Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment

2024/02/22 by Chris Greene, Ruairi Connolly, Declan Brennan +14 · 3 voices · 13 citations
Medicine · Neuroscience · #Intensive Care Unit Cognitive Disorders #Long-Term Effects of COVID-19 #Neuroinflammation and Neurodegeneration Mechanisms

paper · pdf · doi:10.1038/s41593-024-01576-9

openalex publication_date 2024/02/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/25

Abstract

Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood-brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.

Citations

• SARS-CoV-2 is associated with changes in brain structure in UK Biobank
• A Novel Coronavirus from Patients with Pneumonia in China, 2019
• Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China
• SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
• Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study
• Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity

Cited by

• Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction
• Overview and Pathophysiology of Long COVID
• Cerebral gray matter volumes in long-term post-COVID patients are associated with peripheral kynurenine pathway metabolites and the severity of depressive symptoms
• Postural Orthostatic Tachycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroimmune Disorders
• Mechanisms of long COVID and the path toward therapeutics
• Reduced Adenosine Triphosphate-to-Phosphocreatine Ratios in Neuropsychiatric Post-COVID Condition: Evidence From 31P Magnetic Resonance Spectroscopy
• Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome
• Cognitive function and brain structure in COVID-19 survivors: The role of persistent symptoms
• Narrating the psychoneuroimmunomodulatory properties of serotonin 5-HT_2A receptor psychedelics from a transdiagnostic perspective
• Asymmetrical glymphatic dysfunction in patients with long Covid associated neurocognitive impairment- correlation with BBB disruption
• RETRACTED: Effect of subcutaneous lidocaine–hydroxypropyl-β-cyclodextrin (HP-β-CD) on quality of life in patients with post-COVID condition: a 36-week observational interrupted time series study
• Pro-resolving lipid mediators in diseases: exploring the molecular basis and clinical implication
• Blood brain barrier disruption and glutamatergic excitotoxicity in post-acute sequelae of SARS COV-2 infection cognitive impairment: potential biomarkers and a window into pathogenesis

Discussions

• Hier wurden dann «undichte» Blutgefässe im Gehirn als messbarer Mechanismus hinter dem Brain Fog bei Long COVID identifiziert. Diese Gefässpermeabilität korreliert direkt mit Gedächtnis- und Konzentra [bsky, 6 points, 1 comments]
• Bu, kan hücrelerinin beyin hücrelerine yapıştığı ve iltihaplanmaya neden olduğu anlamına geliyormuş. Bu da bazı Long Covid hastalarının muzdarip olduğu beyin sisi sorunlarının nedeni olabilirmiş. do [bsky, 1 points, 0 comments]
• Blood–brain barrier disruption and sustained systemic inflammation in individuals with #LongCovid associated #cognitive impairment. 👇 Nat Neurosci 27, 421–432 (2024). doi.org/10.1038/s415... [bsky, 0 points, 0 comments]

Related

• Cognition, Cytokines, Blood–Brain Barrier, and Beyond in COVID-19: A Narrative Review
• Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms
• A region-specific brain dysfunction underlies cognitive impairment in long COVID brain fog
• Asymmetrical glymphatic dysfunction in patients with long Covid associated neurocognitive impairment- correlation with BBB disruption
• Altered functional brain connectivity, efficiency, and information flow associated with brain fog after mild to moderate COVID-19 infection