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The Remdesivir Anthology Series Archives
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The Anthology Series Archives

The Remdesivir Anthology Series Archives

A Collection of posts on Remdesivir and Citations

Modern Discontent
Mar 1
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This post was copied and pasted over from Modern Discontent. If you are interested in Anthology Series posts as they come in or are interested in smaller posts along the way please consider subscribing over there as that is the main Substack. Also, paid-only content will only be available through becoming a paid member on Modern Discontent.

This post is comprised of my Remdesivir newsletters where I examined some of the available information surrounding Remdesivir including its possible toxicities.


Part I: Introduction, Brief History, and Mechanism of Action

This is the first post in the series and sets up the rest of the newsletters down the line. A twitter post lead to a testament by a COVID nurse discussing the ineffectiveness of treatments and the dangers of Remdesivir, leading to the search for evidence of possible toxicity.

Modern Discontent
Remdesivir: COVID's Standard of Care that May be Causing more Harm than Good (REVIEW)
Last week a Twitter post began circulating in which a nurse talked about standard of care drugs doing nothing to help with COVID. In particular she mentions Remdesivir. Not only does she talk about it not being effective, but she mentioned several instances of organ failure occurring in some of the COVID patients…
Read more
5 months ago · 4 likes · 3 comments · Modern Discontent

Part II: The Remdesivir Evidence Before the Pandemic

Remdesivir hasn’t been around for long, but there still exists some in vitro studies of its efficacy. Many of these promising preliminary results lead to its adoption as a possible therapeutic against Ebola. Unfortunately, both the sparse number of studies and questionable results from clinical trials brought Remdesivir’s effectiveness into question.

Modern Discontent
Remdesivir: COVID's Standard of Care that May be Causing more Harm than Good (REVIEW)
I would prefer to keep my evidence data together. However, my analysis of the COVID-19 Clinical Trials are taking up a lot more space than I anticipated. So I have decided to break up the studies from before the pandemic and those looking at evidence against SARS-COV2 directly…
Read more
5 months ago · 4 likes · Modern Discontent

Part III-1: Remdesivir in the Age of COVID

We start to examine the studies of Remdesivir against SARS-COV2 specifically. Once again, in vitro studies showed very promising results. However, the first clinical studies showed inconsistent results, although many factors may attribute to differences in results.

Modern Discontent
Remdesivir: COVID's Standard of Care that May be Causing more Harm than Good (REVIEW)
Even though the purpose of this series is to examine the possible toxicity of Remdesivir, it’s important to examine whether Remdesivir is even effect. In my mind, there’s no point in examining how dangerous a drug is even it’s not even effective. So we’ll take a look at Remdesivir’s effectiveness against SARS-COV2…
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5 months ago · 5 likes · Modern Discontent

Part III-2: Remdesivir in the Age of COVID (Examining the NIH Study)

This post focuses more on the NIH trial (ACCT-1). The interim results of this study was pivotal to Remdesivir’s EUA approval. If we examine the study closely, we will find that the benefits of Remdesivir are highly specific and does not work as a “one size fits all” treatment option.

Modern Discontent
Remdesivir: COVID's Standard of Care that May be Causing more Harm than Good (REVIEW)
Now let’s look at the NIH funded study. Note that this is the “Final Report” which means that this is the only study that really matters (I kid, although I’m pretty sure the NIH and FDA are serious)! This study was most likely used to validate the EUA approval for Remdesivir based on the interim data alone (sound familiar to anyone?). But here we’ll take…
Read more
5 months ago · 5 likes · Modern Discontent

Part IV: Examining the Toxicity & Concluding Remarks

Here we get to the meat of the concern: is Remdesivir actually toxic? The evidence is inconsistent, and although it may not be conclusive, we can at least predict which groups are likely to suffer adverse reactions. I also provide my last remarks on Remdesivir and summarize all of the accumulated evidence.

Modern Discontent
Remdesivir: COVID's Standard of Care that May be Causing more Harm than Good (REVIEW)
So we’ve examined Remdesivir’s therapeutic effects and what factors may play a role in it’s effectiveness. This leads us to the next topic. We’ve heard of anecdotal evidence of renal and hepatotoxicity coming from COVID medical staff as well as the family members of loved ones treated with Remdesivir…
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5 months ago · 4 likes · Modern Discontent

Part V: When you blame everything but the drug.

This is a Paid Subscriber post. Instead of engaging in the precautionary principle and attributing possible toxicity to a drug and all aspects of a drug, it appears that there’s a greater interest in blaming adverse reactions on everything but Remdesivir.

Modern Discontent
Remdesivir: COVID's Standard of Care that May be Causing more Harm than Good (REVIEW)
I think we have covered a lot in regards to Remdesivir and toxicity. However, reports on Remdesivir and its possible toxicity have not been as transparent. In fact, it seems that any reporting revolves around obfuscating any evidence against Remdesivir…
Read more
5 months ago · 1 like · Modern Discontent

Citations:

  1. Eastman, R. T. et al. Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID-19. ACS central science (2020). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7202249/.

  2. Slusarczyk, M., Serpi, M. & Pertusati, F. Phosphoramidates and phosphonamidates (ProTides) with antiviral activity. Antiviral chemistry & chemotherapy (2018). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5971382/.

  3. Veklury® (remdesivir) mechanism of action. HCP Available at: https://www.vekluryhcp.com/about/about-moa.php.

  4. Pardo, J., Shukla, A. M., Chamarthi, G. & Gupte, A. The journey of remdesivir: From ebola to covid-19. Drugs in context (2020). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7250494/.

