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1.
Brain Behav Immun ; 87: 18-22, 2020 07.
Article in English | MEDLINE | ID: covidwho-1719333

ABSTRACT

Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.


Subject(s)
Coronavirus Infections/physiopathology , Nervous System Diseases/physiopathology , Pneumonia, Viral/physiopathology , Betacoronavirus , COVID-19 , Consciousness Disorders/etiology , Consciousness Disorders/physiopathology , Coronavirus 229E, Human , Coronavirus Infections/complications , Coronavirus NL63, Human , Coronavirus OC43, Human , Dysgeusia/etiology , Dysgeusia/physiopathology , Encephalitis/etiology , Encephalitis/physiopathology , Encephalitis, Viral/etiology , Encephalitis, Viral/physiopathology , Guillain-Barre Syndrome/etiology , Guillain-Barre Syndrome/physiopathology , Humans , Middle East Respiratory Syndrome Coronavirus , Nervous System Diseases/etiology , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/physiopathology , Neurotoxicity Syndromes/virology , Olfaction Disorders/etiology , Olfaction Disorders/physiopathology , Pandemics , Pneumonia, Viral/complications , Polyneuropathies/etiology , Polyneuropathies/physiopathology , SARS Virus , SARS-CoV-2 , Seizures/etiology , Seizures/physiopathology , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/physiopathology , Stroke/etiology , Stroke/physiopathology
2.
Neurophotonics ; 8(2): 025002, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1666346

ABSTRACT

Significance: High-density diffuse optical tomography (HD-DOT) has been shown to approach the resolution and localization accuracy of blood oxygen level dependent-functional magnetic resonance imaging in the adult brain by exploiting densely spaced, overlapping samples of the probed tissue volume, but the technique has to date required large and cumbersome optical fiber arrays. Aim: To evaluate a wearable HD-DOT system that provides a comparable sampling density to large, fiber-based HD-DOT systems, but with vastly improved ergonomics. Approach: We investigated the performance of this system by replicating a series of classic visual stimulation paradigms, carried out in one highly sampled participant during 15 sessions to assess imaging performance and repeatability. Results: Hemodynamic response functions and cortical activation maps replicate the results obtained with larger fiber-based systems. Our results demonstrate focal activations in both oxyhemoglobin and deoxyhemoglobin with a high degree of repeatability observed across all sessions. A comparison with a simulated low-density array explicitly demonstrates the improvements in spatial localization, resolution, repeatability, and image contrast that can be obtained with this high-density technology. Conclusions: The system offers the possibility for minimally constrained, spatially resolved functional imaging of the human brain in almost any environment and holds particular promise in enabling neuroscience applications outside of the laboratory setting. It also opens up new opportunities to investigate populations unsuited to traditional imaging technologies.

3.
Eur J Neurol ; 28(10): 3491-3502, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1607956

ABSTRACT

BACKGROUND AND PURPOSE: Although COVID-19 predominantly affects the respiratory system, recent studies have reported the occurrence of neurological disorders such as stroke in relation to COVID-19 infection. Encephalitis is an inflammatory condition of the brain that has been described as a severe neurological complication of COVID-19. Despite a growing number of reported cases, encephalitis related to COVID-19 infection has not been adequately characterised. To address this gap, this systematic review and meta-analysis aims to describe the incidence, clinical course, and outcomes of patients who suffer from encephalitis as a complication of COVID-19. METHODS: All studies published between 1 November 2019 and 24 October 2020 that reported on patients who developed encephalitis as a complication of COVID-19 were included. Only cases with radiological and/or biochemical evidence of encephalitis were included. RESULTS: In this study, 610 studies were screened and 23 studies reporting findings from 129,008 patients, including 138 with encephalitis, were included. The average time from diagnosis of COVID-19 to onset of encephalitis was 14.5 days (range = 10.8-18.2 days). The average incidence of encephalitis as a complication of COVID-19 was 0.215% (95% confidence interval [CI] = 0.056%-0.441%). The average mortality rate of encephalitis in COVID-19 patients was 13.4% (95% CI = 3.8%-25.9%). These patients also had deranged clinical parameters, including raised serum inflammatory markers and cerebrospinal fluid pleocytosis. CONCLUSIONS: Although encephalitis is an uncommon complication of COVID-19, when present, it results in significant morbidity and mortality. Severely ill COVID-19 patients are at higher risk of suffering from encephalitis as a complication of the infection.


