{
  "abstract": "Background\n\nPre-COVID-19 Postural Orthostatic Tachycardia Syndrome (PC-POTS), Long COVID with initial orthostatic hypotension (LC-IOH), and Long COVID-POTS (LC-POTS) are primarily chronic post-viral conditions with debilitating symptoms, despite routine laboratory findings often being normal. We previously identified amyloidogenic fibrinaloid microclot complexes (FMCs) in the insoluble fraction of platelet-poor plasma (PPP-IF) in Long COVID, but it remains unclear whether similar abnormalities occur in PC-POTS and LC-POTS, or whether post-translational modifications (PTMs) contribute to disease mechanisms.Methods\n\nPlatelet-poor plasma from healthy controls (n = 18), PC-POTS (n = 20), LC-IOH (n = 19), and LC-POTS (n = 18) participants underwent proteomic analysis of the PPP-IF using double trypsin digestion and data-independent LC-MS/MS. Differential protein abundance, PTMs, and amyloidogenicity were compared across groups.Results\n\nAlthough few proteins were significantly dysregulated, extensive disease-specific PTM alterations were identified across coagulation, immune, and metabolic pathways. LC-IOH demonstrated prominent AGE- and oxidation-related PTMs on fibrinogen subunits, particularly fibrinogen alpha chain (FIBA), resembling diabetic glycation profiles. PC-POTS showed fewer fibrinogen PTMs but marked metabolic and immune dysregulation, including oxidised apoA1 and apoB and complement-associated proteins (C3, C4A/B, IC1), IGG1, and A2MG. LC-POTS shared coagulation-related features with LC-IOH and immune-related features with PC-POTS. Many dysregulated peptides were highly amyloidogenic in silico, consistent with β-sheet-rich FMCs. PTM dysregulation was substantially greater than protein-level changes.Conclusions\n\nThis study provides the first evidence that PTMs within the PPP-IF has the potential to distinctly differentiate PC-POTS, LC-IOH, and LC-POTS. Because PC-POTS samples predated SARS-CoV-2, their PTM signatures reflect intrinsic disease biology independent of COVID-19. PTM profiling revealed pro-coagulant fibrinogen changes in LC-IOH and LC-POTS, metabolic-oxidative dysregulation in LC-IOH and PC-POTS, and immune dysregulation in PC-POTS and LC-POTS. These abnormalities were not detectable by routine assays and may contribute to microvascular dysfunction. The findings support disease-specific biomarker development and targeted therapeutic strategies across autonomic and post-viral disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physiological Sciences, Stellenbosch University, Private Bag Z1, Stellenbosch, 7599, South Africa. renatab@sun.ac.za.",
    "Department of Physiological Sciences, Stellenbosch University, Private Bag Z1, Stellenbosch, 7599, South Africa.",
    "Trace Labs, Cape Town, South Africa.",
    "Department of Genetics, Stellenbosch University, Private Bag Z1, Stellenbosch, 7599, South Africa.",
    "Libin Cardiovascular Institute, University of Calgary, Calgary, CA, Canada.",
    "Pulmonologist and sleep physician (medically retired), Manchester, UK.",
    "Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK.",
    "Libin Cardiovascular Institute, University of Calgary, Calgary, CA, Canada. satish.raj@ucalgary.ca.",
    "Department of Physiological Sciences, Stellenbosch University, Private Bag Z1, Stellenbosch, 7599, South Africa. resiap@sun.ac.za.",
    "Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK. resiap@sun.ac.za."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Renata M Booyens",
      "orcid": "0009-0003-6891-0537"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Mare Vlok",
      "orcid": "0000-0003-2327-9449"
    },
    {
      "affs": [
        3
      ],
      "name": "Cecile Bester",
      "orcid": "0000-0002-9173-7248"
    },
    {
      "affs": [
        4
      ],
      "name": "Rashmin Hira",
      "orcid": "0009-0000-2307-3534"
    },
    {
      "affs": [
        5
      ],
      "name": "M Asad Khan",
      "orcid": "0000-0003-1838-9002"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Douglas B Kell",
      "orcid": "0000-0001-5838-7963"
    },
    {
      "affs": [
        7
      ],
      "name": "Satish R Raj",
      "orcid": "0000-0002-5890-3785"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Etheresia Pretorius",
      "orcid": "0000-0002-9108-2384"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dbf86mw22npg7.bib",
  "cited_by": 0,
  "doi": "10.1186/s12933-026-03296-9",
  "fulltext_url": "https://europepmc.org/articles/PMC13679111",
  "id": "dbf86mw22npg7",
  "issns": [
    "1475-2840"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897639",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC666-701"
    ],
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      "openalex",
      "2728|Long-Term Effects of COVID-19"
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  "openalex": "W7170032698",
  "pdf_url": "https://europepmc.org/articles/PMC13679111?pdf=render",
  "pmcid": "PMC13679111",
  "pmid": "42897639",
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/dbf86mw22npg7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:42Z",
      "native_id": "MED:42897639",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897639"
    },
    {
      "first_seen": "2026-10-30T13:45:34Z",
      "native_id": "675aea29c8e34c01acb8b7ef8faa80fa",
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      "url": "https://doi.org/10.1186/s12933-026-03296-9"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Long-Term Effects of COVID-19",
      "subfield": "neurology"
    }
  ],
  "title": "Post-translational modifications in the insoluble fraction of platelet-poor plasma distinguish pre-COVID-19 Postural Orthostatic Tachycardia Syndrome, Long COVID, and Long COVID-POTS: a preliminary study.",
  "title_text": "Post-translational modifications in the insoluble fraction of platelet-poor plasma distinguish pre-COVID-19 Postural Orthostatic Tachycardia Syndrome, Long COVID, and Long COVID-POTS: a preliminary study.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:34Z",
  "url": "https://research.draconitic.com/paper/dbf86mw22npg7",
  "venue": "Cardiovascular diabetology",
  "versions": []
}