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Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19

DiNicolantonio et al., Open Heart, doi:10.1136/openhrt-2020-001350

Sep 2020

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Ivermectin for COVID-19

4th treatment shown to reduce risk in August 2020

^*, now known with p < 0.00000000001 from 102 studies, recognized in 22 countries.

Lower risk for mortality, ventilation, ICU admission, hospitalization, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,000+ studies for 60+ treatments. c19ivm.org

Review suggesting that ivermectin may be useful for late stage COVID-19. Authors note that ivermectin, in doses at or modestly above the standard clinical dose, may have important clinical potential for managing disorders associated with life-threatening respiratory distress and cytokine storm, such as advanced COVID-19.

Reviews covering ivermectin for COVID-19 include Adegboro, Al-kuraishy, Babalola, Behl, Bray, DiNicolantonio, DiNicolantonio (B), Elkholy, Fordham, Formiga, Heidary, Jagiasi, Jans, Jans (B), Kory, Kory (B), Kory (C), Kory (D), Kow, Lind, Liu, Loo, Low, Santin, Scheim, Schwartz, Semiz, Turkia, Turkia (B), Turkia (C), Vora, Wang, Wehbe, Yagisawa, Yagisawa (B), Yemeke, Zaidi.

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1. Adegboro et al., A review of the anti-viral effects of ivermectin, African Journal of Clinical and Experimental Microbiology, doi:10.4314/ajcem.v22i3.2.ajol.info, doi.org.

2. Al-kuraishy et al., Central effects of Ivermectin in alleviation of Covid-19-induced dysautonomia, Current Drug Targets, doi:10.2174/1389450123666220810102406.eurekaselect.com, doi.org.

3. Babalola et al., The Place of Ivermectin in the Management of Covid-19: State of the Evidence, Medical Research Archives, doi:10.18103/mra.v11i4.3778.esmed.org, doi.org.

4. Behl et al., CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target, Science of The Total Environment, doi:10.1016/j.scitotenv.2021.152072.sciencedirect.com, doi.org.

5. Bray et al., Ivermectin and COVID-19: A report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors' responses, Antiviral Res., doi:10.1016/j.antiviral.2020.104805.nih.gov, doi.org.

6. DiNicolantonio et al., Anti-inflammatory activity of ivermectin in late-stage COVID-19 may reflect activation of systemic glycine receptors, Open Heart, doi:10.1136/openhrt-2021-001655.bmj.com, doi.org.

7. DiNicolantonio (B) et al., Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19, Open Heart, doi:10.1136/openhrt-2020-001350.bmj.com, doi.org.

8. Elkholy et al., Ivermectin: A Closer Look at a Potential Remedy, Cureus, doi:10.7759/cureus.10378.cureus.com, doi.org.

9. Fordham et al., The uses and abuses of systematic reviews, OSF Preprints, doi:10.31219/osf.io/mp4f2.osf.io, doi.org.

10. Formiga et al., Ivermectin: an award-winning drug with expected antiviral activity against COVID-19, J. Control Release, doi:10.1016/j.jconrel.2020.10.009.nih.gov, doi.org.

11. Heidary et al., Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen, The Journal of Antibiotics, 73, 593–602, doi:10.1038/s41429-020-0336-z.nature.com, doi.org.

12. Jagiasi et al., Variation in therapeutic strategies for the management of severe COVID-19 in India- A nationwide cross-sectional survey, The International Journal of Clinical Practice, doi:10.1111/ijcp.14574.wiley.com, doi.org.

13. Jans et al., The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ?, Biochemical and Biophysical Research Communications, doi:10.1016/j.bbrc.2020.10.042.sciencedirect.com, doi.org.

14. Jans (B) et al., Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?, Cells 2020, 9:9, 2100, doi:10.3390/cells9092100.mdpi.com, doi.org.

15. Kory, P., The Global War on Ivermectin, International Covid Summit III, European Parliament, Brussels, covid19criticalcare.com/wp-content/uploads/2023/05/GLOBAL-WAR-ON-IVERMECTIN-PARLIAMENT.pdf.covid19criticalcare.com.

16. Kory (B), P., The Criminal Censorship of Ivermectin's Efficacy By The High-Impact Medical Journals - Part 1, Pierre Kory’s Medical Musings, pierrekory.substack.com/p/the-criminal-censorship-of-ivermectins.substack.com.

17. Kory (C) et al., Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19, American Journal of Therapeutics, doi:10.1097/MJT.0000000000001377.lww.com, doi.org.

18. Kory (D) et al., Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19, Frontiers in Pharmacology, doi:10.3389/fphar.2021.643369.archive.org, doi.org.

19. Kow et al., Pitfalls in Reporting Sample Size Calculation Across Randomized Controlled Trials Involving Ivermectin for the treatment of COVID-19, American Journal of Therapeutics, doi:10.1097/MJT.0000000000001441.lww.com, doi.org.

20. Lind et al., Increase in Outpatient Ivermectin Dispensing in the US During the COVID-19 Pandemic: A Cross-Sectional Analysis, Journal of General Internal Medicine, doi:10.1007/s11606-021-06948-6.springer.com, doi.org.

21. Liu et al., Crosstalk between neutrophil extracellular traps and immune regulation: insights into pathobiology and therapeutic implications of transfusion-related acute lung injury, Frontiers in Immunology, doi:10.3389/fimmu.2023.1324021.frontiersin.org, doi.org.

22. Loo et al., Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections, Pharmaceutical Research, doi:10.1007/s11095-023-03520-1.springer.com, doi.org.

