Brain Fog in Post-Covid Syndrome: Mechanisms of Microclot Formation, BBB Disruption, and Neuroinflammation

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.