Chronic COVID-19 Syndrome and ME/CFS following the first pandemic wave in Germany. Scheinbogen et al 2021, pre-print

[Murph]

Abstract

Objective Characterization of the clinical features of patients with persistent symptoms after mild to moderate COVID-19 infection and exploration of factors associated with the development of Chronic COVID-19 Syndrome (CCS).

Methods Setting: Charité Fatigue Center with clinical immunologists and rheumatologist, neurologists and cardiologists at Charité University hospital.

Participants: 42 patients who presented with persistent moderate to severe fatigue six months following a mostly mild SARS-CoV-2 infection at the Charité Fatigue Center from July to November 2020.

Main outcome measures: The primary outcomes were clinical and paraclinical data and meeting diagnostic criteria for Chronic Fatigue Syndrome (ME/CFS). Relevant neurological and cardiopulmonary morbidity was excluded.

Results The median age was 36.5, range 22–62, 29 patients were female and 13 male. At six months post acute COVID-19 all patients had fatigue (Chalder Fatigue Score median 25 of 33, range 14–32), the most frequent other symptoms were post exertional malaise (n=41), cognitive symptoms (n=40), headache (n=38), and muscle pain (n=35).

Most patients were moderately to severely impaired in daily live with a median Bell disability score of 50 (range 15–90) of 100 (healthy) and Short Form 36 (SF-36) physical function score of 63 (range 15-80) of 100. 19 of 42 patients fulfilled the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

These patients reported more fatigue in the Chalder Fatigue Score (p=0.006), more stress intolerance (p=0.042) and more frequent and longer post exertional malaise (PEM) (p=0.003), and hypersensitivity to noise (p=0.029), light (p=0.0143) and temperature (p=0.024) compared to patients not meeting ME/CFS criteria.

Handgrip force was diminished in most patients compared to healthy control values, and lower in CCS/CFS compared to non-CFS CCS (Fmax1 p=0.085, Fmax2, p=0.050, Fmean1 p=0.043, Fmean2 p=0.034, mean of 10 repeat handgrips, 29 female patients). Mannose-binding lectin (MBL) deficiency was observed frequently (22% of all patients) and elevated IL-8 levels were found in 43% of patients.

Conclusions Chronic COVID-19 Syndrome at months 6 is a multisymptomatic frequently debilitating disease fulfilling diagnostic criteria of ME/CFS in about half of the patients in our study. Research in mechanisms and clinical trials are urgently needed.

https://www.medrxiv.org/content/10.1101/2021.02.06.21249256v1

 

[pattismith]

Mannose-binding lectin (MBL) deficiency was observed frequently (22% of all patients) and elevated IL-8 levels were found in 43% of patients.

 

[nerd]

Let's see if they get it published with this title. I think I remember a case where authors were asked to remove "CFS/ME" completely and any association with it. But this is the main point of this study after all.

 

[pattismith]

Strange that I can't see much difference between chronic covid meeting CFS/ME criteria and chronic covid non meeting.....

Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany – a first analysis of a prospective observational study (medrxiv.org)

Mannose-binding lectin (MBL) deficiency was observed frequently (22% of all patients) and elevated IL-8 levels were found in 43% of patients.

I just want to add that MBL deficiency may just increase the overall risk to develop symptomatic covid infection.

 

[pattismith]

some interesting datas from the study

 

[Rufous McKinney]

Large difference with irritable bowel seems of interest, but the P value was not significant, which seemed...well odd, without doing math

 

[pattismith]

Some interesting extracts from the discussion about the statistics and criteria for subgroups

Several diagnostic criteria have been proposed for use in ME/CFS, of which CCC are recommended for diagnosis confirmation in secondary care and in research. 22
Here the severity and duration of PEM is a key diagnostic criterion. In contrast to the original minimum length of 24 hours of PEM required by the CCC we set the duration criterion at 14 hours, which was shown to yield the highest diagnostic sensitivity and specificity to discriminate patients with ME/CFS from patients with fatigue due to other chronic illness. 8 12

Secondly, it is unclear, if the distinction into subgroups based on the criterion of the length of PEM indicates differences in mechanisms or merely reflect the variance of the disease spectrum.
Thirdly, the low number of patients precluded detailed comparisons of phenotypes with adequate statistical power.