Subject(s)
COVID-19 , Encephalitis , Nervous System Diseases , Encephalitis/epidemiology , Encephalitis/etiology , Humans , Incidence , SARS-CoV-2
4.
Eur J Neurol ; 28(10): 3443-3447, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1607745

ABSTRACT

BACKGROUND AND PURPOSE: COVID-19 affects the brain in various ways, amongst which delirium is worrying. An assessment was made of whether a specific, long-lasting, COVID-19-related brain injury develops in acute respiratory distress syndrome patients after life-saving re-oxygenation. METHODS: Ten COVID+ patients (COVID+) with unusual delirium associated with neuroimaging suggestive of diffuse brain injury and seven controls with non-COVID encephalopathy were studied. The assessment took place when the intractable delirium started at weaning off ventilation support. Brain magnetic resonance imaging (MRI) was performed followed by standard cerebrospinal fluid (CSF) analyses and assessment of CSF erythropoietin concentrations (as a marker for the assessment of tissue repair), and of non-targeted CSF metabolomics using liquid chromatography high resolution mass spectrometry. RESULTS: Patients were similar as regards severity scores, but COVID+ were hospitalized longer (25 [11.75; 25] vs. 9 [4.5; 12.5] days, p = 0.03). On admission, but not at MRI and lumbar puncture performance, COVID+ were more hypoxic (p = 0.002). On MRI, there were leptomeningeal enhancement and diffuse white matter haemorrhages only in COVID+. In the latter, CSF erythropoietin concentration was lower (1.73 [1.6; 2.06] vs. 3.04 [2.9; 3.91] mIU/ml, p = 0.01), and CSF metabolomics indicated (a) increased compounds such as foodborne molecules (sesquiterpenes), molecules from industrialized beverages and micro-pollutants (diethanolamine); and (b) decreased molecules such as incomplete breakdown products of protein catabolism and foodborne molecules (glabridin). At 3-month discharge, fatigue, anxiety and depression as well as MRI lesions persisted in COVID+. CONCLUSIONS: Some COVID+ are at risk of a specific delirium. Imperfect brain repair after re-oxygenation and lifestyle factors might influence long-lasting brain injuries in a context of foodborne micro-pollutants.


Subject(s)
COVID-19 , Delirium , Environmental Pollutants , Brain/diagnostic imaging , Critical Care , Humans , SARS-CoV-2
5.
eNeuro ; 8(3)2021.
Article in English | MEDLINE | ID: covidwho-1551335

ABSTRACT

The Coronavirus disease-2019 (COVID-19) presents a variability of clinical symptoms, ranging from asymptomatic to severe respiratory and systemic conditions. In a cohort of patients, the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), beyond the classical respiratory manifestations, induces anosmia. Evidence has suggested SARS-CoV-2-induced anosmia can be the result of neurodegeneration of the olfactory pathway. Neurologic symptoms associated with COVID-19 have been reported; however, the precise mechanism and possible long-lasting effects remain poorly investigated. Preclinical models are valuable tools for describing and testing new possible treatments for neurologic disorders. In this way, the zebrafish (Danio rerio) organism model represents an attractive tool in the field of neuroscience, showing economic and logistic advantages besides genetic and physiologic similarities with mammalian, including the brain structure and functions. Besides, its external embryonic development, high availability of eggs, and fast development allows easy genetic manipulation and fast replications. In the present review, we suggest that the zebrafish model can be advantageous to investigate the neurologic features of COVID-19.


