | Home pharmacological therapy in early COVID-19 to prevent hospitalization and reduce mortality: Time for a suitable proposal |
| Proposal for early treatment of COVID-19, including a review of potential concerns for treatment with acetaminophen and a recommendation against using acetaminophen. | ||
Oct 31 2021 |
et al., Chest, doi:10.1016/j.chest.2021.07.992 | Effects of acetaminophen on outcomes in patients hospitalized with COVID-19 |
| 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. | ||
Sep 30 2021 |
et al., Annals of Hepatology, doi:10.1016/j.aohep.2021.100391 | Alteration in liver function tests among patients hospitalized for COVID-19: a multicentric study in Peru |
| 41% higher progression [p=0.05]. Retrospective 1,100 COVID-19 patients in Peru, showing higher risk of liver injury with paracetamol use. | ||
Aug 16 2021 |
et al., COVID, doi:10.3390/covid1010018 | Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis |
| 7% fewer cases [p=0.004]. UK Biobank retrospective showing lower cases with acetaminophen use. | ||
Jun 25 2021 |
et al., Journal of Medical Virology, doi:10.1002/jmv.27158 (Review) | Paracetamol in the home treatment of early COVID-19 symptoms: A possible foe rather than a friend for elderly patients? |
| Review of potential concerns for treatment of COVID-19 with acetaminophen. | ||
Jun 24 2021 |
et al., International Journal of Environmental Research and Public Health, doi:10.3390/ijerph18136804 | Musculoskeletal Disorders, Pain Medication, and in-Hospital Mortality among Patients with COVID-19 in South Korea: A Population-Based Cohort Study |
| 2% lower mortality [p=0.97]. Retrospective 7,713 COVID-19 patients in Korea, showing no significant difference in mortality with paracetamol use. | ||
Apr 29 2021 |
et al., Arthritis & Rheumatology, doi:10.1002/art.41593 | Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19 |
| 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 suscep.. | ||
Apr 20 2021 |
et al., medRxiv, doi:10.1101/2021.04.13.21255438 (Preprint) | Cyclooxygenase inhibitor use is associated with increased COVID-19 severity |
| 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 14 2021 |
et al., Gerontology, doi:10.1159/000515159 | COVID-19: Clinical Presentation and Prognostic Factors of Severe Disease and Mortality in the Oldest-Old Population: A Cohort 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. | ||
Mar 3 2021 |
et al., Scientific Reports, doi:10.1038/s41598-021-84539-5 | Non-steroidal anti-inflammatory agent use may not be associated with mortality of coronavirus disease 19 |
| 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. | ||
Nov 17 2020 |
et al., PLOS ONE, doi:10.1371/journal.pone.0241264 | Clinical, regional, and genetic characteristics of Covid-19 patients from UK Biobank |
| 23% more cases [p=0.009]. 397,064 patient UK Biobank retrospective showing higher risk of COVID-19 with acetaminophen use. | ||
Oct 7 2020 |
et al., Frontiers in Pharmacology, doi:10.3389/fphar.2020.579944 (Review) | Paracetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness? |
| Discussion of the potential negative effects of acetaminophen for COVID-19 based on promotion of glutathione depletion, especially in population groups at higher risk. | ||
Sep 30 2020 |
et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.06.003 | Ibuprofen use and clinical outcomes in COVID-19 patients |
| 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 .. | ||
Jul 27 2020 |
et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa1056 | Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study |
| 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 - e.. | ||
May 2 2020 |
et al., MDPI AG, doi:10.20944/preprints202005.0016.v1 (Preprint) | Interest of Proton Pump Inhibitors in Reducing the Occurrence of COVID-19: A Case-Control 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. | ||
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