BRAIN FOG IN POST-COVID SYNDROME: MECHANISMS OF MICROCLOT FORMATION, BBB DISRUPTION, AND NEUROINFLAMMATION

Szymon Skrzypek; Natalia Skórka; Bartosz Wójtowicz; Jakub Jasionka; Karolina Skórka; Oliwia Żmuda; Weronika Skrzypek; Magdalena Chrościńska-Krawczyk

doi:10.31435/ijitss.3(51).2026.5902

Authors

Szymon Skrzypek Student Scientific Club of Pediatric Neurology, Medical University of Lublin, Lublin, Poland https://orcid.org/0009-0009-9174-7786
Natalia Skórka Student Scientific Club of Pediatric Neurology, Medical University of Lublin, Lublin, Poland https://orcid.org/0009-0008-7336-9569
Bartosz Wójtowicz Student Scientific Club of Pediatric Neurology, Medical University of Lublin, Lublin, Poland https://orcid.org/0000-0002-7396-9117
Jakub Jasionka Student Scientific Club of Pediatric Neurology, Medical University of Lublin, Lublin, Poland https://orcid.org/0009-0003-7359-5199
Karolina Skórka Student Scientific Club of Pediatric Neurology, Medical University of Lublin, Lublin, Poland https://orcid.org/0009-0003-1523-925X
Oliwia Żmuda Student Scientific Club of Pediatric Neurology, Medical University of Lublin, Lublin, Poland https://orcid.org/0009-0005-0415-786X
Weronika Skrzypek 1st Military Clinical Hospital with the Outpatient Clinic, Lublin, Poland https://orcid.org/0009-0004-3353-1390
Magdalena Chrościńska-Krawczyk dr hab. n. med., Department of Child Neurology, Medical University of Lublin, Chodzki 2, 20-093 Lublin, Poland https://orcid.org/0000-0001-8121-6580

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.5902

Keywords:

Post-COVID Syndrome; Brain Fog; Blood-Brain Barrier; Neuroinflammation; Microclots; Fibrin Amyloid

Abstract

Background: Post-COVID syndrome (PCS) is characterized by persistent symptoms following infection, most notably "brain fog." Affecting approximately 5-15% of individuals in recent vaccinated cohorts-and up to 30% in early pandemic studies-brain fog significantly impairs professional, educational, and daily functioning. Its underlying biological mechanisms remain unclear, partly due to heterogeneous case definitions and study designs.

Methods: We conducted a narrative, hypothesis-driven review of PubMed, Web of Science and Scopus from 2019 to January 2026, focusing on human mechanistic studies of PCS-related cognitive dysfunction.

Findings: Several human cohorts describe persistence of SARS-CoV-2 spike antigen in plasma months after infection. Studies associate this with three overlapping pathways: (1) formation of fibrin amyloid microclots with impaired fibrinolysis in vitro; (2) increased blood-brain barrier permeability linked to elevated MMP-9 and oxidative stress markers in blood and CSF; and (3) sustained microglial and astrocytic reactivity with elevated cytokines. Evidence is largely cross-sectional and mechanistic data derive mostly from small studies. The specificity and causal role of microclots in post-COVID syndrome remain contested in recent reviews.

Interpretation: We outline a testable integrative model in which microvascular injury, blood-brain barrier disruption and neuroinflammation may contribute to persistent cognitive symptoms in PCS. The model remains hypothetical, as current data are largely cross-sectional and derive partly from in vitro work. Longitudinal studies with biomarker stratification are needed before mechanism-based interventions can be evaluated.

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