ArticleFrontiers in immunology2022
Markers of blood-brain barrier disruption increase early and persistently in COVID-19 patients with neurological manifestations.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.
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Who cites it
56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- Systematic review and evidence gap mapping of biomarkers associated with neurological manifestations in patients with COVID-19.Journal of neurology · 2024Pooled it
- Blood Biomarkers as Prognostic Indicators for Neurological Injury in COVID-19 Patients: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2023Pooled it
- Human brain matters: Navigating the neuropathology of COVID-19.Brain pathology (Zurich, Switzerland) · 2026Review
- Blood-Brain Barrier Changes and Related Microvascular Outcomes in Long-COVID: A Comprehensive Review.Life (Basel, Switzerland) · 2026Review
- Proteomic analysis reveals divergent inflammatory mechanisms of COVID-associated Guillain-Barré syndrome.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Resting-state functional connectivity and cognitive impairment after COVID-19 infection: Evidence from a large-scale fMRI study.European psychiatry : the journal of the Association of European Psychiatrists · 2026Article
- Long COVID-associated neurological symptoms and brain fog: Understanding the mechanism of neuroinflammation, BBB disruption, diagnostics, and therapeutics.Molecular biology reports · 2026Review
- Tau is necessary for Pseudomonas aeruginosa-induced blood-brain barrier dysfunction.Communications biology · 2026Article
- Dysregulation of MMP-2 and MMP-9 in Post-COVID-19 and IPF: Correlations with Systemic Inflammation and Endothelial Dysfunction.Journal of clinical medicine · 2026Article
- Cognition, Cytokines, Blood-Brain Barrier, and Beyond in COVID-19: A Narrative Review.International journal of molecular sciences · 2026Review
- Lingering echoes of SARS-CoV-2: mechanistic insights and management of long COVID syndrome.Inflammopharmacology · 2026Review
- Immune effector cell-associated neurotoxicity syndrome following CAR T-cell therapy: a review of recent advances.Journal of translational medicine · 2025Review
- Involvement of oxidative stress in post-acute sequelae of COVID-19: clinical implications.Redox report : communications in free radical research · 2025Article
- Article
- Acute haemorrhagic necrotizing encephalopathy and inflammatory demyelinating encephalopathy associated with COVID-19 in adults in Southern China.BMC infectious diseases · 2025Article
- Immunomodulatory Mechanisms Underlying Neurological Manifestations in Long COVID: Implications for Immune-Mediated Neurodegeneration.International journal of molecular sciences · 2025Review
- Review
- Observational
- Biomarkers of blood-brain barrier and neurovascular unit integrity in human cognitive impairment and dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health.GeroScience · 2025Review
Corrections and comments
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Authors and funding
29 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is associated with disorders affecting the peripheral and the central nervous system. A high number of patients develop post-COVID-19 syndrome with the persistence of a large spectrum of symptoms, including neurological, beyond 4 weeks after infection. Several potential mechanisms in the acute phase have been hypothesized, including damage of the blood-brain-barrier (BBB). We tested weather markers of BBB damage in association with markers of brain injury and systemic inflammation may help in identifying a blood signature for disease severity and neurological complications. Methods: Blood biomarkers of BBB disruption (MMP-9, GFAP), neuronal damage (NFL) and systemic inflammation (PPIA, IL-10, TNFα) were measured in two COVID-19 patient cohorts with high disease severity (ICUCovid; n=79) and with neurological complications (NeuroCovid; n=78), and in two control groups free from COVID-19 history, healthy subjects (n=20) and patients with amyotrophic lateral sclerosis (ALS; n=51). Samples from COVID-19 patients were collected during the first and the second wave of COVID-19 pandemic in Lombardy, Italy. Evaluations were done at acute and chronic phases of the COVID-19 infection. Results: Blood biomarkers of BBB disruption and neuronal damage are high in COVID-19 patients with levels similar to or higher than ALS. NeuroCovid patients display lower levels of the cytokine storm inducer PPIA but higher levels of MMP-9 than ICUCovid patients. There was evidence of different temporal dynamics in ICUCovid compared to NeuroCovid patients with PPIA and IL-10 showing the highest levels in ICUCovid patients at acute phase. On the contrary, MMP-9 was higher at acute phase in NeuroCovid patients, with a severity dependency in the long-term. We also found a clear severity dependency of NFL and GFAP levels, with deceased patients showing the highest levels. Discussion: The overall picture points to an increased risk for neurological complications in association with high levels of biomarkers of BBB disruption. Our observations may provide hints for therapeutic approaches mitigating BBB disruption to reduce the neurological damage in the acute phase and potential dysfunction in the long-term.
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Registered trials
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