Subject(s)
COVID-19 , Nervous System Diseases , Animals , Anosmia , Humans , SARS-CoV-2 , Zebrafish
6.
Lancet Respir Med ; 9(5): 533-544, 2021 05.
Article in English | MEDLINE | ID: covidwho-1537202

ABSTRACT

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Cough/etiology , Inflammation/etiology , Nervous System Diseases/etiology , Neuroimmunomodulation , Cough/physiopathology , Humans , Inflammation/physiopathology , Nervous System Diseases/physiopathology , SARS-CoV-2 , Syndrome
7.
Eur J Neurol ; 28(8): 2603-2613, 2021 08.
Article in English | MEDLINE | ID: covidwho-1518029

ABSTRACT

BACKGROUND AND PURPOSE: Nasu-Hakola disease (NHD) is a rare, autosomal recessive disorder characterized by skeletal and neurological symptoms. Behavioral symptoms with cognitive impairment may mimic the behavioral variant of frontotemporal dementia (bvFTD) and other early-onset dementias. Our patients were analyzed and the literature was reviewed to delineate neurological and neuroimaging findings suggestive of NHD. METHOD: Fourteen patients carrying a pathogenic mutation in the TREM2 gene were found in our database. Demographic, clinical, laboratory and radiological data were retrieved and analyzed. RESULTS: The presenting clinical picture was behavioral changes with cognitive decline resembling bvFTD in all patients. The mean age was 37.1 ± 4.97 years and the mean duration of the disease was 8.9 ± 3.51 years. Only two patients had typical bone cysts. Seven patients had bilateral calcification of the basal ganglia in computed tomography of the brain. Magnetic resonance imaging of the brain revealed severe atrophy of the corpus callosum, enlargement of the ventricles, atrophy of the caudate nuclei and periventricular white matter changes in all patients. Symmetrical global atrophy of the brain mainly affecting frontoparietal and lateral temporal regions were observed in all cases, and 13 patients had atrophy of the hippocampus. Cerebrospinal fluid examination of 10 patients showed elevated protein levels in six and the presence of oligoclonal bands in four patients. CONCLUSION: A combination of white matter changes, enlarged ventricles, atrophy of the caudate nuclei and thinning of the corpus callosum in magnetic resonance imaging strongly suggests NHD in patients with FTD syndrome. Molecular genetic analysis should be performed in suspected cases, and families should receive genetic counseling.


Subject(s)
Frontotemporal Dementia , Lipodystrophy , Membrane Glycoproteins/genetics , Osteochondrodysplasias , Receptors, Immunologic/genetics , Subacute Sclerosing Panencephalitis , Adult , Brain/diagnostic imaging , Frontotemporal Dementia/diagnostic imaging , Frontotemporal Dementia/genetics , Humans , Magnetic Resonance Imaging , Neuroimaging
8.
Neurocrit Care ; 35(2): 577-589, 2021 10.
Article in English | MEDLINE | ID: covidwho-1516917

ABSTRACT

BACKGROUND: Multiple studies demonstrate that fever/elevated temperature is associated with poor outcomes in patients with vascular brain injury; however, there are no conclusive studies that demonstrate that fever prevention/controlled normothermia is associated with better outcomes. The primary objective of the INTREPID (Impact of Fever Prevention in Brain-Injured Patients) trial is to test the hypothesis that fever prevention is superior to standard temperature management in patients with acute vascular brain injury. METHODS: INTREPID is a prospective randomized open blinded endpoint study of fever prevention versus usual care in patients with ischemic or hemorrhagic stroke. The fever prevention intervention utilizes the Arctic Sun System and will be compared to standard care patients in whom fever may spontaneously develop. Ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage patients will be included within disease-specific time-windows. Both awake and sedated patients will be included, and treatment is initiated immediately upon enrollment. Eligible patients are expected to require intensive care for at least 72 h post-injury, will not be deemed unlikely to survive without severe disability, and will be treated for up to 14 days, or until deemed ready for discharge from the ICU, whichever comes first. Fifty sites in the USA and worldwide will participate, with a target enrollment of 1176 patients (1000 evaluable). The target temperature is 37.0 °C. The primary efficacy outcome is the total fever burden by °C-h, defined as the area under the temperature curve above 37.9 °C. The primary secondary outcome, on which the sample size is based, is the modified Rankin Scale Score at 3 months. All efficacy analyses including the primary and key secondary endpoints will be primarily based on an intention-to-treat population. Analysis of the as-treated and per protocol populations will also be performed on the primary and key secondary endpoints as sensitivity analyses. DISCUSSION: The INTREPID trial will provide the first results of the impact of a pivotal fever prevention intervention in patients with acute stroke ( www.clinicaltrials.gov ; NCT02996266; registered prospectively 05DEC2016).


