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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · 3d

We already knew that severe acute #COVID19 is induced by pathogenic IgG. But now Lynn Mes & @oliverch77.bsky.social show in @eurjimmunol.bsky.social that IgA2 adds even more fuel to the fire 🔥: onlinelibrary.wiley.com/doi/10.1002/...

Anti‐SARS‐CoV‐2 Spike IgA2 Induces Inflammation by Human Macrophages

Anti-SARS-CoV-2 spike IgA drives inflammation in human macrophages through FcαRI-Syk signaling. IgA2 immune complexes amplify cytokine production and alter glycolysis and mitochondrial function more ....

onlinelibrary.wiley.com

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 30

Taken together, both “ends” of the antibody response appear affected in Long COVID:
– the antigen binding part (Fab)
– the tail (Fc)
This may not only impede SARS-CoV-2 clearance, but also hint at broader immune dysfunction.

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 30

🔹 Aberration 2: Impaired class switching.
Normally, B cells switch from IgM to potent, long-lasting IgG.
In Long COVID, this switch is blunted — reducing the production of high-affinity IgG needed for viral clearance.

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 30

🔹 Aberration 1: Immunological imprinting (“original antigenic sin”).
Instead of mounting fresh responses to SARS-CoV-2, B cells fall back on memory from seasonal coronaviruses. The result: antibodies less effective against the new virus.

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 30

The results:
– Reduced SARS-CoV-2 spike-specific IgG and IgA
– Elevated IgG against spike of seasonal coronaviruses
This points to two distinct immunological abnormalities 👇

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 30

Aberrant immune responses have long been suspected to play a role in #LongCOVID.
Here, we examined antibody profiles against both SARS-CoV-2 and the “everyday” seasonal coronaviruses. 2/6

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 30

Long COVID patients show immunological imprinting and impaired antibody class switching: fewer IgG/IgA antibodies against SARS-CoV-2 spike, but more against seasonal coronaviruses.
Interesting finding by my PhD student Ashwin Mak in J Med Virol: onlinelibrary.wiley.com/doi/10.1002/... 1/6

Seasonal Coronavirus‐Induced Immunological Imprinting and Previous Herpesvirus Infections in Patients With Long COVID

Long COVID (LC) is a post-acute infection syndrome affecting 5%–10% of individuals infected by SARS-CoV-2. Here, we aimed to study SARS-CoV-2 humoral immunity, immunological imprinting by endemic cor...

onlinelibrary.wiley.com

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 13

Also pretty proud of my team Oliver Chen, Amélie Bos, and Ashwin Mak (2 oral presentations, 3 posters) that resp. showed that Long COVID autoantibodies remain pathogenic for years, can directly affect skeletal muscle cells, and that patients show impaired antibody isotype switching. 7/

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 13

@virusesimmunity.bsky.social showed that IgG of Long COVID patients that is transferred to mice partially ends up in the brain, indicating that these IgGs may disrupt the blood-brain barrier. Could be an important step in the development of neurological symptoms. 6/

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 13

Maureen Hansen presented her recently published work on identification of circulating cell-free RNA signatures for the characterization and diagnosis of ME/CFS: www.pnas.org/doi/10.1073/... 5/

Circulating cell-free RNA signatures for the characterization and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome | PNAS

People living with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience heterogeneous and debilitating symptoms that lack suffici...

www.pnas.org

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 13

Esther Melamed showed that 25% of the patients in their (large) cohort display anti-ganglioside antibodies (not included in most autoantibody arrays): www.medrxiv.org/content/10.1... Let’s all check this in our cohorts! 4/

Analysis of 977 Long COVID Patients Reveals Prevalent Neuropathy and Association with Anti-Ganglioside Antibodies

Background Long COVID (LC) is a novel condition that is characterized by persistent symptoms that last from months to years following a SARS-CoV-2 infection. While LC symptoms vary widely, neuropathy ...

