COVID as a potential risk factor for sensorineural hearing loss in newborns

Currently, numerous studies around the world are performed to investigate possible com-plications of COVID-19. Audiovestibular system damage can be a manifestation of a SARS-CoV-2 infection. Various viruses are known to cause congenital hearing impairment. Are neonates of SARS-CoV-2 positive mothers in a risk group of congenital hearing loss? Review of literature is not conclusive, but there is more evidence for COVID-19 not being a risk factor for congenital hearing loss. Limited cohort studies, using newborn hearing screening, were performed to compare the incidence of neonatal hearing loss with newborns with no potential risk factors. More studies are needed to support these results and regular checkups of newborns in a risk of hearing impairment due to maternal SARS-CoV-2 infection to inves-tigate possible complications.

A year in review: brain barriers and brain fluids research in 2022.

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

Human brain organoids to explore SARS-CoV-2-induced effects on the central nervous system.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). In less than three years, an estimated 600 million infections with SARS-CoV-2 occurred worldwide, resulting in a pandemic with tremendous impact especially on economic and health sectors. Initially considered a respiratory disease, COVID-19, along with its long-term sequelae (long-COVID) rather is a systemic disease. Neurological symptoms like dementia or encephalopathy were reported early during the pandemic as concomitants of the acute phase and as characteristics of long-COVID. An excessive inflammatory immune response is hypothesized to play a major role in this context. However, direct infection of neural cells may also contribute to the neurological aspects of (long)-COVID-19. To mainly explore such direct effects of SARS-CoV-2 on the central nervous system, human brain organoids provide a useful platform. Infecting these three-dimensional tissue cultures allows the study of viral neurotropism as well as of virus-induced effects on single cells or even the complex cellular network within the organoid. In this review, we summarize the experimental studies that used SARS-CoV-2-infected human brain organoids to unravel the complex nature of (long)-COVID-19-related neurological manifestations.

Choroid Plexus Papilloma in a Adult: Case Report

Purpose: Chroroid plexus tumours are a rare intraventricular neoplasm originating from choroid plexus that account for only 0.3-0.6% of all intracranial tumours. These tumours are seen more frequently in children, especially in first two years of life with an incidence of 1.5-4% in this age group. The mayority of the tumours are benign choroid plexus papilloma WHO Grade I. Here we report a case of choroid plexus papilloma in an adult patient and his treatment. Material(s) and Method(s): A 39-year-old man was admitted to the neurosurgery department of his hospital for a headache, gaze shift to the left, and disorientation. By computed tomography and magnetic resonance imaging in January / 2020, a tumour in the third ventricle directed to the mesencephalon with a cystic component was reported compatible with choroid plexus papilloma of 21x26x22mm. Due to the location and restriction of surgical treatments due to the COVID19 pandemic, he was sent for radiotherapy evaluation. Treatment with stereotactic radiosurgery was decided in our department 12 Gy in 1 fraction in a volume at PTV of 11.25cc with a prescription at 100% of the dose, coverage of 98.3% at GTV in 31th July 2020. Surveillance was maintained through imaging studies. Result(s): By magnetic resonance imaging of July 23, 2021, 12 months after having indicated the treatment, no tumour data was reported, although clinically even with mild persistence of dizziness, achieving a complete answer. Conclusion(s): Choroid plexus papillomas are rare, benign tumours originating from choroid plexus. Although its initial treatment has been established surgical resection, it cannot always be achieved due to the location, conditions of the patient, or in this case indirect reasons such as space limitation due to Pandemic. In this case, radiosurgery was indicated as initial treatment, achieving a complete response at 12 months, so we verified that radiosurgery can be used as initial treatment in early stages and in locations that are not susceptible to resection Copyright © 2022 Elsevier Ireland Ltd. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Pathomorphological changes in some organs and tissues of COVID-19 convalescent patients

