Trial Report Possible Markers For Myalgic Encephalomyelitis / CFS Developed In Long Covid: Utility Of Serum Ferritin And Insulin-like Growth Factor-I,2023,Yamamoto

Merged thread
Final paper abstract here



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Editorial: Ferritin and myalgic encephalomyelitis/chronic fatigue syndrome in post COVID-19, an unexpected facet of the hyperferritinemic syndrome?

Coronavirus disease 2019 (COVID-19) has provoked a catastrophic medical emergency worldwide [1]. In the course of time from the beginning of this pandemic, subacute and long-term effects in patients suffering from COVID-19 have been increasingly recognised [1,2]. Thus, the term “long-COVID-19” has been proposed to describe this collection of signs and symptoms which may continue or sometimes develop following the SARS-CoV-2 infection. The latter is defined as post-COVID-19 syndrome [3]. In a large percentage of these patients, mental health problems and fibromyalgia have been also recognised [[3], [4], [5]]. Interestingly, many patients could experience severe fatigue in a clinical setting of myalgic encephalitis/chronic fatigue syndrome (ME/CFS), even several months after SARS-CoV-2 infection [6]. In this context, low level inflammation and hypoperfusion have been recently proposed as potential pathomechanisms of occurrence of ME/CFS [7].

On these bases, possible predictors of ME/CFS have been recently investigated in 234 patients with post-COVID-19 syndrome [8]. To date, almost 60% of evaluated patients had fatigue symptoms, and 21.4% met classification criteria for ME/CFS. The authors performed a deep assessment of laboratory features of included patients, stratifying the results in 3 groups, namely patients meeting classification criteria for ME/CFS, patients with fatigue but not reaching the classification criteria for ME/CFS, and patients without fatigue.

Open access, https://www.sciencedirect.com/science/article/pii/S0022399923000880

 

Know what else has provoked this catastrophic medical emergency worldwide?

Still, on the plus side, it's an editorial in J Psychosomatic Research that discusses biological underpinnings of ME/CFS. Also the CSF-to-CFS ratio is a quite restrained 3:21 in this corrected proof.

On the minus side —

Gonna need some emojis for that one.

You guys ... this is the March 15th edition, you're two weeks early.

 

Not sure what to make of this publication e.g. I would have expected this to have emerged a long time ago.

If iron transport/metabolism is relevant, in a large proportion of cases, then I'd expect seething to turn up in the GWAS study.

 

That was my first thought, but might it be something that could easily be overlooked? If the ferritin levels were higher than normal but not high enough to suggest iron overload, and patients had none of the symptoms classically associated with iron metabolism or storage issues, it wouldn't even raise an eyebrow in most primary care physicians. It probably wouldn't even be noted in some ME studies.

 

My aunt who is severely affected has humongous ferritin levels . No problems on iron panel and no haemachromatosis. Ferritin us an inflammatory marker .
Her sister , who dosn't have ME developed very high ferritin levels too . Again iron panel ok.
Recently diagnosed ( after bring fobbed off re back pain ) with osteo arthritis - so inflammation high .

Ferritin isn't only about iron.

 

When I first became ill in 2002 with extreme fatigue (the beginning of my ME I believe) I went to the doctors and they found my ferritin levels were high, 760, normal range 30-330, and remained high so they sent me to the blood specialists who tested me for hemochromatosis (negative) and checked my liver etc (all ok). In the end they gave up and said they didn't know what was causing it but suggested that high ferritin levels can be a sign of inflammation. They said that 760 is not that high and it probably wasn't the cause of my fatigue. They mentioned that donating blood was one way of reducing high ferritin levels. The levels eventually came down under the 330 mark and the fatigue went away for a while and no blood test since has as far as I know has ever shown it to be high. But it is a bit suspicious that the level was high when my ME started.

 

My ferritin levels dropped below 6 soon after M.E onset and kept dropping. I had to take iron supplements regularly for decades.

 

To expand a little on this, ferritin biology is not fully understood. It's considered an acute phase reactant in which it may be a marker of cell damage. Serum ferritin levels can be used to estimate body iron stores but it's not so straightforward. Liver biopsy or MRI are often used to try and get a better estimate in iron-overload conditions.

There was a special issue on Advances in Iron Metabolism and Anemia in Metabolites in 2022, containing —

The Role of Ferritin in Health and Disease: Recent Advances and Understandings (2022)

And from Chemistry and biology of ferritin (2021, Metallomics) —

Jo would have in-depth knowledge on this as it's a marker in rheumatoid arthritis and other chronic inflammatory conditions.

 

Mine has been low several times. Once it was 2 or 3. I don't notice when it's under the limit due to ME, so have to check regularly and also take supplements. Have any of you had too high levels?

 

Last time I had it checked it was slightly over 1000.

 

My ferritin levels were always between 27 to 32 until menopause when they went up to 134. Since being diagnosed with MGUS and Sjogren's just over four years ago they have been consistently going down. When they were checked two years ago they were down to 56 and on Monday I get the results from testing done in the ER on Wednesday.

 

As I've said elsewhere on the forum, my ferritin has also been very high since I came down with ME/CFS. After tests for haemochromatosis and fatty liver came back clear, doctors just shrugged their shoulders.

My father's ferritin has been similarly elevated for the past 7-8 years without any explanation or much interest from his doctor.

 

This is quite good re heme/ ferritin functions etc .
Touches on inflammation, signalling etc.

ETA low copper status affects ferritin formation .


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961798/

 

I am afraid I never took much interest in ferritin. It mostly seemed to be a red herring, other than in the context of haemochromatosis. Other things more directly reflect inflammation.

 

Mine can get very low, and are never high, and I also have inflammation

 

Any clues re low hemoglobin --- not sure what consequences of marginally low iron would be.

 

Although labs aren't moving quickly on this in the UK, NICE has brought out guidelines for iron deficiency anaemia (last revised Nov 2021) that mention ferritin and it raised the lowest part of the range from 13 to 30 mcg/L. The standard range for women for many years was 13 - 150 mcg/L, and in many labs it still is.

I don't know if people who aren't in the UK can read NICE guidelines.

https://cks.nice.org.uk/topics/anaemia-iron-deficiency/diagnosis/investigations/

In the above link, in the section on "Interpreting ferritin levels" :

The problem is that people can have very low ferritin and yet still have haemoglobin which is high enough not to be classified as anaemia.

I don't know what guidelines doctors actually use, but in my case it seems if my haemoglobin is in range then I don't need to be treated, even if my ferritin is very low in range. And of course, serum iron is almost never tested in primary care, as far as I'm aware. I found one reference in my records to serum iron being under range and it was never mentioned to me at the time, nor was it tested again.

On the same link as above :

I bought a copy of my medical records a few years ago and discovered that a normal course of events was :

1) Get a Full Blood Count (FBC) done.

2) If haemoglobin is within "normal" range nothing else needs to be done. So ferritin was rarely measured.

It seems, at least in my case, that doctors use the FBC (haemoglobin and MCV) and ferritin measurements in whichever way they can to reduce the chance of having to spend money on a prescription for iron supplements. So I could have low in range ferritin and bottom of range haemoglobin and/or MCV and I would not be given a prescription for iron.

One thing that improved my life enormously was when I found out that I could buy prescription-strength iron supplements without a prescription. I could also pay for an iron panel to be done privately without requiring a doctor to get involved.

...

Regarding the top of the range for ferritin and having high ferritin...

I'm aware that one lab in the UK has fairly recently changed its upper level of the range for men and post-menopausal women to 650 mcg/L. That is an eye-watering jump from a top of range of 150 mcg/L which that lab still uses for the top of range in women before the menopause.