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Acetaminophen for COVID-19
28 studies from 297 scientists
543,459 patients in 13 countries
28% higher risk in 28 studies CI 17-41%
24% higher mortality in 14 studies CI 9-40%
COVID-19 Acetaminophen studies. Apr 2024. c19early.org
0 0.5 1 1.5+ All studies -28% With exclusions -26% Mortality -24% Hospitalization -31% Recovery -62% Cases -19% RCTs -50% Symptomatic -29% Prophylaxis -21% Early -22% Late -51% Favorsacetaminophen Favorscontrol
Concerns have been raised over the use of acetaminophen (paracetamol) for COVID-19 Pandolfi, Sestili. Studies show significantly increased risk. Acetaminophen has been officially adopted in 46 countries. Submit updates/corrections.
Apr 22
Covid Analysis Acetaminophen for COVID-19: real-time meta analysis of 28 studies
Meta analysis shows 24% [9‑40%] higher mortality, and pooled analysis using the most serious outcome reported shows 28% [17‑41%] higher risk. 1 RCT with 600 patients has not reported results (8 months late) Marcy. Co..
Nov 8
2023
Rahman et al., Molecular Mechanism Research, 1:1 Clinical & Demographical Status of Hospitalized and Non-Hospitalized Covid-19 Cases: A Multicenter Hospital Based Study in Bangladesh
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 g..
Oct 16
2023
Chen et al., Frontiers in Medicine, doi:10.3389/fmed.2023.1227883 Distinct temporal trajectories and risk factors for Post-acute sequelae of SARS-CoV-2 infection
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 (statistica..
Aug 1
2023
Marcy et al., NCT04920838 Early Treatment of Vulnerable Individuals With Non-Severe SARS-CoV-2 Infection: A Multi-Arm Multi-Stage Randomized Trial (MAMS) to Evaluate the Effectiveness of Several Specific Treatments in Reducing the Risk of Clinical Worsening or Death in Sub-Saharan Africa (COVERAGE-Africa)
Estimated 600 patient acetaminophen early treatment RCT with results not reported over 8 months after estimated completion.
Jul 31
2023
Shakibfar et al., iScience, doi:10.1016/j.isci.2023.107027 AI-based disease risk score for community-acquired pneumonia hospitalization
Pre-COVID model of community-acquired pneumonia (CAP) identifying acetaminophen as one of the top 10 predictors for hospitalization. Authors claim that acetaminophen was not a biologically plausible predictor of CAP, hypothesizing that ac..
Jun 18
2023
Dzieciolowska et al., Clinical Infectious Diseases, doi:10.1093/cid/ciad535 (date from preprint) Timing and Predictors of Loss of Infectivity Among Healthcare Workers With Mild Primary and Recurrent Coronavirus Disease 2019 (COVID-19): A Prospective Observational Cohort Study
383% worse viral clearance (p=0.02). Prospective study of 121 healthcare workers with COVID-19, showing higher risk of viral infectivity with antipyretic use. The antipyretic medications are not specified. Day 5 results exclude the fever group, while the day 7 and day 10 res..
Jun 14
2023
Orellana-Manzano et al., Frontiers in Pharmacology, doi:10.3389/fphar.2023.1197973 A report on SARS-CoV-2 first wave in Ecuador: drug consumption dynamics
Retrospective 10,175 people PCR tested in Ecuador, showing lower risk of PCR+ with multivitamin use and suggesting higher risk with acetaminophen use. The study analyzed drug consumption for COVID-19 symptoms during the 14 days before the..
Apr 28
2023
Ritsinger 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
2023
Sobhy 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
2023
Stufano 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
2023
Chew 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
2023
Kim 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
2023
D’Alessandro 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
2022
Baldia 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
2022
Lorman et al., medRxiv, doi:10.1101/2022.12.22.22283791 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
2022
Sharif 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
2022
Chirumbolo, 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
2022
Abolhassani 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
2022
Fazio et al., Journal of Pharmacy and Pharmacology Research, 6:2022 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
2022
Lapi 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
2022
Xie et al., Drugs, doi:10.1007/s40265-022-01822-z (date from 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
2022
Leo 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
2022
Campbell 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
2022
Ravichandran 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
2022
Lerner 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
2022
MacFadden 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
2022
Moreno-Martos 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
Pandolfi et al., Basic & Clinical Pharmacology & Toxicology, doi:10.1111/bcpt.13690 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
Manjani 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
Marín Dueñas 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
Leal 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.
Jul 31
2021
Ravichandran et al., J. Indian Med. Assoc., 119:7 Use of indomethacin in COVID-19 patients: experience from two medical centres
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.
Jun 25
2021
Pandolfi et al., Journal of Medical Virology, doi:10.1002/jmv.27158 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
Oh 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
Chandan 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
Reese et al., medRxiv, doi:10.1101/2021.04.13.21255438 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
Gálvez-Barrón 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
Park 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 23
2020
Wrotek et al., Evolution, Medicine, and Public Health, doi:10.1093/emph/eoaa044 Let fever do its job
Review of fever focusing on COVID-19. Authors note that fever is a key component of the acute phase response to infection. Fever enhances immune cell performance, induces cellular stress on pathogens, and acts synergistically with other s..
Nov 17
2020
Kolin 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
Sestili et al., Frontiers in Pharmacology, doi:10.3389/fphar.2020.579944 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
Rinott 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
Jeong 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
Blanc et al., MDPI AG, doi:10.20944/preprints202005.0016.v1 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.
Dec 1
1990
Graham et al., Journal of Infectious Diseases, doi:10.1093/infdis/162.6.1277 Adverse Effects of Aspirin, Acetaminophen, and Ibuprofen on Immune Function, Viral Shedding, and Clinical Status in Rhinovirus-Infected Volunteers
RCT examining the effects of aspirin, acetaminophen, and ibuprofen on immune function, virus shedding, and clinical symptoms in 60 healthy volunteers experimentally infected with rhinovirus type 2. The study found that aspirin and acetami..
Apr 30
1988
Downing et al., Journal of Interferon Research, doi:10.1089/jir.1988.8.143 Hyperthermia in Humans Enhances Interferon-γ Synthesis and Alters the Peripheral Lymphocyte Population
Analysis of induced hyperthermia (high body temperature) showing 10 times greater interferon gamma (IFN-γ) production and increased natural killer cells. This response was observed at a core body temperature of ~39°C, highlighting its pot..
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