May 4 |
Acetaminophen increases COVID-19 risk: real-time meta analysis of 27 studies | |
| Meta analysis shows 24% [9‑40%] higher mortality, and pooled analysis using the most serious outcome reported shows 28% [17‑41%] higher risk. Concerns have been raised over the use of acetaminophen (paracetamol) for .. | ||
May 19 2024 |
et al., Caspian Journal of Internal Medicine, doi:10.22088/cjim.16.2.381 | Management of critically Ill COVID-19 patients: Exploring the potential of morphine and assessing disadvantages of acetaminophen |
| Discussion of the management of critically ill COVID-19 patients, exploring the potential benefits of morphine and disadvantages of acetaminophen. Authors argue that while acetaminophen is commonly used as a first-line treatment for COVID.. | ||
Nov 8 2023 |
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 |
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.. | ||
Jul 31 2023 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
, 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 24 2022 |
et al., Hospital Pharmacy, doi:10.1177/00185787221125721 | How Much has COVID-19 Contributed to Increase the Worldwide Consumption of Paracetamol and Ibuprofen? Evidence From an Infodemiological Analysis |
| Infodemiological analysis showing a significant worldwide increase in Google searches for paracetamol (54%) and ibuprofen (24%) during the COVID-19 pandemic compared to pre-pandemic levels, suggesting dramatically increased consumption. | ||
Sep 13 2022 |
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 |
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 |
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 |
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. | ||
Jun 17 2022 |
et al., Nucleic Acids Research, doi:10.1093/nar/gkac513 | Body temperature variation controls pre-mRNA processing and transcription of antiviral genes and SARS-CoV-2 replication |
| In Vitro and hamster study showing that higher temperature reduces SARS-CoV-2 replication. Authors show a 1.5°C increase in temperature (from 36.5 to 38°C) enhanced the expression of antiviral genes. Elevated temperatures were found to re.. | ||
May 31 2022 |
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 |
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 |
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 |
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 |
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 |
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 31 2021 |
et al., Computational and Structural Biotechnology Journal, doi:10.1016/j.csbj.2020.12.005 | Temperature dependence of the SARS-CoV-2 affinity to human ACE2 determines COVID-19 progression and clinical outcome |
| In Silico and In Vitro study showing decreased SARS-CoV-2 binding affinity to the human ACE2 receptor at higher temperature (40°C vs. 37°C). Molecular dynamics simulations, surface plasmon resonance experiments, and pseudovirus cell entry.. | ||
Dec 2 2021 |
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 |
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. | ||
Jul 31 2021 |
et al., Journal of the Indian Medical Association, 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 |
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 |
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 | 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 20 2021 |
et al., Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1910570 | The in silico mechanism of hVKOR interaction with acetaminophen and its metabolite, as well as N-acetyl cysteine: caution on application in COVID-19 patients |
| In Silico study suggesting increased risk of cerebral hemorrhage with acetaminophen use for COVID-19. Authors show acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI), and to a lesser extent N-acetylcysteine (NAC), bind to hum.. | ||
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 23 2020 |
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 |
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 | 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., Preprints, 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 |
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 |
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.. | ||
References
Pandolfi et al., Paracetamol in the home treatment of early COVID-19 symptoms: A possible foe rather than a friend for elderly patients?, Journal of Medical Virology, doi:10.1002/jmv.27158.
Sestili et al., Paracetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness?, Frontiers in Pharmacology, doi:10.3389/fphar.2020.579944.
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