Altered amyloid plasma profile in patients with disabling headaches after SARS-CoV-2 infection and vaccination
Authors: Aamodt Anne Hege , Ueland Thor , Boldingh Marion I. , Bezgal Burcu , Argren Maria , Dunne Cecilia Adele , Otterdal Kari , Gregersen Ida , Bjerkeli Vigdis , Michelsen Annika Elisabet , Husøy Andreas , Morsund Åse Hagen , Devik Kristina , Poole Anne Christine , Gjendemsjø Kristine , Schlüter Katrin , Mathisen Sara Maria , Aalstad-Johansen Mari , Skattør Thor , Sønnervik Julie , Boye Birgitte , Popperud Trine Haug , Høgestøl Einar August , Harbo Hanne Flinstad , Lund-Johansen Fridtjof , Aukrust Pål , Tronvik Erling , Dahl Tuva Børresdatter , Halvorsen Bente E. 
Published: October 2024

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.

Conclusion

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.

NCT04576351

NCT05235776

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.