[Case Report] Circulating microaggregates as biomarkers for the Post‐COVID syndrome, 2024, Hermann et al.

SNT Gatchaman

SNT Gatchaman

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Circulating microaggregates as biomarkers for the Post‐COVID syndrome
Hermann; Lisch; Gerth; Wick; Fries; Wick

CoVID-19 can develop into Post-COVID syndrome of potentially high morbidity, with procoagulation and reactivation of dormant viral infections being hypothesized pathophysiological mechanisms. We report on a patient suffering from fatigue, post exertional malaise, pain and neurological symptoms as a consequence of the second CoVID infection.

Using live confocal microscopy on native whole blood samples we detected microaggregates of thrombocytes, leukocytes and plasma proteins in peripheral blood. In addition, there was specific cellular immunological reactivity to EBV. Upon anticoagulatory and virustatic pharmacological therapy we observed dissolution of microaggregates and significant stable clinical remission.

We suggest to consider circulating microaggregates as a morphological indicator of chronic post-COVID syndrome.

Link | PDF (IDCases)
 
In order to evaluate the presence of microaggregates in circulating blood with potential rheological consequences, we applied real time live confocal microscopy on native whole blood samples (Fig. 1) [2]. We detected formation of globular microaggregates measuring 100 µm in diameter in average consisting of cellular and acellular plasmatic components. Besides thrombocytes, cells in close proximity to the microaggregates were identified as mononuclear and polymorphonuclear leukocytes. There was a variable degree of cell lysis around a core of glycoproteins that were labeled with wheat germ agglutinin. Parallel thrombocytic function analysis pointed towards an increased platelet aggregation (data not shown).
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Screen Shot 2024-06-05 at 5.37.16 am.png
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That's Figure 1. Top row is before treatment; bottom row is after treatment
The left panel shows DNA. They say the small blue dots are the mitochondria in the thrombocytes (platelets) which are clustered with some white blood cells (larger blue shapes). The middle red panel is
wheat germ agglutinin (WGA) detects N-acetyl-d-glucosamine and N-acetyl-d-neuraminic acid residues on the surface of erythrocytes and within precipitates of proteins.
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The right panel is just the two other images overlaid on each other.
 
I don't know what to make of this, other than, of course, it's a case study of one case from a clinic, and so suggestions of recovery could very easily not mean a lot. People often do recover from Post-Covid syndrome. The paper doesn't tell us how long the woman had been sick before starting treatment.

Also, the paper serves as an advertisement for the clinic. Maybe our Austrian members know the authors?
The case reported is a patient under therapy at private practices of Dr. Lisch and Dr. Wick.
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I didn't see any indication of the number of these aggregates found before treatment started.
There's also quite a lot of things thrown into the mix e.g.
While anti-EBV antibodies were negative, there was a significant elevation of specific T cells reacting against EBV peptides.
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Indirect immunofluorescence on mouse tissue showed weak reactivity of bona fide autoantibodies against autonomic myenteric nerves (data not shown).
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(myenteric = nerves situated between and supplying the two layers of muscle in the small intestine.)


The patient received enoxaparin 1 × 40 mg daily plus 100 mg acetylsalicylic acid twice daily in parallel to gastric protection with famotidine for four weeks. We observed stable 50 % improvement of sleep disorders, pain, fatigue, neurological symptoms including autonomous disorders, and post exertional malaise. In a secondary approach, we added 1,000 mg valaciclovir three times per day, which led to a further reduction of fatigue symptoms. Overall, Bell Score 1995 increased from 40 to 90 with further improvement until present. After completion of this treatment cycle, we again imaged the blood viareal time live confocal microscopy and did not find any microaggregates.
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I am doubtful that the valacyclovir did anything useful - other studies with it have not found any benefit. 'Secondary Hypogonadism' is mentioned as a symptom, which I assume is low oestrogen. There's no report on whether the 'secondary hypogonadism' resolved with the resolution of other symptoms. There's no report of how many months it has been since the 90 Bell score.

I do agree that looking at the blood carefully is a good idea and more of that should be done. While admittedly I would be skeptical of any case study report from a private clinic, there is quite a lot of information missing that would have made the case study more compelling. In addition to the missing information I have already noted, are the clinicians finding their treatment regime is useful in other patients, or is this the first patient they have applied it to? Have they found the microaggregates in other patients?
 
Hutan said:
They say the small blue dots are the mitochondria in the thrombocytes (platelets) which are clustered with some white blood cells (larger blue shapes).
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There is no way this would have existed in the patient, other than maybe on the edge of the needle where a thrombus had formed during rather slow blood taking. The sample was presumably venous blood. If a lump like that was in venous blood it would get filtered out in the pulmonary microvessels anyway. But I think it would be pretty impossible for that number of neutrophils to congregate around some platelet garbage in the time it takes for blood to flow in a vein.

We have already seen stuff that really makes no sense in this area. The standard of peer review is now so low that just about anything gets published.
 
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