Subject(s)
COVID-19 , Brain , Critical Care , Humans , Prospective Studies , Randomized Controlled Trials as Topic , SARS-CoV-2
9.
Dev Neurosci ; 43(3-4): 143-158, 2021.
Article in English | MEDLINE | ID: covidwho-1472320

ABSTRACT

The mechanistic target of rapamycin (mTOR) is a kinase at the center of an evolutionarily conserved signaling pathway that orchestrates cell growth and metabolism. mTOR responds to an array of intra- and extracellular stimuli and in turn controls multiple cellular anabolic and catabolic processes. Aberrant mTOR activity is associated with numerous diseases, with particularly profound impact on the nervous system. mTOR is found in two protein complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which are governed by different upstream regulators and have distinct cellular actions. Mutations in genes encoding for mTOR regulators result in a collection of neurodevelopmental disorders known as mTORopathies. While these disorders can affect multiple organs, neuropsychiatric conditions such as epilepsy, intellectual disability, and autism spectrum disorder have a major impact on quality of life. The neuropsychiatric aspects of mTORopathies have been particularly challenging to treat in a clinical setting. Current therapeutic approaches center on rapamycin and its analogs, drugs that are administered systemically to inhibit mTOR activity. While these drugs show some clinical efficacy, adverse side effects, incomplete suppression of mTOR targets, and lack of specificity for mTORC1 or mTORC2 may limit their utility. An increased understanding of the neurobiology of mTOR and the underlying molecular, cellular, and circuit mechanisms of mTOR-related disorders will facilitate the development of improved therapeutics. Animal models of mTORopathies have helped unravel the consequences of mTOR pathway mutations in specific brain cell types and developmental stages, revealing an array of disease-related phenotypes. In this review, we discuss current progress and potential future directions for the therapeutic treatment of mTORopathies with a focus on findings from genetic mouse models.


Subject(s)
Autism Spectrum Disorder , Animals , Humans , Mechanistic Target of Rapamycin Complex 1/metabolism , Mechanistic Target of Rapamycin Complex 2/metabolism , Mice , Quality of Life , Signal Transduction
10.
Eur J Nucl Med Mol Imaging ; 48(10): 3187-3197, 2021 09.
Article in English | MEDLINE | ID: covidwho-1396993

