Evidence map›Paper›PMID 42897639›Full record

ArticleCardiovascular diabetology2026

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.

Renata M Booyens, Mare Vlok, Cecile Bester, Rashmin Hira, M Asad Khan, Douglas B Kell, Satish R Raj, Etheresia Pretorius

Abstract read
In one paragraph

Article in Cardiovascular diabetology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Renata M BooyensDepartment of Physiological Sciences, Stellenbosch University, Private Bag Z1, Stellenbosch, 7599, South Africa. renatab@sun.ac.za.ORCID http://orcid.org/0009-0003-6891-0537
Mare VlokDepartment of Physiological Sciences, Stellenbosch University, Private Bag Z1, Stellenbosch, 7599, South Africa.ORCID http://orcid.org/0000-0003-2327-9449
Cecile BesterDepartment of Genetics, Stellenbosch University, Private Bag Z1, Stellenbosch, 7599, South Africa.ORCID http://orcid.org/0000-0002-9173-7248
Rashmin HiraLibin Cardiovascular Institute, University of Calgary, Calgary, CA, Canada.ORCID http://orcid.org/0009-0000-2307-3534
M Asad KhanPulmonologist and sleep physician (medically retired), Manchester, UK.ORCID http://orcid.org/0000-0003-1838-9002
Douglas B KellDepartment of Physiological Sciences, Stellenbosch University, Private Bag Z1, Stellenbosch, 7599, South Africa.ORCID http://orcid.org/0000-0001-5838-7963
Satish R RajLibin Cardiovascular Institute, University of Calgary, Calgary, CA, Canada. satish.raj@ucalgary.ca.ORCID http://orcid.org/0000-0002-5890-3785
Etheresia PretoriusDepartment of Physiological Sciences, Stellenbosch University, Private Bag Z1, Stellenbosch, 7599, South Africa. resiap@sun.ac.za.ORCID http://orcid.org/0000-0002-9108-2384

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPre-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.

methodsPlatelet-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.

resultsAlthough 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.

conclusionsThis 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.

Indexed as

Blood PlateletsCOVID-19Postural Orthostatic Tachycardia SyndromeProtein Processing, Post-TranslationalAdultBiomarkersCase-Control StudiesDiagnosis, DifferentialFemaleHumansMaleMiddle AgedPost-Acute COVID-19 SyndromePreliminary DataProteomicsBiomarkersCoagulationLong COVIDPost-translational modificationsPostural Orthostatic Tachycardia SyndromeProteomics

Identifiers

PMID42897639
PMCPMC13679111

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.