Postmortem neuropathology in COVID‐19: An update DOI Creative Commons
David S. Younger

Brain Pathology, Journal Year: 2023, Volume and Issue: 33(6)

Published: Aug. 11, 2023

Between 2020 and 2021, Younger [1, 2] described the neuropathology of 144 decedents due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) at height 2019 coronavirus-2 (COVID-19) pandemic. The present study concerns an updated later cohort adding 150 new cases [3-20]. There was a modest demographic shift in cohort. population comprised 12 children 138 adults 2.6:1 ratio males females, age range (7 months 97 years) with 72% ≥50 years, compared earlier whom all were older ages (>age 65 years 79%). Serum cytokine procoagulant levels elevated vast majority patients life both cohorts indicative storm, who managed intensive care unit 86% (equally 88%) until time death that occurred ≤10 days or more (0.78:1). seven COVID-19 associated multisystem inflammatory syndrome (MIS-C) (six patients) including one angiographically negative small vessel childhood primary angiitis central nervous system (AN-SV-cPACNS) [15]. also increase several neuropathological aspects initial early included: Interstitial brainstem inflammation neuronal loss (25% vs. 8%), focal diffuse perivascular parenchymal T-cells (17% 7%), hemorrhagic ischemic infarcts 11% 2% hypoxic–ischemic changes 19%). Positive detection SARS-CoV-2 ribonucleic acid (RNA) by quantitative real-time polymerase chain reaction (qRT-PCR) decreased, while findings increased respectively 44% 9% 22%). Investigations applying commercially available antisense nucleocapsid spike gene probes formalin-fixed paraffin-embedded tissue amplification situ hybridization (ISH) signals employing RNAscope™ [21], counterstained hematoxylin eosin comparison control probes, failed show positivity tissues but did adventitia meningeal outside medulla [20]. Brain microglia activation so noted 21% cases, although rarely mentioned Several salient characterize morbid features neurological illness. Elevated serum cytokines storm likely contribute critical illness, hemorrhagic, thrombotic infarcts. Hypoxic–ischemic seen up quarter may not account for myriad particularly indolent interstitial cerebral mediated predominantly infiltrating CD8 T-cells. Despite overall generally favorable prognosis, systemic CNS contributes mortality pediatric Viral studies typically results RNA isolation qRT-PCR, IHC, ISH. Looking forward, importance performing autopsy resides elucidating potentially humoral adaptive immune responses underlying mechanisms illness COVID-19. Correlative brain imaging utilizing three-dimensional surface projections 18fluorodeoxyglucose positron emission tomography normalized whole fused non-contrast magnetic resonance volumetric analysis previously onset pandemic reveal insights into premorbid affected patients. Severely ill post-acute (PASC) studied prominent cortical hypometabolism widespread areas volume related dysregulated post-infectious response [22]. These neuroimaging clinically correlative notably medial temporal lobe hippocampi attesting duration severity deficits mood neurocognition, appear be influenced microglial transition from surveilling mode reactive state initiating expanding neuroinflammation [23]. author has no conflicts interest report. Data sharing is applicable this article as data created analyzed study.

Language: Английский

Single-cell multiregion dissection of Alzheimer’s disease DOI Creative Commons
Hansruedi Mathys, Carles A. Boix, Leyla Anne Akay

et al.

Nature, Journal Year: 2024, Volume and Issue: 632(8026), P. 858 - 868

Published: July 24, 2024

Abstract Alzheimer’s disease is the leading cause of dementia worldwide, but cellular pathways that underlie its pathological progression across brain regions remain poorly understood 1–3 . Here we report a single-cell transcriptomic atlas six different in aged human brain, covering 1.3 million cells from 283 post-mortem samples 48 individuals with and without disease. We identify 76 cell types, including region-specific subtypes astrocytes excitatory neurons an inhibitory interneuron population unique to thalamus distinct canonical subclasses. vulnerable populations are depleted specific disease, provide evidence Reelin signalling pathway involved modulating vulnerability these neurons. develop scalable method for discovering gene modules, which use cell-type-specific modules altered annotate differences associated diverse variables. astrocyte program cognitive resilience pathology, tying choline metabolism polyamine biosynthesis preserved function late life. Together, our study develops regional ageing provides insights into vulnerability, response pathology.

