Inspired by Coronavirus 2019 (COVID-19)- Using Ascorbic Acid and Zinc Supplementation (COVIDAtoZ)
This study protocol differs from other iterations as the Covid-19 death toll reaches 400,000. There’s a nice zinc supplement study zinc supplement study: A single-center, prospective, open label four arm study (1. Zinc only 2. Zinc and ascorbic acid 3. Ascorbic acid only 4. Standard of care.
Looking Back, comparing two coppers on immune parameters in chickens
The updated plan would be to perform blood draws only after the patient has a negative PCR test. Time to negative PCR test will be a new outcome measure. By restricting blood draws, money could be saved towards including an active comparatar rather than a placebo. Cupric glycinate is one such active compound (Jarosz 2018). These authors tested the hypothesis that Cu(II)Gly could improve cell based (T cell lineages) and humoral (cytokine) immune parameters in boiler chickens. These authors also included the plasma based copper carrier protein ceruloplasmin and erythrocyte Cu/Zn superoside dismutase (SOD) in their analyses. Chickens were treated with two forms of cupric copper (CuSO4 and Cu(II)Gly) phytase (F) A phytase (myo-inositol hexakisphosphate phosphohydrolase) is any type of phosphatase enzyme that catalyzes the hydrolysis of phytic acid (myo-inositol hexakisphosphate) – an indigestible, organic form of phosphorus that is found in many plant tissues. The roosters were suplemented wtih 16 mg Cu per kg feed in addition to the normal requirements for Ross 308 broiler chickens.
Note that cupric glycinate out performs CuSO4. The way the data were presented, it is kind of hard to tell if the phytase enzyme did any good. These authors also looked at Interleukin 2 (IL-2) and IL-10. Both copper compounds greatly increased IL-10 from day 20 to day 42.
Lymphocyte sub populations
These authors characterized lymphocytes (immune cells associated with antibody production) based on surface markers. CD3+ is a T-cell marker. CD4+ marks the cell as a T helper cell. CD8+ marks a T cell as a a cytotoxic T cell that are best known for killing cancer cells. CD25 is the IL-2 receptor. It is found on activated T and B cells. MHC class II are surface proteins that present antigens on macrophage and dendritic cells, to name a few. Bu-1a is an antigen found on bursal cells of one day old hens.The Bursa of Fabricius is a lymphoid organ found only in birds
- CD3+CD4+ Phytase and Cu-Gly seemed to have elicited the biggest increases in the CD4+ sub population.
- CD3CD8+ Only copper glycinate with phytase increased this marker at day 42.
- CD25+ Cu-Gly increased the IL-2 receptor positive cells on day 20 and 42 compared to day 0. Phytase was not reported to increase IL-2 receptor presence.
- MHC class II Cu-Gly, with and without phytase, increased the percent positive on days 20 and 42 compared to day 0.
- Bu-1a Both copper supplements result in significant (p<0.05) but slight increases in this antigen marker. Phytase did not seem to do much.
The take home is that the type of Cu(II) made a difference in the immune systems in these boiler chickens.
Looking forward, Comparing types of copper in humans
The eye opening and worthy of emulation thing is that they expose no laboratory to personnel to Covid. It might also cut down on cost for C LAB Pharma if we only do blood work on day 28. Also, having an IRB working with us from the start will probably save time in the long run.
These are some proposed arms of a Covid study
- 2 mg Cu per day, 6 mg Cu 48 hours pyrexia in the form of Cu(I)NA2
- 2 mg Cu per day, 6 mg Cu 48 hours pyrexia in the form of Cu(II)glycinate
- Covid-19 standard of care
Jarosz ŁS, Marek A, Grądzki Z, Kwiecień M, Kaczmarek B. The effect of feed supplementation with a copper-glycine chelate and copper sulphate on selected humoral and cell-mediated immune parameters, plasma superoxide dismutase activity, ceruloplasmin and cytokine concentration in broiler chickens. J Anim Physiol Anim Nutr (Berl). 2018 Feb;102(1):e326-e336. doi: 10.1111/jpn.12750. Epub 2017 Jun 12. PMID: 28603872.