{
  "abstract": "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.",
  "authors": [
    {
      "affiliations": [
        "Neurology, Oslo University Hospital, Oslo, Norway",
        "Neuroscience and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway"
      ],
      "name": "Anne Hege Aamodt"
    },
    {
      "affiliations": [
        "Research Institute of Internal Medicine and Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway",
        "Thrombosis Research Center (TREC), Division of internal medicine, University Hospital of North Norway, Tromso, Norway"
      ],
      "name": "Thor Ueland"
    },
    {
      "affiliations": [
        "Neurology, Oslo University Hospital, Oslo, Norway"
      ],
      "name": "Marion Boldingh"
    },
    {
      "affiliations": [
        "Neurology, Oslo University Hospital, Oslo, Norway",
        "Institute of Clinical Medicine, University of Oslo Faculty of Medicine, Oslo, Norway"
      ],
      "name": "Burcu Ella Bezgal"
    },
    {
      "affiliations": [
        "Neurology, Oslo University Hospital, Oslo, Norway",
        "Institute of Clinical Medicine, University of Oslo Faculty of Medicine, Oslo, Norway"
      ],
      "name": "Maria Bengtson Argren"
    },
    {
      "affiliations": [
        "Institute of Clinical Medicine, University of Oslo Faculty of Medicine, Oslo, Norway"
      ],
      "name": "Cecilia Adele Dunne"
    },
    {
      "affiliations": [
        "Neurology, Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway"
      ],
      "name": "Kari Otterdal"
    },
    {
      "affiliations": [
        "Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway"
      ],
      "name": "Ida Gregersen"
    },
    {
      "affiliations": [
        "Institute of Clinical Medicine, University of Oslo Faculty of Medicine, Oslo, Norway",
        "Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway"
      ],
      "name": "Vigdis Bjerkeli"
    },
    {
      "affiliations": [
        "Institute of Clinical Medicine, University of Oslo Faculty of Medicine, Oslo, Norway",
        "Neurology, Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway"
      ],
      "name": "Annika Elisabet Michelsen"
    },
    {
      "affiliations": [
        "Neuroscience and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway",
        "Department of Neurology, St Olavs Hospital Trondheim University Hospital Neurology Clinic, Trondheim, Norway"
      ],
      "name": "Andreas Husøy"
    },
    {
      "affiliations": [
        "Department of Neurology, Helse More og Romsdal HF, Alesund, Norway"
      ],
      "name": "Åse Hagen Morsund"
    },
    {
      "affiliations": [
        "Neurology, Namsos Hospital, Namsos, Norway",
        "Department of Neuromedicine and Movement Science, Norges teknisk-naturvitenskapelige universitet, Trondheim, Norway"
      ],
      "name": "Kristina Devik"
    },
    {
      "affiliations": [
        "Oslo Headache Centre, Oslo, Norway"
      ],
      "name": "Anne Christine Poole"
    },
    {
      "affiliations": [
        "Sandvika Neuro Centre, Oslo, Norway"
      ],
      "name": "Kristine Bodding Gjendemsjø"
    },
    {
      "affiliations": [
        "Stavanger University Hospital, Stavanger, Norway"
      ],
      "name": "Katrin Schlüter"
    },
    {
      "affiliations": [
        "Stavanger University Hospital, Stavanger, Norway"
      ],
      "name": "Sara Maria Mathisen"
    },
    {
      "affiliations": [
        "Neurology, Sykehuset Innlandet HF Divisjon Lillehammer, Lillehammer, Norway"
      ],
      "name": "Mari Aalstad-Johansen"
    },
    {
      "affiliations": [
        "Institute of Clinical Medicine, University of Oslo Faculty of Medicine, Oslo, Norway",
        "Radiology, Oslo University Hospital, Oslo, Norway"
      ],
      "name": "Thor Håkon Skattør"
    },
    {
      "affiliations": [
        "Hodeverket, Sandnes, Norway"
      ],
      "name": "Julie Sønnervik"
    },
    {
      "affiliations": [
        "Institute of Basic Medical Sciences, University of Oslo Faculty of Medicine, Oslo, Norway",
        "Unit Psychosomatic Medicine and CL Psychiatry, Oslo universitetssykehus, Oslo, Norway"
      ],
      "name": "Turid Birgitte Boye"
    },
    {
      "affiliations": [
        "Neurology, Oslo University Hospital, Oslo, Norway"
      ],
      "name": "Trine Haug Popperud"
    },
    {
      "affiliations": [
        "Neurology, Oslo University Hospital, Oslo, Norway",
        "Institute of Clinical Medicine, University of Oslo Faculty of Medicine, Oslo, Norway"
      ],
      "name": "Einar August Høgestøl"
    },
    {
      "affiliations": [
        "Neurology, Oslo University Hospital, Oslo, Norway",
        "Institute of Clinical Medicine, University of Oslo Faculty of Medicine, Oslo, Norway"
      ],
      "name": "Hanne Flinstad Harbo"
    },
    {
      "affiliations": [
        "Institute of Clinical Medicine, University of Oslo Faculty of Medicine, Oslo, Norway",
        "Immunology, Oslo University Hospital, Oslo, Norway"
      ],
      "name": "Fridtjof Lund-Johansen"
    },
    {
      "affiliations": [
        "Institute of Clinical Medicine, University of Oslo Faculty of Medicine, Oslo, Norway",
        "Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway"
      ],
      "name": "Pål Aukrust"
    },
    {
      "affiliations": [
        "Neuroscience and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway",
        "Department of Neurology, St Olavs Hospital Trondheim University Hospital Neurology Clinic, Trondheim, Norway"
      ],
      "name": "Erling Tronvik"
    },
    {
      "affiliations": [
        "Neurology, Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway"
      ],
      "name": "Tuva Børresdatter Dahl"
    },
    {
      "affiliations": [
        "Institute of Clinical Medicine, University of Oslo Faculty of Medicine, Oslo, Norway",
        "Research Institute for Internal Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway",
        "Department of Medicine, Division of Cardiovascular Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, USA"
      ],
      "name": "Bente Evy Halvorsen"
    }
  ],
  "title": "Altered amyloid plasma profile in patients with disabling headaches after SARS-CoV-2 infection and vaccination",
  "uid": "26115172-e4f9-5fa7-a6c8-160adb9d4572"
}