  5. Agostini, M. L. et al. Coronavirus susceptibility to the antiviral Remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio (2018). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5844999/.

  6. Warren, T. K. et al. Therapeutic efficacy of the small molecule GS-5734 against ebola virus in Rhesus Monkeys. Nature (2016). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5551389/.

  7. Mulangu, S. et al. A randomized, controlled trial of ebola virus disease therapeutics: Nejm. New England Journal of Medicine (2019). Available at: https://www.nejm.org/doi/10.1056/NEJMoa1910993?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed.

  8. Wang, M. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-ncov) in vitro. Cell research (2020). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7054408/.

  9. Williamson, B. N. et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-COV-2. bioRxiv (2020). Available at: https://www.biorxiv.org/content/10.1101/2020.04.15.043166v2.

  10. Veklury (Remdesivir) FACT SHEET FOR HEALTH CARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF REMDESIVIR (GS-5734™ https://www.fda.gov/media/137566/download.

  11. Goldman, J. D. et al. Remdesivir for 5 or 10 days in patients with severe COVID-19. The New England journal of medicine (2020). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7377062/.

  12. “Remdesivir Dosage Guide + Max Dose, Adjustments.” Drugs.com, https://www.drugs.com/dosage/remdesivir.html.

  13. Consortium*, W. H. O. S. T. et al. Repurposed antiviral drugs for covid-19 - interim who Solidarity Trial Results: Nejm. New England Journal of Medicine (2021). Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2023184.

  14. Beigel, J. H. et al. Remdesivir for the treatment of Covid-19 - Final Report. The New England journal of medicine (2020). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7262788/.

  15. Spinner, C. D. et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: A randomized clinical trial. JAMA (2020). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7442954/.

  16. Strimbu, K. & Tavel, J. A. What are biomarkers? Current opinion in HIV and AIDS (2010). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3078627/.

  17. Vroon, David H. “Aminotransferases.” Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd Edition., U.S. National Library of Medicine, 1 Jan. 1990, https://www.ncbi.nlm.nih.gov/books/NBK425/.

  18. Kalakonda, Aditya. “Physiology, Bilirubin.” StatPearls [Internet]., U.S. National Library of Medicine, 16 Sept. 2021, https://www.ncbi.nlm.nih.gov/books/NBK470290/.

  19. “Creatinine Tests.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 25 Feb. 2021, https://www.mayoclinic.org/tests-procedures/creatinine-test/about/pac-20384646.

  20. “Electrocardiogram (ECG or EKG).” Www.heart.org, https://www.heart.org/en/health-topics/heart-attack/diagnosing-a-heart-attack/electrocardiogram-ecg-or-ekg.

  21. van Laar, S. A. et al. Liver and kidney function in patients with covid-19 treated with Remdesivir. British journal of clinical pharmacology (2021). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8251044/.

  22. Sodeifian, F. et al. Drug-induced liver injury in COVID-19 patients: A systematic review. Frontiers in medicine (2021). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8488138/.

  23. Zampino, R. et al. Liver injury in remdesivir-treated COVID-19 patients. Hepatology international (2020). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7386240/.

  24. Montastruc, F., Thuriot, S. & Durrieu, G. Hepatic disorders with the use of Remdesivir for coronavirus 2019. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2020). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7381904/.

  25. Center, 1S. F. M. Hepatotoxicity of Remdesivir for COVID-19: Systematic Review and Meta-Analysis. LWW Available at: https://journals.lww.com/ajg/Fulltext/2020/10001/S1027_Hepatotoxicity_of_Remdesivir_for_COVID_19_.1028.aspx.

  26. Fan, Q., Zhang, B., Ma, J. & Zhang, S. Safety profile of the antiviral drug remdesivir: An update. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2020). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7373689/.

  27. Gérard, A. O. et al. Remdesivir and acute renal failure: A potential safety signal from disproportionality analysis of the Who Safety Database. American Society for Clinical Pharmacology and Therapeutics (ASCPT) (2021). Available at: https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.2145.

  28. Chouchana, L. et al. Kidney disorders as serious adverse drug reactions of Remdesivir in coronavirus disease 2019: A retrospective case-noncase study. Kidney international (2021). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7907730/.

  29. Ackley, T. W., McManus, D., Topal, J. E., Cicali, B. & Shah, S. A valid warning or clinical lore: An evaluation of safety outcomes of Remdesivir in patients with impaired renal function from a multicenter matched cohort. Antimicrobial agents and chemotherapy (2021). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7849020/.

  30. Delanaye, P., Cavalier, E. & Pottel, H. Serum creatinine: Not so simple! Nephron (2017). Available at: https://www.karger.com/Article/FullText/469669.

  31. Nabati, M. & Parsaee, H. Potential cardiotoxic effects of Remdesivir on cardiovascular system: A literature review. Cardiovascular toxicology (2021). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8511861/.

  32. Brunetti, N. D. et al. Safety and heart rate changes in covid-19 patients treated with Remdesivir. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases (2021). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8451471/.

  33. Abdelmajid, A. et al. Remdesivir therapy causing bradycardia in COVID-19 patients: Two case reports. IDCases (2021). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8359645/.

  34. Gubitosa, J. C. et al. Marked sinus bradycardia associated with Remdesivir in COVID-19: A case and literature review. JACC. Case reports (2020). Available at: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7598346/.

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