ABSTRACT

PURPOSE: The present study hypothesised that whole-body [18F]FDG-PET/CT might provide insight into the pathophysiology of long COVID. METHODS: We prospectively enrolled 13 adult long COVID patients who complained for at least one persistent symptom for >30 days after infection recovery. A group of 26 melanoma patients with negative PET/CT matched for sex/age was used as controls (2:1 control to case ratio). Qualitative and semi-quantitative analysis of whole-body images was performed. Fisher exact and Mann-Whitney tests were applied to test differences between the two groups. Voxel-based analysis was performed to compare brain metabolism in cases and controls. Cases were further grouped according to prevalent symptoms and analysed accordingly. RESULTS: In 4/13 long COVID patients, CT images showed lung abnormalities presenting mild [18F]FDG uptake. Many healthy organs/parenchyma SUVs and SUV ratios significantly differed between the two groups (p ≤ 0.05). Long COVID patients exhibited brain hypometabolism in the right parahippocampal gyrus and thalamus (uncorrected p < 0.001 at voxel level). Specific area(s) of hypometabolism characterised patients with persistent anosmia/ageusia, fatigue, and vascular uptake (uncorrected p < 0.005 at voxel level). CONCLUSION: [18F]FDG PET/CT acknowledged the multi-organ nature of long COVID, supporting the hypothesis of underlying systemic inflammation. Whole-body images showed increased [18F]FDG uptake in several "target" and "non-target" tissues. We found a typical pattern of brain hypometabolism associated with persistent complaints at the PET time, suggesting a different temporal sequence for brain and whole-body inflammatory changes. This evidence underlined the potential value of whole-body [18F]FDG PET in disclosing the pathophysiology of long COVID.


Subject(s)
COVID-19 , Fluorodeoxyglucose F18 , Adult , COVID-19/complications , Case-Control Studies , Humans , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , SARS-CoV-2
11.
CNS Neurosci Ther ; 27(1): 36-47, 2021 01.
Article in English | MEDLINE | ID: covidwho-1388231

ABSTRACT

The blood-brain barrier (BBB) is an important physiological barrier that separates the central nervous system (CNS) from the peripheral circulation, which contains inflammatory mediators and immune cells. The BBB regulates cellular and molecular exchange between the blood vessels and brain parenchyma. Normal functioning of the BBB is crucial for the homeostasis and proper function of the brain. It has been demonstrated that peripheral inflammation can disrupt the BBB by various pathways, resulting in different CNS diseases. Recently, clinical research also showed CNS complications following SARS-CoV-2 infection and chimeric antigen receptor (CAR)-T cell therapy, which both lead to a cytokine storm in the circulation. Therefore, elucidation of the mechanisms underlying the BBB disruption induced by peripheral inflammation will provide an important basis for protecting the CNS in the context of exacerbated peripheral inflammatory diseases. In the present review, we first summarize the physiological properties of the BBB that makes the CNS an immune-privileged organ. We then discuss the relevance of peripheral inflammation-induced BBB disruption to various CNS diseases. Finally, we elaborate various factors and mechanisms of peripheral inflammation that disrupt the BBB.


Subject(s)
Blood-Brain Barrier/metabolism , Brain/metabolism , COVID-19/metabolism , Inflammation Mediators/metabolism , Animals , Blood-Brain Barrier/immunology , Blood-Brain Barrier/pathology , Brain/immunology , Brain/pathology , COVID-19/immunology , COVID-19/pathology , Endothelial Cells/immunology , Endothelial Cells/metabolism , Humans , Inflammation/immunology , Inflammation/metabolism , Inflammation/pathology , Inflammation Mediators/immunology
13.
Philosophia (Ramat Gan) ; 50(1): 321-335, 2022.
Article in English | MEDLINE | ID: covidwho-1384558

ABSTRACT

One of the criteria to a strong principle in natural sciences is simplicity. The conventional view holds that the world is provided with natural laws that must be simple. This common-sense approach is a modern rewording of the medieval philosophical/theological concept of the Multiple arising from (and generated by) the One. Humans need to pursue unifying frameworks, classificatory criteria and theories of everything. Still, the fact that our cognitive abilities tend towards simplification and groupings does not necessarily entail that this is the way the world works. Here we ask: what if singularity does not pave the way to multiplicity? How will we be sure if the Ockham's razor holds in real life? We will show in the sequel that the propensity to reduce to simplicity the relationships among the events leads to misleading interpretations of scientific issues. We are not going to take a full sceptic turn: we will engage in active outreach, suggesting examples from biology and physics to demonstrate how a novel methodological antiunitary approach might help to improve our scientific attitude towards world affairs. We will provide examples from aggregation of SARS-Cov-2 particles, unclassified extinct creatures, pathological brain stiffness. Further, we will describe how antiunitary strategies, plagiarising medieval concepts from William od Ockham and Gregory of Rimini, help to explain novel relational approaches to quantum mechanics and the epistemological role of our mind in building the real world.