New coronavirus infection (COVID-19) is highly contagious viral disease caused by SARS-CoV-2 leading to the pandemic. The autopsy of COVID-19 patients often showed features of previous brain diseases including neurodegeneration, previous strokes, demyelinating diseases and atherosclerosis. Patients with acute cerebrovascular accidents and severe COVID-19 had higher numbers of lethality in comparison to non-severe course of infection without cerebrovascular accidents. A comparative analysis of morphological changes in lungs of deceased patients who died in different periods of first clinical symptoms is to be conducted. Objective. Description of pathomorphological changes in deceased patients during the period of reconvalescence. Patients and methods. The analysis of 15 fatal cases which took place in Botkin Hospital with the diagnosis of ischemic stroke and new coronavirus infection in the previous 2-4 months has been held. Macro and microscope examination of brain, lungs, brachiocephalic arteries, kidneys and liver has been carried out. Results. All patients had morphological features of ischemic damage of grey matter in the brain. Beside necrosis of neurocytes with diffuse infiltration in the grey matter, hematoxylin cycles were found, in some cases they were placed in a perivascular way in choroid plexus. Also 5 patients suffered a myocardial infarction up to 3 days. 10 patients had structures disorganisation in areas of lung parenchyma with hystoacrchitectonic changes because of the fibrosis. Alveoli in some places collaborated mostly with single airway clearance. The fact that most patients had lung hemosiderosis can prove coronavirus infection suffered earlier with microcirculatory bed damage. Conclusion. Thus, morphological changes seen in the period of reconvalescence of COVID-19 is a result of pathomorphosis of changes described earlier for acute period of coronavirus infection and affect not only lungs, but also other organs and tissues. This proves systematic characteristic of the infection.

The choroid plexus and its role in the pathogenesis of neurological infections.

The choroid plexus is situated at an anatomically and functionally important interface within the ventricles of the brain, forming the blood-cerebrospinal fluid barrier that separates the periphery from the central nervous system. In contrast to the blood-brain barrier, the choroid plexus and its epithelial barrier have received considerably less attention. As the main producer of cerebrospinal fluid, the secretory functions of the epithelial cells aid in the maintenance of CNS homeostasis and are capable of relaying inflammatory signals to the brain. The choroid plexus acts as an immunological niche where several types of peripheral immune cells can be found within the stroma including dendritic cells, macrophages, and T cells. Including the epithelia cells, these cells perform immunosurveillance, detecting pathogens and changes in the cytokine milieu. As such, their activation leads to the release of homing molecules to induce chemotaxis of circulating immune cells, driving an immune response at the choroid plexus. Research into the barrier properties have shown how inflammation can alter the structural junctions and promote increased bidirectional transmigration of cells and pathogens. The goal of this review is to highlight our foundational knowledge of the choroid plexus and discuss how recent research has shifted our understanding towards viewing the choroid plexus as a highly dynamic and important contributor to the pathogenesis of neurological infections. With the emergence of several high-profile diseases, including ZIKA and SARS-CoV-2, this review provides a pertinent update on the cellular response of the choroid plexus to these diseases. Historically, pharmacological interventions of CNS disorders have proven difficult to develop, however, a greater focus on the role of the choroid plexus in driving these disorders would provide for novel targets and routes for therapeutics.

Potential Neuroinvasion Mechanism of SARS-CoV-2

The severe acute respiratory syndrome coronavirus-2, a coronavirus, is known to cause acute respiratory distress syndrome and a range of non)respiratory effects, particularly in elderly male patients with underlying health conditions such overweight, diabetes, and hypertension. The coronavirus disease-2019 sequelae include multiple organ failure and neurological issues, and these prior health issues are linked to endothelial dysfunction. Although inhalation is the most frequent mode of infection, this virus has also been discovered in neurons, cerebrospinal fluid, the choroid plexus, and meningeal vasculature (English) [ FROM AUTHOR] Bir koronavirüs olan şiddetli akut solunum yolu sendromu koronavirüsü-2’nin, özellikle obezite, diyabet ve hipertansiyon gibi sağlık sorunları olan yaşlı erkek hastalarda akut solunum sıkıntısı sendromuna ve bir dizi solunum dışı sekellere neden olduğu bilinmektedir. Bu sağlık sorunları endotel disfonksiyonla bağlantılıdır ve koronavirüs hastalığı-2019 sekelleri, çoklu organ yetmezliği ve nörolojik sorunları içerir. Solunum birincil enfeksiyon modu olsa da, bu virüs koroid pleksus ve meningeal arterlerin yanı sıra nöronlar ve beyin omurilik sıvısı dahil olmak üzere çeşitli organlarda keşfedilmiştir (Turkish) [ FROM AUTHOR] Copyright of Turkish Journal of Immunology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Retrograde cerebral air embolism in a patient on venovenous ECMO

