Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors?, 2021, Mantovani et al

[Wyva]

Abstract

SARS-CoV-2 survivors may report persistent symptoms that resemble myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We explored (a) ME/CFS-like symptom prevalence and (b) whether axonal, inflammatory, and/or lung changes may contribute to ME/CFS-like symptoms in SARS-CoV-2 survivors through clinical, neuropsychiatric, neuropsychological, lung function assessment, and serum neurofilament light chain, an axonal damage biomarker.

ME/CFS-like features were found in 27% of our sample. ME/CFS-like group showed worse sleep quality, fatigue, pain, depressive symptoms, subjective cognitive complaints, Borg baseline dyspnea of the 6-min walking test vs. those without ME/CFS-like symptoms. These preliminary findings raise concern on a possible future ME/CFS-like pandemic in SARS-CoV-2 survivors.


Open access: https://link.springer.com/article/10.1007/s13365-021-01002-x

 

[alex3619]

I would love to tap like to this but its a nightmare scenario. Good for the prospect of real research funding, bad for everyone else. So consider this a like for the post, a like for the research prospects, but a dislike for the risk of all those new ME patients.

PS Only partly read the paper so far, but it uses ME ICC criteria, not CFS criteria. Interesting.

 

[Hutan]

Authors: Elisa Mantovani, Sara Mariotto, Daniele Gabbiani, Gianluigi Dorelli, Silvia Bozzetti, Angela Federico, Serena Zanzoni, Domenico Girelli, Ernesto Crisafulli, Sergio Ferrari & Stefano Tamburin

All from the University of Verona, Italy - most with a neurological or medical background.

I don't know why they didn't say in the abstract when (in terms of time after illness onset) the people were evaluated. The evaluation was done at least 6 months after Covid-19.

Inpatients and outpatients positive to SARS-CoV-2 PCR testing in February–May 2020 were recruited at the Department of Internal Medicine, Verona University Hospital, Italy, after informed consent.

After screening the initial cohort (N = 131) for eligibility (Fig. 1), we included 37 patients (age 51.9 ± 10.9; 25 men, 12 women), of whom 10 were classified as ME/CFS + (age 50.7 ± 12.3; 5 women) and 27 as ME/CFS- (age 52.3 ± 10.5; 7 women; Table 1).

So, inpatients and outpatients at a hospital in Verona. The investigators screened out a lot of people, mostly because they only accepted people aged less than 65 years. Yes, they had to have 'post-exertional neuroimmune exhaustion.

Look at the gender split in the 'ME/CFS-like' group - only 50% women (although I guess 10 in total is a small number). Edit - and there were fewer women in the total sample.

Socio-demographic data, baseline comorbidities, and clinical and inflammatory features of SARS-CoV-2 infection did not differ between groups.

Sleep quality, fatigue, pain, and depressive symptoms were significantly more common and more severe in the ME/CFS + vs. ME/CFS − group (Fig. 2). Anxiety did not differ between groups.

On cognitive problems - they couldn't measure any problems, but the people with ME/CFS+ complained about problems. Therefore, it's probably functional.

ME/CFS + patients reported higher subjective cognitive complaints than the ME/CFS- group, even in the absence of overt cognitive dysfunction. The subjective–objective cognitive mismatch suggests that ME/CFS-like cognitive complaints may fall within the functional cognitive disorder spectrum (Teodoro et al. 2018). Alternatively, the tools we used could be not calibrated to capture subtle cognitive impairment.

Neurofilament light chain levels normal - so probably no axonal damage. How robust is that statement? Does that mean there has been no nerve damage?

Serum NfL levels were normal except in one ME/CFS-like patient, and we found no differences when comparing ME/CFS + vs. ME/CFS − . This finding suggests that axonal damage does not seem to underlie ME/CFS-like symptoms in SARS-CoV-2 survivors and requires confirmation in larger studies.

Lung function was fine, but people with ME/CFS+ perceived more breathlessness, suggesting a functional problem.

Conclusion:

Our results suggest that ME/CFS-like symptoms in patients with COVID-19 may fall under functional neurological syndromes

The suggested etiology seems to be 'the fatigue and pain that is normal when recovering from an illness causes excessive monitoring of symptoms, resulting in an inaccurate interpretation of reality'.

It does not bode well for care of people with ME/CFS in Verona.

 

[Hutan]

This 2020 paper:
Blood Neurofilament Light Chain: The Neurologist’s Troponin? Thebault et al
suggests that the techniques to pick up the low levels of NfL in blood (as opposed to CSF) have just been developed.

