Concerns have been raised over potential harm with the use of NSAIDs for COVID-19 due to the suppression of beneficial immune and inflammatory responses during early infection, and delaying further care. There are currently no early treatment studies for indomethacin. Early treatment results for NSAID ibuprofen suggest higher risk. Indomethacin may be beneficial for cough1, which may not respond to other treatments.
May 4 |
Indomethacin for COVID-19: real-time meta analysis of 4 studies | |
| Significantly lower risk is seen for recovery. 2 studies (both from the same team) show significant benefit. Meta analysis using the most serious outcome reported shows 74% [-20‑94%] lower risk, without reaching statistical sig.. | ||
Dec 8 2024 |
et al., medRxiv, doi:10.1101/2024.12.07.24318645 | Effect of background therapy with Non-steroidal anti-inflammatory drugs (NSAIDs) and other anti-inflammatory agents on COVID-19 outcomes |
| Retrospective 485,779 osteoarthritis patients in the US showing lower mortality with non-aspirin NSAIDs and celecoxib, and higher mortality with aspirin. Aspirin was associated with higher hospitalization in COVID-positive and COVID-negat.. | ||
Nov 15 2024 |
et al., Journal of Chemical Research, doi:10.1177/17475198241298547 | Discovery of potential FDA-approved SARS-CoV-2 Papain-like protease inhibitors: A multi-phase in silico approach |
| In Silico study showing potential inhibition of SARS-CoV-2 papain-like protease (PLpro) by 7 FDA-approved drugs including indomethacin. Authors screened 3,009 drugs and identified indomethacin, vismodegib, celecoxib, ketoprofen, naphazoli.. | ||
Sep 30 2024 |
et al., Journal of Virus Eradication, doi:10.1016/j.jve.2024.100387 | Indomethacin inhibits human seasonal coronaviruses at late stages of viral replication in lung cells: Impact on virus-induced COX-2 expression |
| In Vitro study showing that indomethacin inhibits the replication of human seasonal coronaviruses HCoV-229E (alpha-coronavirus) and HCoV-OC43 (beta-coronavirus) in lung-derived MRC-5 cells. Indomethacin acts at late stages of the viral li.. | ||
Apr 16 2024 |
et al., ScienceOpen, doi:10.58647/DRUGARXIV.PR000010.v1 | Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for COVID-19 disease phases |
| In Silico study identifying potential drugs beneficial for COVID-19 by integrating transcriptomics, proteomics, metabolomics, lipidomics, and drug data. Authors explore interactions between drugs, molecular features, and disease severity... | ||
Feb 2 2024 |
et al., Heliyon, doi:10.1016/j.heliyon.2024.e25734 | Evaluating NSAIDs in SARS-CoV-2: Immunomodulatory mechanisms and future therapeutic strategies |
| Review of NSAIDs and their complex immunomodulatory roles in SARS-CoV-2 infection. Authors discuss the mechanisms by which NSAIDs impact viral replication, immune responses, and inflammation. They note NSAIDs can reduce neutrophil recruit.. | ||
Jan 3 2024 |
et al., BMJ Open, doi:10.1136/bmjopen-2023-077365 | NSAID prescribing and adverse outcomes in common infections: a population-based cohort study |
| 219% higher combined mortality/hospitalization (p<0.0001). Retrospective 142,925 outpatients in the UK showing significantly higher risk of hospitalization or death with prescription of NSAIDs for respiratory tract infections (RTI) or urinary tract infections (UTI). Practice-level analysis also f.. | ||
Oct 18 2023 |
et al., Journal of Infection, doi:10.1016/j.jinf.2023.10.009 | Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract |
| Blood and nasal epithelial transcriptomic analysis suggesting potential benefits of several treatments including: Vitamin E: transcriptomic analysis revealed that the AIPL1 module, which contains genes connected to vitamin E (α-tocopherol.. | ||
Aug 15 2023 |
et al., iScience, doi:10.1016/j.isci.2023.107631 | Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response |
| In Vitro analysis of indomethacin for multiple human coronaviruses including SARS-CoV-2. Indomethacin exhibited antiviral activity against SARS-CoV-2 infection in human cell lines and lung airway organoid models. Treatment with indomethac.. | ||
Mar 31 2023 |
et al., Master's Dissertation | Analysis of the effects of indomethacin on SARS-CoV-2 infection and the inflammatory response associated with the purinergic system |
| Vero E6 and Calu-3 In Vitro study showing that indomethacin protects against SARS-CoV-2-induced cytopathic effects and suppresses ATP-associated inflammatory responses. | ||
Jun 30 2022 |
et al., Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2022.105788 | In-silico screening and in-vitro assay show the antiviral effect of Indomethacin against SARS-CoV-2 |
| In Silico study predicting indomethacin and vitamin A can bind critical host and viral proteins for SARS-CoV-2 interaction, and may be able to compensate for gene expressions changes related to SARS-CoV-2. | ||
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.. | ||
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 |
| 30% improved recovery (p=0.002), 98% lower progression (p<0.0001), and 17% improved viral clearance (p=0.19). RCT with 103 indomethacin and 107 paracetamol patients, showing lower progression and improved recovery with indomethacin. Notably, improvements include faster resolution of cough. [Alkotaji] previously hypothesised the benefit of indomet.. | ||
Jan 13 2022 |
et al., Immunopathologia Persa, doi:10.34172/ipp.2022.xx | Efficacy of oral indomethacin in the treatment of COVID-19 infection; a randomized clinical trial |
| 66% lower ventilation (p=1) and 40% slower recovery (p=0.52). Very small RCT with 22 indomethacin and 23 control patients, showing no significant difference in outcomes. All patients were treated with HCQ. | ||
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 8 2021 |
et al., Medical Science Monitor, doi:10.12659/MSM.935379 | Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis of Early COVID-19 and Treated at Home Within 3 Days or After 3 Days of Symptom Onset with Prescribed and Non-Prescribed Treatments Between November 2020 and August 2021 |
| Retrospective 158 COVID-19 patients in Italy treated with hesperidin, quercetin, indomethacin, aspirin, omeprazole, azithromycin, LMWH, and betamethasone (treatment specific for each patient), showing significantly lower hospitalization a.. | ||
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 |
| 96% lower need for oxygen therapy (p<0.0001) and 43% faster recovery (p<0.0001). PSM retrospective 72 indomethacin and 72 paracetamol patients in India, showing lower progression and improved recovery with indomethacin. | ||
Apr 22 2021 |
et al., Current Pharmacology Reports, doi:10.1007/s40495-021-00257-6 | Indomethacin: Can It Counteract Bradykinin Effects in COVID-19 Patients? |
| Hypothesis that indomethacin will be beneficial for COVID-19 induced dry cough, via inhibition of the cyclooxygenase enzyme and reducing the level of inflammatory mediator bradykinin. | ||
Dec 4 2020 |
et al., Science, doi:10.1126/science.abe9403 | Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms |
| 67% lower hospitalization (p=0.34) and 57% lower progression (p=0.21). Analysis of interactions between viral and human proteins for SARS-CoV-2, SARS-CoV-1, and MERS-CoV and genetic screening to identify host factors that enhance or inhibit viral infection. Authors predict indomethacin will have antiviral ac.. | ||
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.. | ||
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
Alkotaji et al., Indomethacin: Can It Counteract Bradykinin Effects in COVID-19 Patients?, Current Pharmacology Reports, doi:10.1007/s40495-021-00257-6.
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. IMA 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.