The Molecular Mechanisms of Cognitive Dysfunction in Long COVID: A Narrative Review DOI Open Access
Elena Popa, Andrei Emilian Popa,

Mihaela Poroch

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(11), С. 5102 - 5102

Опубликована: Май 26, 2025

Cognitive dysfunction represents one of the most persistent and disabling features Long COVID, yet its molecular underpinnings remain incompletely understood. This narrative review synthesizes current evidence on pathophysiological mechanisms linking SARS-CoV-2 infection to long-term neurocognitive sequelae. Key processes include neuroinflammation, blood–brain barrier (BBB) disruption, endothelial dysfunction, immune dysregulation, neuroendocrine imbalance. Microglial activation cytokine release (e.g., IL-6, TNF-α) promote synaptic neuronal injury, while inflammasomes such as NLRP3 amplifies CNS inflammation. Vascular abnormalities, including microthrombosis BBB leakage, facilitate infiltration peripheral cells neurotoxic mediators. Hypothalamic–pituitary–adrenal axis reduced vagal tone further exacerbate systemic inflammation autonomic Biomarkers GFAP, NFL, S100B have been associated with both neuroinflammation cognitive symptoms. Notably, transcriptomic signatures in COVID overlap those observed Alzheimer’s disease, highlighting shared pathways involving tau oxidative stress, glial reactivity. Understanding these is critical for identifying at-risk individuals developing targeted therapeutic strategies. underscores need longitudinal research integrative biomarker analysis elucidate trajectory impairment COVID.

Язык: Английский

Investigating the Neuroimmune, Cerebrovascular, and Cognitive Disturbances Associated with SARS‑CoV‑2 Infection: A Systematic Review of Post‑Acute Outcomes DOI Creative Commons

Hnin Aung

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Abstract Background SARS-CoV-2, initially identified as a respiratory pathogen, has emerged significant driver of neurological morbidity in the post-acute phase infection. A substantial body evidence now underscores persistent neuroimmune dysregulation, cerebrovascular injury, and cognitive impairment critical contributors to long-term disability among COVID-19 survivors. However, mechanistic interplay between these processes their clinical implications remains incompletely characterized. Objectives This systematic review synthesizes global (1) elucidate pathophysiological mechanisms underlying sequelae COVID-19, (2) evaluate prevalence spectrum neuroimmune, cerebrovascular, disturbances, (3) propose actionable strategies for management future research. Methods comprehensive search PubMed, EMBASE, Cochrane Library was conducted studies published January 1, 2020, 31, 2025. Included reported on neuroinflammatory biomarkers, events, or dysfunction assessed ≥ 4 weeks after acute SARS-CoV-2 Two independent reviewers screened records, extracted data, appraised study quality using PRISMA 2020 guidelines. narrative synthesis performed, supported by tabulated summaries descriptive visualizations key findings. Results From 2,178 15 (n = 73,435 participants) met inclusion criteria. Three interrelated pathological domains were identified: Neuroimmune Dysregulation: Persistent elevation pro-inflammatory cytokines (e.g., IL-6, TNF-α), microglial activation, neuronal autoantibodies 42% patients, implicating chronic neuroinflammation. Cerebrovascular Complications: 3.7-fold increased stroke risk microvascular injury (22% prevalence) linked SARS-CoV-2-induced endothelial dysfunction, blood-brain barrier disruption, thromboinflammatory pathways. Cognitive Dysfunction: Deficits memory, executive function, processing speed (58% correlated with neuroimaging grey matter atrophy functional connectivity loss. Conclusions Post-acute manifests triad vascular, pathologies, driven synergistic such inflammation. Early detection via multimodal screening neuroimaging, cytokine profiling) multidisciplinary care models are essential mitigate disability. Future research must prioritize standardized diagnostic criteria, elucidating viral neurotropism, trials evaluating therapies targeting stabilization immunomodulation. Addressing priorities will inform evidence-based interventions improve outcomes growing population survivors grappling sequelae.

Язык: Английский

Процитировано

0

Investigating the Neuroimmune, Cerebrovascular, and Cognitive Disturbances Associated with SARS‑CoV‑2 Infection: A Systematic Review of Post‑Acute Outcomes DOI Creative Commons

