New preprint from Harvard & Massachusetts General Hospital -children with Long COVID show markedly increased levels of fibrinaloid microclots in their blood!
The highest levels appear in those with persistent SARS-CoV-2 spike protein in circulation🧵
The highest levels appear in those with persistent SARS-CoV-2 spike protein in circulation🧵
Long COVID affects roughly 1 in 5 children after SARS-CoV-2 infection.
Common symptoms include fatigue, brain fog, pain, and shortness of breath.
Diagnosis remains largely clinical - we still lack objective lab biomarkers for pediatric LC.
Common symptoms include fatigue, brain fog, pain, and shortness of breath.
Diagnosis remains largely clinical - we still lack objective lab biomarkers for pediatric LC.
To address this, the team led by Daniel Irimia and David Walt developed a microfluidic device that can quantifyfibrinaloid microclots - tiny, fibrin-like clots resistant to normal breakdown (fibrinolysis).
These structures can obstruct microcirculation and reduce tissue oxygen delivery.
These structures can obstruct microcirculation and reduce tissue oxygen delivery.
Participants.
45 children and young adults with Long COVID (mean 17)
14 healthy pediatric controls
Samples collected March 2023 - November 2024
= most infections occurred during the Omicron era (BA.5 - JN.1).
45 children and young adults with Long COVID (mean 17)
14 healthy pediatric controls
Samples collected March 2023 - November 2024
= most infections occurred during the Omicron era (BA.5 - JN.1).
All LC participants met CDC’s Long COVID criteria - symptoms persisting ≥3 months post infection, often lasting 6–12 months.
So - these were post-acute, not acute cases.
So - these were post-acute, not acute cases.
Results.
Long COVID 166 ± 107 microclots/sample
Healthy controls 61 ± 48
LC with detectable spike protein 229 ± 111
That’s more than a 3x increase in microclot burden in LC vs controls.
Long COVID 166 ± 107 microclots/sample
Healthy controls 61 ± 48
LC with detectable spike protein 229 ± 111
That’s more than a 3x increase in microclot burden in LC vs controls.
The new device performed remarkably well.
AUC = 0.94 (94% accuracy) at a threshold of 75 microclots/sample
Traditional manual counting under a microscope - only 66% accuracy (AUC = 0.66)
This microfluidic assay could become a screening tool for Long COVID.
AUC = 0.94 (94% accuracy) at a threshold of 75 microclots/sample
Traditional manual counting under a microscope - only 66% accuracy (AUC = 0.66)
This microfluidic assay could become a screening tool for Long COVID.
The most intriguing finding.
Children with detectable SARS-CoV-2 spike protein in plasma had the highest microclot counts.
Spike antigenemia was measured using ultrasensitive Simoa assays.
Children with detectable SARS-CoV-2 spike protein in plasma had the highest microclot counts.
Spike antigenemia was measured using ultrasensitive Simoa assays.
This test - developed by David Walt’s lab (Harvard, Wyss Institute) - can detect full-length spike protein at picogramlevels, months after infection.
It has been validated in prior studies.
It has been validated in prior studies.
Detection of spike protein months later suggests persistent viral antigen release - likely from tissue reservoirs (gut, endothelium, immune cells).
Microclot formation appears linked to this ongoing antigenemia and chronic microvascular inflammation.
Microclot formation appears linked to this ongoing antigenemia and chronic microvascular inflammation.
Importantly, the authors caution that these fibrinaloid microclots do not respond to standard anticoagulant therapy.
So their presence should not be treated as a typical clotting disorder - it reflects a distinct, pathological process of fibrin misfolding and immune activation.
So their presence should not be treated as a typical clotting disorder - it reflects a distinct, pathological process of fibrin misfolding and immune activation.
Interestingly, even LC children without detectable spike protein showed elevated microclot counts -
suggesting either intermittent antigen release below detection limits,
or that microclots can persist longer than spike itself.
suggesting either intermittent antigen release below detection limits,
or that microclots can persist longer than spike itself.