23. Low et al., Repositioning Ivermectin for Covid-19 treatment: Molecular mechanisms of action against SARS-CoV-2 replication, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, doi:10.1016/j.bbadis.2021.166294.sciencedirect.com, doi.org.

24. Santin et al., Ivermectin: a multifaceted drug of Nobel prize-honored distinction with indicated efficacy against a new global scourge, COVID-19, New Microbes and New Infections, doi:10.1016/j.nmni.2021.100924.sciencedirect.com, doi.org.

25. Scheim et al., Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and Endothelial Cells Govern the Severe Morbidities of COVID-19, International Journal of Molecular Sciences, doi:10.3390/ijms242317039.mdpi.com, doi.org.

26. Schwartz, E., Does ivermectin have a place in the treatment of mild Covid-19?, New Microbes and New Infections, doi:10.1016/j.nmni.2022.100989.sciencedirect.com, doi.org.

27. Semiz, S., SIT1 transporter as a potential novel target in treatment of COVID-19, Biomolecular Concepts, doi:10.1515/bmc-2021-0017.degruyter.com, doi.org.

28. Turkia, M., A Continuation of a Timeline of Ivermectin-Related Events in the COVID-19 Pandemic [June 30, 2021], ResearchGate, doi:10.13140/RG.2.2.16973.36326.researchgate.net, doi.org.

29. Turkia (B), M., A timeline of ivermectin-related events in the COVID-19 pandemic, Research Gate, www.researchgate.net/publication/350610718_A_Timeline_of_Ivermectin-Related_Events_in_the_COVID-19_Pandemic_April_3_2021.researchgate.net.

30. Turkia (C), M., FLCCC Alliance MATH+ ascorbic acid and I-MASK+ ivermectin protocols for COVID-19 — a brief review, ResearchGate, www.researchgate.net/profile/Mika_Turkia/publication/345694745_FLCCC_Alliance_MATH_ascorbic_acid_and_I-MASK_ivermectin_protocols_for_COVID-19_-_A_Brief_Review/links/5fab010f4585150781078260/FLCCC-Alliance-MATH-ascorbic-acid-and-I-MASK-ivermectin-protocols-for-COVID-19-A-Brief-Review.pdf.researchgate.net.

31. Vora et al., White paper on Ivermectin as a potential therapy for COVID-19, Indian Journal of Tuberculosis, doi:10.1016/j.ijtb.2020.07.031.sciencedirect.com, doi.org.

32. Wang et al., Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19, medRxiv, doi:10.1101/2021.06.01.21258147.medrxiv.org, doi.org.

33. Wehbe et al., Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities, Front. Immunol., doi:10.3389/fimmu.2021.663586.frontiersin.org, doi.org.

34. Yagisawa et al., Global trends in clinical trials of ivermectin for COVID-19—Part 2, The Japanese Journal of Antibiotics, doi:10.11553/antibiotics.77.1_45.doi.org, doi.org.

35. Yagisawa (B) et al., Global trends in clinical studies of ivermectin in COVID-19, The Japanese Journal of Antibiotics, 74-1, Mar 2021, jja-contents.wdc-jp.com/pdf/JJA74/74-1-open/74-1_44-95.pdf.wdc-jp.com.

36. Yemeke et al., Impact of the COVID-19 pandemic on the quality of medical products in Zimbabwe: a qualitative study based on key informant interviews with health system stakeholders, BMJ Open, doi:10.1136/bmjopen-2022-068923.bmj.com, doi.org.

37. Zaidi et al., The mechanisms of action of ivermectin against SARS-CoV-2—an extensive review, The Journal of Antibiotics, doi:10.1038/s41429-021-00491-6.nature.com, doi.org.

DiNicolantonio et al., 6 Sep 2020, peer-reviewed, 3 authors.

This Paper Ivermectin All

Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19

Dr James J Dinicolantonio, Jorge Barroso, Mark Mccarty

Open Heart, doi:10.1136/openhrt-2020-001350

Author name Jorge Barroso has been corrected to Jorge Barroso-Aranda.

References

Andersson, Ottestad, Tracey, Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19?, Mol Med, doi:10.1186/s10020-020-00172-4

Caly, Druce, Catton, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res, doi:10.1016/j.antiviral.2020.104787

Capellini, Venditti, Barton, Phylogeny and metabolic scaling in mammals, Ecology, doi:10.1890/09-0817.1

Ci, Li, Yu, Avermectin exerts anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogen-activated protein kinase activation pathway, Fundam Clin Pharmacol, doi:10.1111/j.1472-8206.2009.00684.x

Gorial, Mashhadani, Sayaly, Effectiveness of ivermectin as add-on therapy in COVID-19 management, medRxiv

Rajter, Sm, Fatteh, Vogel, Icon (ivermectin Ni COvid nineteen) study: use of ivermectin is associated with lower mortality in hospitalized patients with COVID19, medRxiv

Schmith, Zhou, Lohmer, The Approved dose of ivermectin alone is not the ideal dose for the treatment of COVID-19, Clin Pharmacol Ther, doi:10.1002/cpt.1889

Ventre, Rozières, Lenief, Topical ivermectin improves allergic skin inflammation, Allergy, doi:10.1111/all.13118

Yan, Ci, Chen, Anti-Inflammatory effects of ivermectin in mouse model of allergic asthma, Inflamm Res, doi:10.1007/s00011-011-0307-8

Zhang, Song, Ci, Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice, Inflamm Res, doi:10.1007/s00011-008-8007-8

Zhang, Song, Xiong, Inhibitory effects of ivermectin on nitric oxide and prostaglandin E2 production in LPS-stimulated RAW 264.7 macrophages, Int Immunopharmacol, doi:10.1016/j.intimp.2008.12.016

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