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
Authors' conclusion
This study provides the first evidence that PTMs within the PPP-IF has the potential to distinctly differentiate PC-POTS, LC-IOH, and LC-POTS.
Study context
- Population
- Participants with PC-POTS, Long COVID with initial orthostatic hypotension (LC-IOH) or Long COVID-POTS (LC-POTS) and healthy controls; proteomic analysis of the insoluble fraction of platelet-poor plasma (PPP-IF)
- Participants
- 18 / 20 / 19 / 18
- Exposure
- PC-POTS vs LC-IOH vs LC-POTS vs healthy controls
- Healthy controlsn = 18reference
- PC-POTSn = 20
- LC-IOHn = 19
- LC-POTSn = 18
- Outcome
- Differential protein abundance, PTMs and amyloidogenicity in PPP-IF
Methodological detailspreliminary study, double trypsin digestion, data-independent LC-MS/MS
- Preliminary study
- Double trypsin digestion
- Data-independent LC-MS/MS
Main finding
As reported in the abstract
- Few proteins significantly dysregulated, but extensive disease-specific PTM alterations across coagulation, immune and metabolic pathways
- LC-IOH: prominent AGE- and oxidation-related post-translational modifications (PTMs) on fibrinogen subunits, particularly FIBA, resembling diabetic glycation profiles
- PC-POTS: fewer fibrinogen PTMs but marked metabolic and immune dysregulation, incl. oxidised apoA1 and apoB, 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 highly amyloidogenic in silico, consistent with β-sheet-rich fibrinaloid microclot complexes (FMCs)
- PTM dysregulation substantially greater than protein-level changes
Observational data: associations, not effects.
Original publication
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. Cardiovasc Diabetol. Published 23 July 2026. doi:10.
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