Language: Английский

Citations

62
Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms DOI Open Access
Ann‐Charlotte Granholm

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(9), P. 3190 - 3190

Published: April 28, 2023

Numerous investigations have demonstrated significant and long-lasting neurological manifestations of COVID-19. It has been suggested that as many four out five patients who sustained COVID-19 will show one or several symptoms can last months after the infection run its course. Neurological are most common in people less than 60 years age, while encephalopathy is more those over 60. Biological mechanisms for these need to be investigated may include both direct indirect effects virus on brain spinal cord. Individuals with Alzheimer’s disease (AD) related dementia, well persons Down syndrome (DS), especially vulnerable COVID-19, but biological reasons this not clear. Investigating consequences an urgent emerging medical need, since close 700 million worldwide now had at least once. likely there a new burden healthcare economy dealing long-term severe SARS-CoV-2 infections long COVID, even younger generations. Interestingly, acute strikingly similar observed mild traumatic injury (mTBI) concussion, including dizziness, balance issues, anosmia, headaches. The possible convergence pathways involved discussed. current review focused commonly described symptoms, molecular involved.

Language: Английский

Citations

24
Engineered Wnt7a ligands rescue blood–brain barrier and cognitive deficits in a COVID-19 mouse model DOI Creative Commons
Troy N. Trevino, A Fogel,

Guliz Otkiran

et al.

Brain, Journal Year: 2024, Volume and Issue: 147(5), P. 1636 - 1643

Published: Feb. 2, 2024

Abstract Respiratory infection with SARS-CoV-2 causes systemic vascular inflammation and cognitive impairment. We sought to identify the underlying mechanisms mediating cerebrovascular dysfunction following mild respiratory infection. To this end, we performed unbiased transcriptional analysis brain endothelial cell signalling pathways dysregulated by mouse adapted MA10 in aged immunocompetent C57Bl/6 mice vivo. This revealed significant suppression of Wnt/β-catenin signalling, a critical regulator blood–brain barrier (BBB) integrity. therefore hypothesized that enhancing activity would offer protection against BBB permeability, neuroinflammation, neurological signs acute Indeed, found delivery cerebrovascular-targeted, engineered Wnt7a ligands protected integrity, reduced T-cell infiltration brain, microglial activation Importantly, strategy also mitigated induced deficits novel object recognition assay for learning memory pole descent task bradykinesia. These observations suggest enhancement or its downstream effectors could be potential interventional strategies restoring health viral infections.

Language: Английский

Citations

11
Caveolin-1 mediates blood-brain barrier permeability, neuroinflammation, and cognitive impairment in SARS-CoV-2 infection DOI Creative Commons
Troy N. Trevino, Ali A. Almousawi, KaReisha F. Robinson

et al.

Journal of Neuroimmunology, Journal Year: 2024, Volume and Issue: 388, P. 578309 - 578309

Published: Feb. 4, 2024

Blood-brain barrier (BBB) permeability can cause neuroinflammation and cognitive impairment. Caveolin-1 (Cav-1) critically regulates BBB permeability, but its influence on the consequent neurological outcomes in respiratory viral infections is unknown. We used Cav-1-deficient mice with genetically encoded fluorescent endothelial tight junctions to determine how Cav-1 influences neuroinflammation, impairment following infection mouse adapted (MA10) SARS-CoV-2 as a model for COVID-19. found that increased brain transcellular albumin, decreased paracellular Claudin-5 junctions, caused T lymphocyte infiltration hippocampus, region important learning memory. Concordantly, we observed memory deficits infected mice. Importantly, genetic deficiency attenuated junction losses, infiltration, gliosis induced by infection. Moreover, KO were protected from These results establish contribution of behavioral dysfunction neuroinflammation.

Language: Английский

Citations

9
SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature DOI Creative Commons
Laetitia Lebrun, Lara Absil, Myriam Remmelink

et al.

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: May 10, 2023

Abstract Introduction COVID-19-infected patients harbour neurological symptoms such as stroke and anosmia, leading to the hypothesis that there is direct invasion of central nervous system (CNS) by SARS-CoV-2. Several studies have reported neuropathological examination brain samples from who died COVID-19. However, still sparse evidence virus replication in human brain, suggesting neurologic could be related mechanisms other than CNS infection virus. Our objective was provide an extensive review literature on findings postmortem COVID-19 report our own experience with 18 samples. Material methods We used microscopic examination, immunohistochemistry (using two different antibodies) PCR-based techniques describe presence SARS-CoV-2 For comparison, similar (IHC PCR) were applied lung tissue for each patient cohort. The systematic conducted beginning pandemic 2019 until June 1st, 2022. Results In cohort, most common perivascular haemosiderin-laden macrophages hypoxic-ischaemic changes neurons, which found all cases (n = 18). Only one sample harboured viral spike nucleocapsid protein expression, while RNA positivity PCR. A colocalization study revealed antigens located macrophages. highlighted frequent ischaemic haemorrhagic lesions, including hypoxic/ischaemic alterations. few confirmed Conclusion This lack specific alterations patients. There no neurotropism cohort or literature.

