Altered amyloid plasma profile in patients with disabling headaches after SARS-CoV-2 infection and vaccination, 2025, Aamodt et al.

[SNT Gatchaman]

Now published, see post #6
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Altered amyloid plasma profile in patients with disabling headaches after SARS-CoV-2 infection and vaccination
Anne Hege Aamodt; Thor Ueland; Marion Boldingh; Burcu Ella Bezgal; Mari Argren; Cecilia Adele Dunne; Kari Otterdal; Ida Gregersen; Vigdis Bjerkeli; Annika Elisabet Michelsen; Andreas Husoey; Aase Hagen Morsund; Kristina Devik; Anne Christine Poole; Kristine Bodding Gjendemsjoe; Katrin Schluter; Sara Maria Mathisen; Mari Aalstad-Johansen; Thor Haakon Skattoer; Julie Soennervik; Turid Birgitte Boye; Trine Haug Popperud; Einar August Hoegestoel; Fridtjof Lund-Johansen; Paal Aukrust; Erling Tronvik; Tuva Boerresdatter Dahl; Bente Halvorsen

BACKGROUND AND OBJECTIVES
New onset persistent headache has been reported following acute COVID-19 disease and to some degree also after SARS-CoV-2 vaccination. Still, the mechanisms for these headache types are unclear. The purpose of this study was to assess levels of amyloid related biomarkers in patients with persistent headache after COVID-19 and SARS-CoV-2 vaccine.

METHODS
In this prospective observational cohort, patients with severe headache as the dominating symptom after COVID-19 disease (n=29) and SARS-CoV-2 vaccination (n=31), had neurological assessments with reassessments after 6 months. Plasma levels of amyloid precursor protein (APP), pregnancy zone protein (PZP), cathepsin L1 (CTSL) and serum Amyloid A (SAA1) were measured by ELISA in relation to levels in healthy controls (n=16).

RESULTS
We found a strong and persistent upregulation of APP in patients with headache after COVID-19 as compared to the two other groups. At both inclusion and after 6 months APP levels were also increased in those with accompanying cognitive symptoms. In contrast, plasma levels of PZP were elevated in both headache groups as compared to healthy controls at inclusion and after 6 months follow-up, but with no relation to cognitive symptoms. CTSL was only elevated in those with COVID-19 associated headache at baseline, whereas SAA1 showed levels comparable in all groups.

CONCLUSIONS
Altered plasma levels of soluble markers potentially reflecting changes in amyloid processing was found in patients with persistent headache after SARS-CoV-2 vaccine and particular in those with persistent headache after COVID-19 disease where we also found some association with cognitive symptoms.


Link | PDF (Preprint: MedRxiv) [Open Access]

 

[SNT Gatchaman]

What is already known on this topic
New onset persistent headache occurs in a subset of individuals after COVID-19 and to some extent after SARS-CoV-2 vaccine. However, the pathophysiological mechanisms are unknown.

What this study adds
There was high disability with only modest improvement after 6-month follow-up.

Altered plasma levels of soluble markers that potentially could reflect changes in amyloid processing was found in patients with persistent headache after SARS-CoV-2 vaccine and particular in those with persistent headache after COVID-19 disease with association to cognitive symptoms.

How this study might affect research, practice or policy
Our data point to plausible mechanism of amyloid processing and neuroinflammation in relation to COVID-19 and SARS-CoV-2 vaccine.

 

[SNT Gatchaman]

Exclusion criteria were shortlasting headaches, no follow-up assessments, or where other diagnoses were considered a better explanation for their symptoms (e.g. infections including COVID-19, head trauma, or somatoform disorders).

!!

(Remember kids, the first rule of somatoform disorders is never biologically investigate.)

 

[SNT Gatchaman]

 

[Sean]

(Remember kids, the first rule of somatoform disorders is never biologically investigate.)

Second Rule: If an association with a biological variable becomes undeniable, then make sure the direction of causation is always assumed to be psyche–>soma.

 

[SNT Gatchaman]

Now published —

Altered amyloid plasma profile in patients with disabling headaches after SARS-CoV-2 infection and vaccination

Spoiler: Authors

Anne Hege Aamodt; Thor Ueland; Marion Boldingh; Burcu Ella Bezgal; Maria Bengtson Argren; Cecilia Adele Dunne; Kari Otterdal; Ida Gregersen; Vigdis Bjerkeli; Annika Elisabet Michelsen; Andreas Husøy; Åse Hagen Morsund; Kristina Devik; Anne Christine Poole; Kristine Bodding Gjendemsjø; Katrin Schlüter; Sara Maria Mathisen; Mari Aalstad-Johansen; Thor Håkon Skattør; Julie Sønnervik; Turid Birgitte Boye; Trine Haug Popperud; Einar August Høgestøl; Hanne Flinstad Harbo; Fridtjof Lund-Johansen; Pål Aukrust; Erling Tronvik; Tuva Børresdatter Dahl; Bente Evy Halvorsen

BACKGROUND AND OBJECTIVES
Persistent headache has emerged as a symptom following acute COVID-19 and, to a lesser extent, after SARS-CoV-2 vaccination. However, the underlying mechanisms remain poorly understood. This study aimed to evaluate plasma levels of amyloid-related biomarkers in patients experiencing persistent headaches after COVID-19 or SARS-CoV-2 vaccination.

METHODS
In this prospective observational cohort, patients presenting with severe headache as the dominating symptom after COVID-19 (n=29) or SARS-CoV-2 vaccination (n=31) had neurological assessments with reassessments after 6 months. Plasma levels of amyloid precursor protein (APP), pregnancy zone protein (PZP), cathepsin L1 (CTSL) and serum Amyloid A (SAA1) were measured using ELISA and compared with levels in healthy controls (n=16).

RESULTS
We found a strong and persistent upregulation of APP in patients with headache after COVID-19 as compared with the two other groups. Notably, APP levels remained elevated at both inclusion and after 6 months in individuals with accompanying cognitive symptoms. In contrast, PZP levels were increased in patients with headache after SARS-CoV-2 vaccination at both time points relative to healthy controls. CTSL was only elevated in the post-COVID-19 at baseline, whereas SAA1 showed levels comparable across all groups.

CONCLUSION
Altered plasma levels of soluble markers, potentially reflecting changes in amyloid processing, were found in patients with persistent headache following SARS-CoV-2 vaccine, particularly in those with persistent headache after COVID-19. In the latter group, we also found some association with cognitive symptoms.

TRIAL REGISTRATION NUMBERS
NCT04576351 and NCT05235776.

Web | PDF | BMJ Neurology Open | Open Access

 

[Ryan31337]

This one is all too relevant to me, unfortunately. Diagnosed chronic migraine and probable SUNCT (a trigeminal autonomic cephalalgia), which developed in the past couple of years.

I wonder how many of those deemed to have "cranial neuralgia" in this study were a missed SUNCT diagnosis, rather than something classic like trigeminal neuralgia.