www.medrxiv.org

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 13

In vivo models: more and more mouse models are being developed to study pathophysiology and therapies. Nadia Roan showed that machine learning is a promising strategy to boost the quality of Long COVID models, and (successfully) test therapies. 3/

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 13

First, a call to action from @virusesimmunity.bsky.social to combine all our data internationally. Maureen Hansen mentioned that such a repository website already exists for #MECFS MAPMECFS.org. Could we make this for Long COVID as well? 2/

Welcome - mapMECFS

MAPMECFS.org

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Aug 13

Big thanks to @keystonesymposia.bsky.social @virusesimmunity.bsky.social @ahandvanish.bsky.social @daltmann.bsky.social and others for organization of the second #LongCOVID Keystone #KSLongCOVID26. I’ll mention a few personal highlights. 1/

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Jul 17

Huge congratulations to my talented postdoc @oliverch77.bsky.social on obtaining the prestigious Veni grant! On your way to start your own research group 🙂. www.zonmw.nl/en/news/200-...

200 researchers receive Veni grants | 31 ZonMw projects

Improving the quality of surgery with video analysis. The crosstalk between sodium homeostasis and the gut microbiome. Can nature's microbes keep allergies away

www.zonmw.nl

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Jun 25

Finally, big thanks to the involved doctors Thadé Goderie, Niek Versfeld, and Alain Bauwens. And to Noaharu Kitajima, who previously described post-acute infection dizziness like this after influenza: pubmed.ncbi.nlm.nih.gov/27089972/ 10/10

pubmed.ncbi.nlm.nih.gov

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Jun 25

So if dizziness is your ONLY post-COVID symptom, you could ask your GP to check your eardrum during nasal respiration. If it moves, placing a ventilation tube may work. If afterwards your eye muscles become painful, vestibulo-visual rehabilitation may work. 9/10

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Jun 25

The good news is that vestibular asthenopia (tired and painful eyes, difficulty “scrolling” on screens) can also be fixed, by specialized vestibulo-visual rehabilitation. Which involves a rotating chair and weird 3D patterns…: 8/10

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Jun 25

Yet, during these 6 months, the brain started “ignoring” the vestibular system, and learned to only rely on the eyes for balance. As soon as the vestibular system worked again, this caused something known as “vestibular asthenopia”: pubmed.ncbi.nlm.nih.gov/34556339/ 7/10

Vestibular asthenopia - PubMed

Vestibular asthenopia, analogous to visual asthenopia, is a sensory (or sensory-motor) discomfort consisting of a set of subjective symptoms, the expression of which is essentially visual and whose or...

pubmed.ncbi.nlm.nih.gov

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Jun 25

The treatment was remarkably simple: placing a ventilation tube, to counteract the movement of the eardrum. After 6 months, the dizziness instantly disappeared. 6/10

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Jun 25

In this particular patient (me), dizziness only occurred during breathing. It turned out that the “open” eustachian tube made the eardrum move, triggering the inner ear (vestibular system), causing dizziness. 5/10

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Jun 25

The eustachian tube is a connection between your nose and ear. It is typically closed, and only opens briefly to equalize pressure (e.g. when you’re flying). But sometimes it stays open: a patulous eustachian tube. 4/10

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Jun 25

Quick summary: COVID-19 can cause dizziness by triggering a “patulous eustachian tube”, which can be fixed by placing a ventilation tube in your eardrum. Wait, a patulous what…? 3/10

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Jun 25

Disclaimer: we think that cases like this are rare. Yet, if you do suffer from this, the good news is that the cause of dizziness could be easily fixed by an ear nose and throat doctor (and some specialized vestibular physiotherapy). 2/10

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Dr. Jeroen den Dunnen @drdendunnen.bsky.social · Jun 25

For people that suffer from post-COVID-19 dizziness (as their ONLY symptom), this case report may be of interest to you: casereports.bmj.com/content/18/6.... A tale from personal experience… 1/10

casereports.bmj.com

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