TruthArchive.ai - Tweets Saved By @resiapretorius
@resiapretorius - Resia Pretorius
🧵 1/10 We are excited to share our preprint examining pre-pandemic POTS and Long COVID, using deep analysis of the insoluble microclot fraction of blood. Our study shows that the key pathology lies not in protein levels, but in post-translational modifications (PTMs) hidden within fibrinaloid microclot complexes (FMCs). With @Renata_MBooyens, Satish Raj, @dbkell and others. Funded by @POTSActivist https://www.biorxiv.org/content/10.64898/2025.12.29.696828v1.full.pdf
@resiapretorius - Resia Pretorius
🧵 2/10 Why pre-pandemic POTS matters: A unique strength of this study is the inclusion of POTS samples collected before the COVID-19 pandemic in the Raj lab. This allowed us to define the baseline molecular signature in controls and classical POTS (entirely independent of SARS-CoV-2); and to distinguish which molecular features in LC-POTS are similar to POTS biology versus acquired through Long COVID.
@resiapretorius - Resia Pretorius
🧵 3/10 What we measured: We quantified fibrinaloid microclot complexes (FMCs) using fluorescence imaging flow cytometry, then performed deep proteomics on the insoluble FMC fraction using LC-MS/MS. This allowed us to move beyond how much protein is present → to how proteins are post-translationally modified.
@resiapretorius - Resia Pretorius
🧵 4/10 Key insight: At the protein level, differences between groups were minimal. At the PTM (post-translational modification) level, differences were extensive, disease-specific, and biologically meaningful.
@resiapretorius - Resia Pretorius
🧵 5/10 Long COVID FMCs showed dominant coagulation pathology: • Extensive AGE- and oxidation-based PTMs on fibrinogen • Strong amyloidogenic signatures • Patterns resembling diabetic glycation ➡️ Consistent with microvascular damage (thrombotic endothelialitis)
@resiapretorius - Resia Pretorius
6/10 Pre-pandemic POTS showed a very different signature: • Prominent immune and complement PTMs • Oxidised apolipoproteins (apoA1, apoB) • Relatively limited fibrinogen modification ➡️ An intrinsic POTS biology, independent of SARS-CoV-2.
@resiapretorius - Resia Pretorius
🧵 7/10 Long COVID–POTS displayed a hybrid molecular phenotype: • Coagulation PTMs resembling Long COVID • Immune PTMs resembling classical POTS ➡️ Providing a molecular explanation for why LC-POTS behaves differently from either condition alone.
@resiapretorius - Resia Pretorius
🧵 8/10 Why PTMs matter: Many dysregulated peptides were highly amyloidogenic, supporting FMCs as β-sheet-rich, fibrinolysis-resistant aggregates. Crucially, these PTM signatures are invisible to standard soluble plasma assays.
@resiapretorius - Resia Pretorius
🧵 9/10 Clinical relevance: PTM profiling within FMCs opens new avenues for: • Biomarker-driven diagnosis • Patient stratification • Targeted therapies addressing glycation, oxidative stress, and complement activation This is mechanism-based medicine, not symptom-based.
@resiapretorius - Resia Pretorius
🧵 10/10 Take-home message Long COVID, POTS, and LC-POTS are biochemically distinct diseases. Their differences are encoded in post-translational modifications inside fibrinaloid microclot complexes; not in protein abundance. https://t.co/OeRL5KjRWb
