Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19, 2024, Hanson et al

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Low ferritin levels for pwME has been a mystery. My levels were normal when I was tested by an Internist during the first year of illness, but rapidly started decreasing for no apparent reason for many years after. I took iron supplements regularly. No one could figure it out why.

I don't think it was from inflammation in my case b/c I had a c-reactive protein test and it was normal.

https://www.cam.ac.uk/research/news...enews&utm_medium=miragenews&utm_campaign=news

 

If you had inflammation or infection in your body your ferritin (iron stores) would have ended up higher than normal, not lower, because ferritin is a positive Acute Phase Protein. The body has iron in the blood stream (referred to in testing as serum iron) and also stores it in ferritin. The iron in the blood stream is available to pathogens so the body keeps that iron to a minimum, lowers haemoglobin, and stores the "excess" iron in ferritin (which pathogens can't get iron from thus reducing their chances of reproducing), which is why ferritin goes up in the case of inflammation and infection.

Since your ferritin levels were decreasing it would suggest that something (I don't know what) was preventing you from absorbing iron from your diet, or perhaps you were losing blood somewhere, or you developed one of the more unusual forms of anaemia. Whether your serum iron was going up while your ferritin was going down without being noticed could happen because doctors rarely do iron studies testing (which includes a serum iron test) because they think ferritin tells them everything they need to know about iron.

 

I tried a gluten free diet for almost a year even though I tested negative for gluten sensitivities, I cooked with cast iron pots, ate plenty of liver and roasts with vitamin C, took digestive enzymes that might have helped a little, eradicated h pylori, ate fermented foods . . . I dunno. My functional/integrated doctor was perplexed.

I also did an iron metabolism test. The TIBC and UIBC were both on the lower end. It indicates the that the storage capacity of iron is almost insufficient. A further decrease of UIBC would have led to free iron in circulation according to my records. This produces oxidative stress itself. I also had high oxidative stress.

 

Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19
Hanson, Aimee L.; Mulè, Matthew P.; Ruffieux, Hélène; Mescia, Federica; Bergamaschi, Laura; Pelly, Victoria S.; Turner, Lorinda; Kotagiri, Prasanti; Göttgens, Berthold; Hess, Christoph; Gleadall, Nicholas; Bradley, John R.; Nathan, James A.; Lyons, Paul A.; Drakesmith, Hal; Smith, Kenneth G. C.

Persistent symptoms following SARS-CoV-2 infection are increasingly reported, although the drivers of post-acute sequelae (PASC) of COVID-19 are unclear. Here we assessed 214 individuals infected with SARS-CoV-2, with varying disease severity, for one year from COVID-19 symptom onset to determine the early correlates of PASC.

A multivariate signature detected beyond two weeks of disease, encompassing unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression and emerging stress erythropoiesis; differentiated those who reported PASC months later, irrespective of COVID-19 severity. A whole-blood heme-metabolism signature, enriched in hospitalized patients at month 1–3 post onset, coincided with pronounced iron-deficient reticulocytosis. Lymphopenia and low numbers of dendritic cells persisted in those with PASC, and single-cell analysis reported iron maldistribution, suggesting monocyte iron loading and increased iron demand in proliferating lymphocytes.

Thus, defects in iron homeostasis, dysregulated erythropoiesis and immune dysfunction due to COVID-19 possibly contribute to inefficient oxygen transport, inflammatory disequilibrium and persisting symptomatology, and may be therapeutically tractable.

Link | PDF (Nature Immunology) [Open Access]

 

Commentary in Alterations of iron homeostasis as a potential druggable driver of long COVID (2024, Nature Immunology)

 

Are they checking your ferritin?

My sister has low iron levels from Hashimoto. Did you get your thyroid levels tested?

 

What kind of supplements are you taking? Are they iron salts? Heme supplements? If they don't work because you don't absorb iron very well, and food doesn't help either, then perhaps you might need an iron infusion.

 

I've seen occasional references to that but have never read any experiences of it. I hope any side effects are minor.

I'm assuming you've seen the Patient Information Leaflet :

https://www.nps.org.au/medicine-finder/maltofer-syrup#full-pi

If you are taking an iron syrup, remember to rinse your mouth with water after taking each dose. Liquid iron products can blacken the teeth.

 

I just want to make a comment about iron supplements in general. I was told to take Palafer many years ago and it was too much (300 mg) to take at once since our body only absorbs 10% and the rest has to be filtered out through the liver which makes us feel sick.

This was the best iron supplement I took rec by my integrative/functional M.D. It was developed by a biochemist who specializes in iron and owns a compounding pharmacy in my area. I've seen him several times for other tests years ago.

https://www.youtube.com/watch?v=Esl8mmE8J_c

 

Good that you're being checked out for possible gastro bleeds.

In case it's relevant, a consultant haematologist told me that it is better to take iron supplements every second day rather than every day - you actually absorb more that way. This was a moot point for me as I can't tolerate any of them, but might be worth looking into for you.

I developed severe anaemia a couple of years ago and after outruling a gastric bleed, it was rectified with an iron infusion and vitamin C (which helps iron absorption) - both were recommended by the haematologist. (They recommended 2 infusions but long story short, I didn't get the second.) I also had a 1-unit blood transfusion which was recommended by a different doctor - my understanding is that this was not necessary and should probably not have been given. But I did have tachycardia (due to severe anaemia) so they weren't messing around. I have been able to maintain normal levels since with a vitamin C supplement once a day, and a medication to reduce menstruation.

 

These studies seem to confirm alternate day dosing of iron supplements being preferable to daily dosing - they were done in women only though.

https://pubmed.ncbi.nlm.nih.gov/314...eted women without,is given on alternate days.

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00463-7/fulltext

 

My daily dose of iron supplementation was 27mg w vitamin C. It took 9 months to bring my ferritin up to 55 from 5 and it would drop back down to 14 within 2 months after I stopped taking iron.

Alternate-day administration of 100 and 200 mg taken from the link posted above would make sense b/c it's quite a high amount.

 

Not being able to tolerate oral iron is a good reason for an iron infusion. Maybe you could ask for referral to a haematologist if you aren't seeing one already?