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

Innate immune sensors and regulators at the blood brain barrier: focus on toll-like receptors and inflammasomes as mediators of neuro-immune crosstalk and inflammation DOI Creative Commons
Çiğdem Acıoğlu, Stella Elkabes

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Фев. 15, 2025

Cerebral endothelial cells (CEC) that form the brain capillaries are principal constituents of blood barrier (BBB), main active interface between and which plays a protective role by restricting infiltration pathogens, harmful substances immune into while allowing entry essential nutrients. Aberrant CEC function often leads to increased permeability BBB altering bidirectional communication bloodstream facilitating extravasation brain. In addition their as gatekeepers BBB, exhibit cell properties they can receive transmit signals partly via release inflammatory effectors in pathological conditions. express innate receptors, including toll like receptors (TLRs) inflammasomes first sensors exogenous or endogenous dangers initiators responses drive neural dysfunction degeneration. Accumulating evidence indicates activation TLRs compromises integrity, promotes aberrant neuroimmune interactions modulates both systemic neuroinflammation, common features neurodegenerative psychiatric diseases central nervous system (CNS) infections injuries. The goal present review is provide an overview pivotal roles played discuss molecular cellular mechanisms contribute disruption neuroinflammation especially context traumatic ischemic injuries infections. We will focus on most recent advances literature reports field highlight knowledge gaps. future research directions advance our understanding contribution potential at promising therapeutic targets wide variety conditions

Язык: Английский

Процитировано

3
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