In the datas I found it interesting to notice that 25% of chronic covid patients have low CD8 (I do) and 11% have low CD4.
Concerning innate immunity 22% have low MBL (I do) and 10% have low C3.

The datas says nothing about Ficolin and Ficolin autoantibodies and about B Lymphocytes subsets, I think they should be investigated in our illnesses.

The story doesn't say if there was any association between T lymphocytes imbalance and low innate immunity.

That said, I think a perfect combo to produce ME/CFS is an association of low innate immunity and any lymphocyte imbalance, and these datas confort me.

 

[pattismith]

it's difficult to compare the two studies datas.
The chronic covid one found 22% of chronic covid patients had MBL deficiency (5% in general population)
and the severe covid one (below) found 11% of infected people had homozygous variant at codon 54 (compare to 1% in healthy control);

This confirm that MBL deficiency is really a high risk factor for catching the virus and developing symptoms.

The study also suggest that the lower the MBL is, the higher the risk for severe covid or ICU admission are.

22% of severe covid patients had homozygous variant at codon 54.

50% of ICU patients had homozygous variant at codon 54.

67% of dead patients at 28 days had homozygous variant at codon 54.

Mannose binding lectin gene 2 (rs1800450) missense variant may contribute to development and severity of COVID-19 infection

2021 april
Alpay Medetalibeyoglu,a,1 Gulistan Bahat,b,⁎,1 Naci Senkal,a Murat Kose,a Kader Avci,c Gozde Yesil Sayin,d Ummuhan Isoglu-Alkac,e Tufan Tukek,a and Sacide Pehlivanc

doi: 10.1016/j.meegid.2021.104717

Abstract

Background/objectives
COVID-19 followed a mortal course in some young patients without any underlying factors, however, it followed a very benign course in some very older individuals with multiple comorbidities. These observations question if some genetic factors may be related to the vulnerability and poor prognosis of the disease. In this study, we aimed to investigate whether MBL2 gene B variant at codon 54 (rs1800450) were related to the variabilities in clinical course of this infection.

Methods
284 PCR-confirmed COVID-19 patients and 100 healthy controls were included in the study. COVID-19 patients were subdivided according to the clinical features and clinical characteristics were analyzed. DNAs of all patients and controls were examined for the codon 54 A/B (gly54asp: rs1800450) variation in exon 1 of the MBL2 gene.

Results

In univariate analysis, BB genotype of MBL2 gene was more common among COVID-19 cases compared with controls (10.9% vs 1.0%, respectively; OR = 12.1, 95%CI = 1.6–90.1, p = 0.001).

Multivariate analyses, adjusted for age, sex and MBL genetic variants, revealed that when compared with the COVID-19 patients that had AA genotype (reference),
the patients that had BB or AB genotypes suffered from a higher risk for severe disease
(for BB genotype, odds ratio (OR) = 5.3, p < 0.001; for AB genotype, OR = 2.9, p = 0.001)
and for ICU need (for BB genotype, OR = 19.6, p < 0.001; for AB genotype, OR = 6.9, p = 0.001).

On the other hand, there was not any significant difference between the genotype variants in terms of mortality at 28 days or development of secondary bacterial infection.



Discussion


Therefore, general screenings to detect MBL mutations and MBL deficiency may be used to defend against the outbreaks provided that this approach would be cost-effective.
Moreover, vaccination efforts are humbly put forward all around the World and these results may imply the selection of candidates for the vaccination with studies for confirmation of the effectiveness of vaccines in such high-risk groups.
Another point is that, as mentioned above, MBL replacement therapy, as has been used in patients with repeated infections, could have a potential for decreasing severity of or susceptibility to the disease