14.
Cureus ; 12(11): e11452, 2020 Nov 12.
Article in English | MEDLINE | ID: covidwho-1389783

ABSTRACT

Previous reports have shown various neurological manifestations in about 36.4% of patients infected with SARS-Cov-2. However, peripheral neuropathy was only reported once before. A 40-year-old healthy woman presented with two weeks of cough, nasal congestion, sore throat, intermittent fevers, fatigue, and myalgia but no weakness. She tested positive for the SARS-Cov-2. Physical exam showed no neurologic deficit. Two weeks later, respiratory symptoms were improving but she developed sudden leg pain, numbness, and weakness. She described it as a "pain crisis". Neurological exam showed bilateral symmetrical, non-ascending lower extremity weakness and normal, symmetric reflexes. She had normal magnetic resonance imaging of the brain and spine, spinal fluid analysis, serum studies including creatinine kinase and C-reactive protein. She had elevated lactate dehydrogenase, low serum copper (72.9 (ref: 80.0-155.0 ug/dL)) and low vitamin B6 (14.6 (ref: 20.0-125.0 nmol/L)). A diagnosis of SARS-Cov-2-associated peripheral neuropathy was considered. We pursued empiric treatment with intravenous steroids (1000 mg methylprednisolone for three days), followed by a total of 2 g/kg of intravenous immunoglobulins (IVIG) given over five days. Pain management was done with gabapentin and ketorolac. We replaced copper and vitamin B6. Six weeks later, she reported improvement and was closer to baseline, but she endorsed residual, exertional, mild bilateral lower extremity pain, numbness, and weakness. Previous reports of treatment of SARS-Cov-2-associated neuropathy included corticosteroids and IVIG. Our patient saw the most symptomatic improvement with gabapentin. In our case, the preserved reflexes, lack of ascending pattern, sudden onset of symptoms, and normal cerebrospinal fluid (CSF) argued against Guillain-Barre syndrome. Copper deficiency can result in myelopathy but not peripheral neuropathy, so is unlikely the sole explanation. Awareness and early treatment of peripheral neuropathy in SARS-Cov-2 can result in improved clinical outcomes for patients.

15.
Front Immunol ; 11: 565521, 2020.
Article in English | MEDLINE | ID: covidwho-1389164

ABSTRACT

Neurological disorders caused by neuroviral infections are an obvious pathogenic manifestation. However, non-neurotropic viruses or peripheral viral infections pose a considerable challenge as their neuropathological manifestations do not emerge because of primary infection. Their secondary or bystander pathologies develop much later, like a syndrome, during and after the recovery of patients from the primary disease. Massive inflammation caused by peripheral viral infections can trigger multiple neurological anomalies. These neurological damages may range from a general cognitive and motor dysfunction up to a wide spectrum of CNS anomalies, such as Acute Necrotizing Hemorrhagic Encephalopathy, Guillain-Barré syndrome, Encephalitis, Meningitis, anxiety, and other audio-visual disabilities. Peripheral viruses like Measles virus, Enteroviruses, Influenza viruses (HIN1 series), SARS-CoV-1, MERS-CoV, and, recently, SARS-CoV-2 are reported to cause various neurological manifestations in patients and are proven to be neuropathogenic even in cellular and animal model systems. This review presents a comprehensive picture of CNS susceptibilities toward these peripheral viral infections and explains some common underlying themes of their neuropathology in the human brain.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/complications , Coronavirus Infections/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , Neurogenic Inflammation/complications , Neurogenic Inflammation/immunology , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , SARS Virus/immunology , Severe Acute Respiratory Syndrome/complications , Animals , Blood-Brain Barrier/immunology , Blood-Brain Barrier/virology , COVID-19 , Coronavirus Infections/virology , Cytokines/blood , Disease Models, Animal , Humans , Microglia/immunology , Microglia/virology , Neurogenic Inflammation/virology , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/virology
16.
iScience ; 23(12): 101806, 2020 Dec 18.
Article in English | MEDLINE | ID: covidwho-1385755