Authors conclude:
“The increased microclot burden in pediatric LC supports the role of microvascular dysfunction and persistent viral antigens in pathogenesis.”
In plain terms - pediatric Long COVID has measurable, biological signatures.
“The increased microclot burden in pediatric LC supports the role of microvascular dysfunction and persistent viral antigens in pathogenesis.”
In plain terms - pediatric Long COVID has measurable, biological signatures.
While still a preprint (not peer-reviewed), this study is important because it:
Provides a quantitative biomarker for pediatric LC,
Links microclots to persistent spike antigenemia,
Warns that these clots are anticoagulant-resistant.
Provides a quantitative biomarker for pediatric LC,
Links microclots to persistent spike antigenemia,
Warns that these clots are anticoagulant-resistant.
Pediatric Long COVID shows measurable microvascular pathology tied to persistent viral antigens -
and quantifying microclots may finally offer an objective diagnostic tool. @szupraha @ZdravkoOnline
and quantifying microclots may finally offer an objective diagnostic tool. @szupraha @ZdravkoOnline
Irimia at al., Quantification of fibrinaloid clots in plasma from pediatric Long COVID patients using a microfluidic assay. researchsquare.com/article/rs-748…
Why it matters.
Microclots are not detectable by standard lab tests (like D-dimer).
And because they don’t respond to common anticoagulants, they can easily escape clinical attention.
Without recognition, fatigue and cognitive dysfunction may persist without an obvious cause.
Microclots are not detectable by standard lab tests (like D-dimer).
And because they don’t respond to common anticoagulants, they can easily escape clinical attention.
Without recognition, fatigue and cognitive dysfunction may persist without an obvious cause.
These fibrinaloid microclots form an abnormal, amyloid-like version of fibrin.
They trap inflammatory proteins, cytokines, and complement factors -
creating a self-sustaining cycle of inflammation, microvascular obstruction, and oxidative stress.
They trap inflammatory proteins, cytokines, and complement factors -
creating a self-sustaining cycle of inflammation, microvascular obstruction, and oxidative stress.
Over time, this can impair oxygen delivery to tissues - especially the brain, heart, and muscles, where energy demand is high.
Persistent spike may maintain this process by chronically activating endothelial and immune cells = microvascular inflammation without large-vessel clots.
A silent, systemic pathology that standard medicine isn’t built to detect yet.
A silent, systemic pathology that standard medicine isn’t built to detect yet.
In children, prolonged microvascular dysfunction may carry long-term risks.
Impaired cognitive development, reduced exercise tolerance, and accelerated vascular aging.
That’s why studies like this one mark a turning point - translate invisible biology into measurable evidence.
Impaired cognitive development, reduced exercise tolerance, and accelerated vascular aging.
That’s why studies like this one mark a turning point - translate invisible biology into measurable evidence.
Public health should have an answer to this.
Children showing measurable microvascular injury and persistent viral antigens need monitoring, not dismissal.
No screening protocols, no follow-up clinics, no guidance.
Families are left to navigate a biological condition that health systems barely acknowledge. @szupraha @ZdravkoOnline @adamvojtech86
Children showing measurable microvascular injury and persistent viral antigens need monitoring, not dismissal.
No screening protocols, no follow-up clinics, no guidance.
Families are left to navigate a biological condition that health systems barely acknowledge. @szupraha @ZdravkoOnline @adamvojtech86
Yes it’s a new method, and it still needs validation.
But the biology it reveals isn’t new anymore.
Persistent spike and microvascular injury have now been shown by multiple independent teams.
What’s missing isn’t evidence - it’s acknowledgment.
But the biology it reveals isn’t new anymore.
Persistent spike and microvascular injury have now been shown by multiple independent teams.
What’s missing isn’t evidence - it’s acknowledgment.
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