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), Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: 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), Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

Citations

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), Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

Citations

0