ABSTRACT

By testing pseudotyped SARS-CoV-2 and HIV-based lentivirus, this study reports that exosomes/microvesicles (Ex/Mv) isolated from murine hypothalamic neural stem/progenitor cells (htNSC) or subtype htNSCPGHM as well as hippocampal NSC have innate immunity-like actions against these RNA viruses. These extracellular vesicles also have a cell-free innate antiviral action by attacking and degrading viruses. We further generated the induced versions of Ex/Mv through prior viral exposure to NSCs and found that these induced Ex/Mv were stronger than basal Ex/Mv in reducing the infection of these viruses, suggesting the involvement of an adaptive immunity-like antiviral function. These NSC Ex/Mv were found to be characterized by producing large libraries of P element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) against genomes of various viruses, and some of these piRNAs were enriched during the adaptive immunity-like reaction, possibly contributing to the antiviral effects of these Ex/Mv. In conclusion, NSC Ex/Mv have antiviral immunity and could potentially be developed to combat against various viruses.

17.
J Neuroophthalmol ; 41(3): 285-292, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1367097

ABSTRACT

BACKGROUND: Patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may present or eventually develop central nervous system and ophthalmic signs and symptoms. Varying reports have emerged regarding isolation of viral RNA from these tissue sites, as well as largely autopsy-based histopathologic descriptions of the brain and the eye in patients with COVID-19. EVIDENCE ACQUISITION: A primary literature search was performed in literature databases such as PubMed, Google Scholar, and Cochrane Library. Keywords were used alone and in combination including the following: SARS CoV-2, COVID-19, eye, brain, central nervous system, histopathology, autopsy, ocular pathology, aqueous, tears, vitreous, neuropathology, and encephalitis. RESULTS: The reported ophthalmic pathologic and neuropathologic findings in patients with SARS-CoV-2 are varied and inconclusive regarding the role of direct viral infection vs secondary pathology. The authors own experience with autopsy neuropathology in COVID-19 patients is also described. There is a particular paucity of data regarding the histopathology of the eye. However, it is likely that the ocular surface is a potential site for inoculation and the tears a source of spread of viral particles. CONCLUSIONS: Additional large postmortem studies are needed to clarify the role of SARS-CoV in the ophthalmic and neuropathologic manifestations of COVID-19.


Subject(s)
Brain/diagnostic imaging , COVID-19/complications , Eye Diseases/diagnosis , Eye/diagnostic imaging , Nervous System Diseases/diagnosis , COVID-19/epidemiology , Eye Diseases/etiology , Humans , Nervous System Diseases/etiology , Pandemics
18.
Chin Med J (Engl) ; 134(2): 143-150, 2021 01 05.
Article in English | MEDLINE | ID: covidwho-1307571

ABSTRACT

ABSTRACT: Age-related sporadic cerebral small vessel disease (CSVD) has gained increasing attention over the past decades because of its increasing prevalence associated with an aging population. The widespread application of and advances in brain magnetic resonance imaging in recent decades have significantly increased researchers' understanding in the in vivo evolution of CSVD, its impact upon the brain, its risk factors, and the mechanisms that explain the various clinical manifestation associated with sporadic CSVD. In this review, we aimed to provide an update on the pathophysiology, risk factors, biomarkers, and the determinants and spectrum of the clinical manifestation of sporadic CSVD.