Hnin Aung

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

Abstract Background SARS-CoV-2, initially identified as a respiratory pathogen, has emerged significant driver of neurological morbidity in the post-acute phase infection. A substantial body evidence underscores persistent neuroimmune dysregulation, cerebrovascular injury, and cognitive impairment critical contributors to long-term disability among COVID-19 survivors. However, mechanistic interplay between these processes their clinical implications remains incompletely characterized. Objectives This systematic review meta-analysis aim (1) elucidate pathophysiological mechanisms underlying outcomes COVID-19, (2) evaluate prevalence spectrum neuroimmune, cerebrovascular, disturbances using both qualitative quantitative data, (3) propose strategies for early detection management based on rigorous, evidence-based findings. Methods comprehensive search PubMed, EMBASE, Cochrane Library was conducted studies published January 1, 2020, 31, 2025. Included reported neuroinflammatory biomarkers, events, or dysfunction assessed ≥ 4 weeks after acute SARS-CoV-2 Two independent reviewers screened records, extracted appraised study quality PRISMA 2020 guidelines. narrative synthesis supplemented by key outcomes, with pooled effect estimates calculated random-effects models address heterogeneity. Results From 2,178 10 (n ≈ 77,300) met inclusion criteria. Three interrelated pathological domains were identified: Neuroimmune Dysregulation: Persistent cytokine elevations (e.g., IL-6, TNF-α), microglial activation, neuronal autoantibodies (detected ~ 18% patients) indicate state chronic neuroinflammation. Cerebrovascular Complications: 3.7-fold increased risk stroke, along blood–brain barrier (BBB) disruption microvascular role endothelial thromboinflammatory pathways. Cognitive Dysfunction: Deficits memory, executive function, processing speed, up 58% patients, correlated neuroimaging findings grey matter atrophy altered functional connectivity. The yielded standardized mean difference IL-6 elevation 0.78 (95% CI: 0.55–1.01; p < 0.001) odds ratio stroke 3.7 2.1–6.4; 0.001). Moderate-to-high heterogeneity (I² 50% 70%) addressed sensitivity analyses, which confirmed robustness associations. Conclusions Post-acute manifests triad vascular, disturbances, supported analyses. Early identification through multimodal screening including advanced neuroimaging, inflammatory biomarker profiling, validated assessments are essential. Targeted therapeutic focusing stabilization immunomodulation may prove pivotal mitigating disability. Future research should prioritize outcome measures further refine interventional approaches inform policy.

Язык: Английский

Процитировано

0

AI-based decoding of long covid cognitive impairments in mice using automated behavioral system and comparative transcriptomic analysis DOI

Heba M. Amer,

Mohamed M. Shamseldin, Sarah Faber

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 15, 2025

Long COVID (LC) following SARS-CoV-2 infection affects millions of individuals world-wide and manifests with a variety symptoms including cognitive dysfunction also known as "brain fog". This is characterized by difficulties in executive functions, planning, decision-making, working memory, impairments complex attention, loss ability to learn new skills perform sophisticated brain tasks. No effective treatment options currently exist for LC-related dysfunction. Here, we use the IntelliCage, which an automated tracking system mice, measuring each mouse within group tasks that mimic human behaviors, such flexibility, memory. Artificial intelligence machine learning analyses data classified LC mice into distinct behavioral categories from non-infected control permitting precise identification quantification controlled, replicable manner. Importantly, find brains exhibit transcriptomic alterations similar those observed humans suffering impairments, altered expression genes involved learning, synaptic neurotransmitters Together, our findings establish validated murine model unbiased approach study first time, providing valuable tool screening potential treatments therapeutic interventions.

Язык: Английский

Процитировано

0

Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments DOI Creative Commons
Rafał Gulej, Roland Patai, Anna Ungvari

и другие.

GeroScience, Год журнала: 2025, Номер unknown

Опубликована: Май 23, 2025

Abstract Aging is a complex biological process that detrimentally affects the brain and cerebrovascular system, contributing to pathogenesis of age-related diseases like vascular cognitive impairment dementia (VCID) Alzheimer’s disease (AD). While cell-autonomous mechanisms occur within cells, independent external signals from neighboring cells or systemic factors, account for some aspects aging, they cannot explain entire aging process. Non-autonomous, paracrine endocrine, pathways also play crucial role in orchestrating aging. The milieu modulates through pro-geronic anti-geronic circulating factors mediate decline confer rejuvenative effects. This review explores impact on with particular focus findings heterochronic parabiosis, blood exchange, plasma transfer experiments. We discuss how these influence fundamental cellular molecular processes endothelial function, neurovascular coupling mechanisms, blood–brain barrier integrity, neuroinflammation, capillary density, amyloid pathologies, significant consequences function. Additionally, we address translational potential challenges modifying promote health prevent impairment.

Язык: Английский

Процитировано

0

The Molecular Mechanisms of Cognitive Dysfunction in Long COVID: A Narrative Review DOI Open Access
Elena Popa, Andrei Emilian Popa,

Mihaela Poroch

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(11), С. 5102 - 5102

Опубликована: Май 26, 2025

Cognitive dysfunction represents one of the most persistent and disabling features Long COVID, yet its molecular underpinnings remain incompletely understood. This narrative review synthesizes current evidence on pathophysiological mechanisms linking SARS-CoV-2 infection to long-term neurocognitive sequelae. Key processes include neuroinflammation, blood–brain barrier (BBB) disruption, endothelial dysfunction, immune dysregulation, neuroendocrine imbalance. Microglial activation cytokine release (e.g., IL-6, TNF-α) promote synaptic neuronal injury, while inflammasomes such as NLRP3 amplifies CNS inflammation. Vascular abnormalities, including microthrombosis BBB leakage, facilitate infiltration peripheral cells neurotoxic mediators. Hypothalamic–pituitary–adrenal axis reduced vagal tone further exacerbate systemic inflammation autonomic Biomarkers GFAP, NFL, S100B have been associated with both neuroinflammation cognitive symptoms. Notably, transcriptomic signatures in COVID overlap those observed Alzheimer’s disease, highlighting shared pathways involving tau oxidative stress, glial reactivity. Understanding these is critical for identifying at-risk individuals developing targeted therapeutic strategies. underscores need longitudinal research integrative biomarker analysis elucidate trajectory impairment COVID.

Язык: Английский

Процитировано

0