Language: Английский

Citations

19
On the merits and potential of advanced neuroimaging techniques in COVID-19: A scoping review DOI Creative Commons
Noa van der Knaap, Marcel Aries, Iwan C.C. van der Horst

et al.

NeuroImage Clinical, Journal Year: 2024, Volume and Issue: 42, P. 103589 - 103589

Published: Jan. 1, 2024

Many Coronavirus Disease 2019 (COVID-19) patients are suffering from long-term neuropsychological sequelae. These may benefit a better understanding of the underlying neuropathophysiological mechanisms and identification potential biomarkers treatment targets. Structural clinical neuroimaging techniques have limited ability to visualize subtle cerebral abnormalities investigate brain function. This scoping review assesses merits advanced in COVID-19 using literature including or postmortem analyses adult published start pandemic until December 2023. Findings were summarized according distinct categories reported revealed by different imaging techniques. Although no unified COVID-19-specific pattern could be subtracted, broad range (likely attributable hypoxic, vascular, inflammatory pathology), even absence structural findings. validated examinations. emphasizes added value compared highlights implications for functioning consequences COVID-19.

Language: Английский

Citations

4
Brain Findings in Deceased COVID-19 Patients DOI
Armaan Shergill,

Bennet Omalu,

Peter Conner

et al.

American Journal of Forensic Medicine & Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Abstract As COVID-19 continues to infect millions of people globally, it is essential understand how SARS-CoV-2 affects the brain. The purpose this study determine if there are any associations or patterns gross and microscopic neuropathological autopsy findings in brains patients who died from COVID-19. We analyzed 32 cases that met 3 requirements: (1) positive polymerase chain reaction (PCR) test at autopsy; (2) pulmonary histological features SARS-CoV-2; (3) complete autopsies conducted during pandemic 2020 2023. accounted for presence following findings: cerebral edema (CE), cortical atrophy (CCA), chronic cerebrovascular disease (CCD), ischemic injury (CII), inflammation (CIN), and/or parenchymal hemorrhage (CPH) every case. found CE, CCA, CII diagnoses had a statistically significant association with age. There were no distinctive recurrent alterations autopsied may be interpreted pathognomonic infection our cohort. These suggest not associated distinct histomorphologic abnormalities diagnostic patients.

Language: Английский

Citations

0
Elevated neuroinflammation, autoimmunity, and altered IgG glycosylation profile in the cerebral spinal fluid of severe COVID-19 patients DOI

Tanner Shull,

Pavan Bhimalli,

Samantha J. Welninski

et al.

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
A year in review: brain barriers and brain fluids research in 2022 DOI Creative Commons
Richard F. Keep,

Hazel C. Jones,

Mark G. Hamilton

et al.

Fluids and Barriers of the CNS, Journal Year: 2023, Volume and Issue: 20(1)

Published: April 21, 2023

This aim of this editorial is to highlight progress made in brain barrier and fluid research 2022. It covers studies on the blood-brain, blood-retina blood-CSF barriers (choroid plexus meninges), signaling within neurovascular unit elements systems. further discusses how systems are impacted CNS diseases, their role disease progression being treating such diseases.

Language: Английский

Citations

8
Neuroimaging findings of COVID-19: a systematic review on longitudinal studies DOI Creative Commons
Fardin Nabizadeh, Mohammad Sadegh Fallahi,

Rasa Zafari

et al.

Neurology Letters, Journal Year: 2024, Volume and Issue: 3(1), P. 27 - 36

Published: Jan. 1, 2024

Background: There is high number of evidence regarding the involvement central nervous system (CNS) in patients with severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). The aim our systematic review study to evaluate current state knowledge neuroimaging findings after COVID-19 by focusing on longitudinal studies. By limiting this type design, we aimed provide a more comprehensive and detailed picture long-term effects brain.Methods: Three electronic databases (PubMed, Scopus, Web Science) were searched for relevant We included studies that investigated brain changes available at least two different times.Results: After two-step review, 10 qualitative synthesis. Brain MRI was only imaging modality seven studies, whereas one used FDG-PET, CT/MRI, CT/MRI/FDG-PET. Our results demonstrated consistent lesions, white matter microstructural, grey matter, metabolism, blood flow alterations comparison healthy controls.Conclusion: provides widespread afflicted COVID-19. nature highlights importance ongoing monitoring follow-up infection.

Language: Английский

Citations

2