Subject(s)
Cerebral Small Vessel Diseases , Pandemics , Aged , Aging , Brain/diagnostic imaging , Cerebral Small Vessel Diseases/diagnostic imaging , Cerebral Small Vessel Diseases/epidemiology , Humans , Magnetic Resonance Imaging
19.
J Neurosurg ; : 1-4, 2020 Sep 04.
Article in English | MEDLINE | ID: covidwho-1304575

ABSTRACT

Herein, the authors present the case of a 54-year-old male diagnosed with coronavirus disease 2019 (COVID-19) during a screening test. The patient was asked to self-isolate at home and report with any exacerbations of symptoms. He presented later with pneumonia complicated by encephalopathy at days 14 and 15 from initial diagnosis, respectively. MRI of the brain showed bithalamic and gangliocapsular FLAIR signal abnormality with mild right-sided thalamic and periventricular diffusion restriction. A CT venogram was obtained given the distribution of edema and demonstrated deep venous thrombosis involving the bilateral internal cerebral veins and the vein of Galen. CSF workup was negative for encephalitis, as the COVID-19 polymerase chain reaction (PCR) test and bacterial cultures were negative. A complete hypercoagulable workup was negative, and the venous thrombosis was attributed to a hypercoagulable state induced by COVID-19. The mental decline was attributed to bithalamic and gangliocapsular venous infarction secondary to deep venous thrombosis. Unfortunately, the patient's condition continued to decline, and care was withdrawn.

20.
Eur J Nucl Med Mol Imaging ; 48(9): 2823-2833, 2021 08.
Article in English | MEDLINE | ID: covidwho-1298551

ABSTRACT

PURPOSE: In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent recovery from COVID-19. This clinical presentation has been referred as "long COVID." We here present a retrospective analysis of 18F-FDG brain PET of long COVID patients from the same center with a biologically confirmed diagnosis of SARS-CoV-2 infection and persistent functional complaints at least 3 weeks after the initial infection. METHODS: PET scans of 35 patients with long COVID were compared using whole-brain voxel-based analysis to a local database of 44 healthy subjects controlled for age and sex to characterize cerebral hypometabolism. The individual relevance of this metabolic profile was evaluated to classify patients and healthy subjects. Finally, the PET abnormalities were exploratory compared with the patients' characteristics and functional complaints. RESULTS: In comparison to healthy subjects, patients with long COVID exhibited bilateral hypometabolism in the bilateral rectal/orbital gyrus, including the olfactory gyrus; the right temporal lobe, including the amygdala and the hippocampus, extending to the right thalamus; the bilateral pons/medulla brainstem; the bilateral cerebellum (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected). These metabolic clusters were highly discriminant to distinguish patients and healthy subjects (100% correct classification). These clusters of hypometabolism were significantly associated with more numerous functional complaints (brainstem and cerebellar clusters), and all associated with the occurrence of certain symptoms (hyposmia/anosmia, memory/cognitive impairment, pain and insomnia) (p < 0.05). In a more preliminary analysis, the metabolism of the frontal cluster which included the olfactory gyrus was worse in the 7 patients treated by ACE drugs for high blood pressure (p = 0.032), and better in the 3 patients that had used nasal decongestant spray at the infectious stage (p < 0.001). CONCLUSION: This study demonstrates a profile of brain PET hypometabolism in long COVID patients with biologically confirmed SARS-CoV-2 and persistent functional complaints more than 3 weeks after the initial infection symptoms, involving the olfactory gyrus and connected limbic/paralimbic regions, extended to the brainstem and the cerebellum. These hypometabolisms are associated with patients' symptoms, with a biomarker value to identify and potentially follow these patients. The hypometabolism of the frontal cluster, which included the olfactory gyrus, seems to be linked to ACE drugs in patients with high blood pressure, with also a better metabolism of this olfactory region in patients using nasal decongestant spray, suggesting a possible role of ACE receptors as an olfactory gateway for this neurotropism.


Subject(s)
COVID-19 , Fluorodeoxyglucose F18 , Brain/diagnostic imaging , COVID-19/complications , Humans , Positron-Emission Tomography , Retrospective Studies , SARS-CoV-2
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