In a longitudinal study of NfL levels before and after intrathecal catheter insertion, NfL in both CSF and serum peaked at 1-month post-surgery, returning to baseline after 6 to 9 months [16]. In longitudinally sampled MS patients around the time of relapse, levels increasing 5 months before, peaking at clinical onset, and recovery within 4–5 months

So, it is possible that there was some nerve damage at the onset of ME/CFS symptoms, in which case the NfL markers would be gone by the time the Verona team was looking for them. Peripherin seems to be a neuropolymer in the peripheral nervous system, but doesn't seem to be included in the light chain group - so I think damage to peripheral nerves probably would not have been picked up in the Verona analysis.

I'll make a new thread for this NfL paper - it's interesting.

 

[Midnattsol]

Just a comment on the cognitive function. I did a modified WAIS test since I complained about lack of memory, low concentration etc. I don't remember the exact value, but if you scored above 60-80% of the "general public" for many of the domains they tested, that would classify as not being a problem. They didn't even bother with numbers above the threshold for "high functioning". Nevermind that for you personally there could still be quite a drop in function (this also holds true for the range of 'normal' values). Without pre-illness test scores you can't really say if functioning has been impaired. And even a small impairment, which you could probably live with without issue will probably be worthy of complaints in the beginning as you get used to your "new normal".

 

[alex3619]

Without pre-illness test scores you can't really say if functioning has been impaired.

I had a simple dementia verbal memory test over a decade ago. I thought it probably a waste of time but went along with it. I aced it, only missing I think one or two items on a long list over three times. Curiously it was the second iteration where I missed one or two, not the first. My specific cognitive deficits were ignored, and a long list I gave them first was placed in the little round filing system on the floor. Cognitive tests that do not address a patient's specific issues are deceptive at best, usually useless, and frequently harmful by leading to dubious conclusions.

 

[alex3619]

Using poor cognitive testing protocols might get some results that are useful in extremely large cohorts where small differences in cognition might be detected. Not so great in tiny cohorts, deceptive as I already stated.

 

[Mithriel]

I had a simple dementia verbal memory test over a decade ago. I thought it probably a waste of time but went along with it. I aced it, only missing I think one or two items on a long list over three times. Curiously it was the second iteration where I missed one or two, not the first. My specific cognitive deficits were ignored, and a long list I gave them first was placed in the little round filing system on the floor. Cognitive tests that do not address a patient's specific issues are deceptive at best, usually useless, and frequently harmful by leading to dubious conclusions.

Most people get better at these tests as they get the hang of it. People with ME get tired so their score drops but they never repeat the test often enough.

The deficits in ME are actually very easy to find but they are so unique to us that we need our own specialised tests. In the 80s I read about a doctor who got his nurse to give patients in the waiting room a clip board and asked them to write out some of their symptoms. In people with ME their writing deteriorated badly.

Studies have shown that people with ME can often do cognitive tests but that they use more effort to do so.

If scientist thought about ME as a physical disease, let's lose "functional" as a description for a start, then they would be more willing to look at what the consequences would be of having a problem with energy production.
Then it would be possible to develop simple (cheap!) tests that would be indicative of the disease.

 

[alex3619]

Studies have shown that people with ME can often do cognitive tests but that they use more effort to do so.

Coming back from that testing was a nightmare. My energy crashed so badly I could not lift my feet even an inch, so could not use even a single step. I eventually found a taxi, came home, and crashed into bed. It was a cognitive test but I physically crashed. They never consider energy deficits from my experience.

 

[rvallee]

"Emerging", uh? Sounds a lot like "here's my 6' 200 lbs child". It's been 16 months.

Fitting that such people would trot out the functional crap.

 

[Snow Leopard]

Just a comment on the cognitive function. I did a modified WAIS test since I complained about lack of memory, low concentration etc. I don't remember the exact value, but if you scored above 60-80% of the "general public" for many of the domains they tested, that would classify as not being a problem.

Exactly. Unless the test was performed prospectively (before illness) for comparison, claims that there is no reduction in performance are not valid.

 

[ahimsa]

In case it's of use here's a twitter thread from ME Association about this research paper:

Quote from Dr. Shepherd: "Some of the content and referencing in this paper indicates that this research group from Verona in Italy are not used to working with ME/CFS patients and are not fully up to speed on ME/CFS research. However, it's good to see that researchers are taking the link between Long Covid and ME/CFS seriously and are starting to publish papers on the overlaps."