Spring solved Covid-19

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So long to Covid-19 treatment blogs: Synergy and the zinc theory

I spent a few weeks tracking down the information on COVID-19, hydroxychloroquine / chloroquine, zinc, and azithromycin. In that process I found some bloggers who are doing a much, much better job at exploring the research than I am (shout outs to ASBMB, NephJC again, and “Hello!” Derek Lowe. Never did I think I’d find myself high-fiving a pharmacologist, but here I am). They’ve pointed me in some interesting directions, including back to focusing on my patient base. Unless there’s a compelling reason that relates specifically to pregnancy or pediatrics, I think I’ll let them do the commentary from now on. Preview: There is, and I’m going to write about it next!

Before I totally give up on life, let me help connect a few dots. First, chloroquine studies back the zinc + hydroxychloroquine combination. The two drugs aren’t identical, let’s say that first. But ultimately chloroquine increases the permeability of cell membranes to zinc, and zinc does all kinds of lovely anti-microbial things inside a cell. This includes red blood cellschloroquine can cross those membranes, which is likely the reason it’s so good against the organism associated with malaria. There are also studies that point to zinc deficiency being related to anemia. Guess who also tends to get anemia? People with respiratory infections.

Computers aren’t clinical research

Speaking of blood, a few friends forwarded me a blog based on a publication that claimed to crack the code on COVID-19. I have seen the research on the S spike protein and ACE-2 in the cell membrane all over the place, but this suggested the virus attacked hemoglobin, knocked an iron off the cell, then induced all kinds of free radical damage. This was a competing theory I spent days tracking down. The blogger has a unique insight. He strings together some interesting clinical science, but I don’t know that the paper confirms what he’s saying it does. Ultimately it lead me to a few things.

  1. This paper is based on a computer model. The computer program was instructed to make best case scenarios for the interaction between the virus and hemoglobin.
  2. Other models of COVID-19 are more compelling. Derek Lowe points to an x-ray crystallography study showing the interaction between the ACE-2 and spikes, and another suggesting that the affinity for ACE-2 isn’t as strong for Covid-19 as it is for SARS.
  3. The x-ray crystallography study, which is super-geeky and well done, pointed out that in their real-life models of interaction the COVID-19 and ACE-2 would only bind in a rather finicky way. Therefore, we can’t really apply the favorable manipulation to the real world. It doesn’t seem to happen that way.
  4. This isn’t to say the whole theory is wrong; but so far it isn’t backed up by the individual paper.

Which brings us to Z-paks

I’ve been right there with most of you- why are they recommending a very effective anti-biotic for a virus? Well, why are they recommending a very effective anti-malarial (parasitic) for a virus? Because it’s not the first time, there’s a little evidence, and when people are desperate they try things off-label.

I will again re-iterate what I said before, and I’m now seeing echoed by people far smarter than me (Hello again, Dr. Lowe, and CDC Director Fauci has said it until he’s blue in the face): The French hydroxychloroquine study sample was small and not very well done. They only used z-packs when it looked like the patient had a bacterial infection. There is, however, a precedent here.

Researchers who wanted to try azithromycin for the common cold ran an experiment with COPD patients. They did find that this class of drugs has an impact on pieces of the inflammatory cascade that impacts Covid-19 patients. So at its worst, the drug controls inflammation. At it’s best, it also addresses underlying bacterial infections.

Well, that’s not completely accurate. At it’s worse we all end up dying from MRSA or some other bacteria that becomes resistant to z-paks that we have no way of defending ourselves against. But that’s a future-us problem, amirite?

Happy Spring, Mr. President

As of yesterday it appears that people have had enough. The numbers in my home state are flattening out among seniors, the public is getting antsy, and reading the room the President made a declaration. It seems that Covid-19 has been solved in a lot of places and we can now 1-2-3 step our way out of this. I’ll credit Vitamin D down here, and I’m sure the social distancing and masks some folks have been wearing have helped. I think washing one’s hands is a good idea. But I still have major concerns for people of color, the Vitamin D deficient, and those young people who don’t know their blood pressure is too high. If this country is going to see a rebound, it’s going to be among those folks. Again, I pray for an early spring in the Midwest.

References

Victor Ferrari, David J. Cutler, “Uptake of chloroquine by human erythrocytes.” Biochemical Pharmacology, Volume 39, Issue 4, 1990,
Pages 753-762, ISSN 0006-2952, https://doi.org/10.1016/0006-2952(90)90155-E.

Lisa A Houghton, Winsome R Parnell, Christine D Thomson, Timothy J Green, Rosalind S Gibson, Serum Zinc Is a Major Predictor of Anemia and Mediates the Effect of Selenium on Hemoglobin in School-Aged Children in a Nationally Representative Survey in New Zealand, The Journal of Nutrition, Volume 146, Issue 9, September 2016, Pages 1670–1676, https://doi.org/10.3945/jn.116.235127

Liu, J., Cao, R., Xu, M. et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov 6, 16 (2020). https://doi.org/10.1038/s41421-020-0156-0

Menzel M, Akbarshahi H, Bjermer L, Uller L. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients. Sci Rep. 2016;6:28698. Published 2016 Jun 28. doi:10.1038/srep28698

Meng Yuan, Nicholas C. Wu, Xueyong Zhu, Chang-Chun D. Lee, Ray T. Y. So, Huibin Lv, Chris K. P. Mok, Ian A. Wilson “A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV” Science. Published Online 03 Apr 2020 DOI: 10.1126/science.abb7269

Ning Dong, Xuemei Yang, Lianwei Ye, Kaichao Chen, Edward Wai-Chi Chan, Mengsu Yang, Sheng Chen “Genomic and protein structure modelling analysis depicts the origin and infectivity of 2019-nCoV, a new coronavirus which caused a pneumonia outbreak in Wuhan, China.” bioRxiv 2020.01.20.913368; doi: https://doi.org/10.1101/2020.01.20.913368

Wenzhong, liu; Hualan, Li (2020): COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.11938173.v7

Yayon, Avner & Ginsburg, Hagai. (1982). The transport of chloroquine across human erythrocyte membranes is mediated by a simple symmetric carrier. Biochimica et Biophysica Acta (BBA) – Biomembranes. 686. 197-203. 10.1016/0005-2736(82)90113-4.