INTRODUCTION: Retrograde cerebral air embolism (CAE) is rarely described in literature that may be associated with manipulation of central or peripheral venous catheters. During a literature review, there were no described occurrences of CAE in patients on veno-venous (V-V) ECMO. DESCRIPTION: A 42-year-old male with ARDS secondary to COVID-19 pneumonitis was cannulated for V-V ECMO outside our facility and transferred to our cardiovascular intensive care unit. Upon arrival, he was noted to have a right femoral drainage cannula and right internal jugular (RIJ) venous antegrade cannula. On day 10 of his hospital stay he was converted to a RIJ Protek duo cannula and the right femoral drainage cannula was removed. This cannula was repositioned multiple times after placement due to flow issues. Due to poor oxygenator membrane function, it became necessary to exchange the oxygenator on day 25. During the exchange, the patient experienced sudden-onset bradycardia that progressed to several seconds of asystole. He regained spontaneous cardiac activity after a bolus dose of IV glycopyrrolate. Following this, he had several episodes of bradycardia and eventually asystole that resolved after one round of ACLS and IV atropine. The bradycardic episodes continued after this event and were associated with hypertension. On day 25, the patient suffered a decline in neurologic status from a GCS of 11T to 3T. The patient was sent emergently for non-contrast CT head. This scan revealed pneumocephalus with diffuse foci of air emboli in the subarachnoid and intraventricular spaces, the choroid plexus, and dural venous sinuses. After a family discussion, care was withdrawn from the patient on day 27. DISCUSSION: This patient suffered a massive retrograde CAE peri-ECMO circuit oxygenator exchange. It is our understanding that this a novel clinical situation for this phenomenon and not previously described in literature. This emphasizes that manipulation of any vascular cannula may result in the entrainment of air in a retrograde venous fashion into the cerebral vasculature.

SARS-CoV-2 infection of the central nervous system in a 14-month-old child: A case report of a complete autopsy.

BACKGROUND: Neurological and other systemic complications occur in adults with severe COVID-19. Here we describe SARS-CoV-2 infection complicated by neuroinvasion in the post-mortem tissues of a child. METHODS: We performed a complete autopsy of a 14-month-old child who died of COVID-19 pneumonitis. Histological sections of multiple organs were stained with haematoxylin and eosin. Luxol fast blue staining for myelin and immunohistochemistry were performed in selected areas of the brain. The presence of SARS-CoV-2 was investigated by immunostaining with anti-spike protein antibody and by RT-qPCR. FINDINGS: Lesions included microthrombosis, pulmonary congestion, interstitial oedema, lymphocytic infiltrates, bronchiolar injury, collapsed alveolar spaces, cortical atrophy, and severe neuronal loss. SARS-CoV-2 staining was observed along the apical region of the choroid plexus (ChP) epithelium and in ependymal cells of the lateral ventricle, but was restricted to ChP capillaries and vessels in some regions. SARS-CoV-2 infection of brain tissue was confirmed by RT-qPCR in fragments of the ChP, lateral ventricle, and cortex. INTERPRETATION: Our results show multisystemic histopathological alterations caused by SARS-CoV-2 infection and contribute to knowledge regarding the course of fatal COVID-19 in children. Furthermore, our findings of ChP infection and viral neurotropism suggest that SARS-CoV-2 may invade the central nervous system by blood-cerebrospinal fluid barrier disruption. FUNDING: Carlos Chagas Filho Foundation for Supporting Research in the State of Rio de Janeiro (FAPERJ); the National Council for Scientific and Technological Development (CNPq) and Coordination for the Improvement of Higher Education Personnel (CAPES), in addition to intramural grants from D'Or Institute for Research and Education. EDITOR'S NOTE: This translation in Portuguese was submitted by the authors and we reproduce it as supplied. It has not been peer reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as reference for this manuscript. RESUMO: Complicações sistêmicas e neurológicas foram descritas em adultos com COVID-19 grave. Neste trabalho, descrevemos a infecção por SARS-CoV-2, incluindo sua neuroinvasão, nos tecidos post-mortem de uma criança. MÉTODOS: Realizamos a autópsia completa de uma criança de 14 meses que morreu de pneumonite por COVID-19. Cortes histológicos de múltiplos órgãos foram corados com Hematoxilina e Eosina. A coloração de Luxol Fast Blue para mielina e imuno-histoquímica foram realizadas em áreas selecionadas do cérebro. A presença de SARS-CoV-2 foi investigada por imunomarcação com anticorpo anti-proteína spike e por RT-qPCR. ACHADOS: As lesões incluíram microtrombose, congestão pulmonar, edema intersticial, infiltrados linfocíticos, lesão bronquiolar, colapso dos espaços alveolares, atrofia cortical e perda neuronal grave. A presença de SARS-CoV-2 foi observada ao longo da região apical do epitélio do plexo coróide (PC) e nas células ependimárias do ventrículo lateral, mas ficou restrita aos capilares e vasos do PC em outras regiões. A infecção do tecido cerebral por SARS-CoV-2 foi confirmada por RT-qPCR em fragmentos do PC, ventrículo lateral e cortex cerebral. INTERPRETAÇÃO: Nossos resultados mostram alterações histopatológicas multissistêmicas causadas pela infecção por SARS-CoV-2 e contribuem para ampliar o conhecimento sobre a evolução da COVID-19 fatal em crianças. Além disso, nossos achados sobre a infecção no PC e neurotropismo viral sugerem que o SARS-CoV-2 pode invadir o sistema nervoso central pela ruptura da barreira sangue-líquido cefalorraquidiano. FINANCIAMENTO: Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ) e Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), além de financiamento intramural do Instituto D'Or de Pesquisa e Educação.

Single-nucleus transcriptome analysis of human brain immune response in patients with severe COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been associated with neurological and neuropsychiatric illness in many individuals. We sought to further our understanding of the relationship between brain tropism, neuro-inflammation, and host immune response in acute COVID-19 cases. METHODS: Three brain regions (dorsolateral prefrontal cortex, medulla oblongata, and choroid plexus) from 5 patients with severe COVID-19 and 4 controls were examined. The presence of the virus was assessed by western blot against viral spike protein, as well as viral transcriptome analysis covering > 99% of SARS-CoV-2 genome and all potential serotypes. Droplet-based single-nucleus RNA sequencing (snRNA-seq) was performed in the same samples to examine the impact of COVID-19 on transcription in individual cells of the brain. RESULTS: Quantification of viral spike S1 protein and viral transcripts did not detect SARS-CoV-2 in the postmortem brain tissue. However, analysis of 68,557 single-nucleus transcriptomes from three distinct regions of the brain identified an increased proportion of stromal cells, monocytes, and macrophages in the choroid plexus of COVID-19 patients. Furthermore, differential gene expression, pseudo-temporal trajectory, and gene regulatory network analyses revealed transcriptional changes in the cortical microglia associated with a range of biological processes, including cellular activation, mobility, and phagocytosis. CONCLUSIONS: Despite the absence of detectable SARS-CoV-2 in the brain at the time of death, the findings suggest significant and persistent neuroinflammation in patients with acute COVID-19.

SARS-CoV-2: is there neuroinvasion?

BACKGROUND: SARS-CoV-2, a coronavirus (CoV), is known to cause acute respiratory distress syndrome, and a number of non-respiratory complications, particularly in older male patients with prior health conditions, such as obesity, diabetes and hypertension. These prior health conditions are associated with vascular dysfunction, and the CoV disease 2019 (COVID-19) complications include multiorgan failure and neurological problems. While the main route of entry into the body is inhalation, this virus has been found in many tissues, including the choroid plexus and meningeal vessels, and in neurons and CSF. MAIN BODY: We reviewed SARS-CoV-2/COVID-19, ACE2 distribution and beneficial effects, the CNS vascular barriers, possible mechanisms by which the virus enters the brain, outlined prior health conditions (obesity, hypertension and diabetes), neurological COVID-19 manifestation and the aging cerebrovascualture. The overall aim is to provide the general reader with a breadth of information on this type of virus and the wide distribution of its main receptor so as to better understand the significance of neurological complications, uniqueness of the brain, and the pre-existing medical conditions that affect brain. The main issue is that there is no sound evidence for large flux of SARS-CoV-2 into brain, at present, compared to its invasion of the inhalation pathways. CONCLUSIONS: While SARS-CoV-2 is detected in brains from severely infected patients, it is unclear on how it gets there. There is no sound evidence of SARS-CoV-2 flux into brain to significantly contribute to the overall outcomes once the respiratory system is invaded by the virus. The consensus, based on the normal route of infection and presence of SARS-CoV-2 in severely infected patients, is that the olfactory mucosa is a possible route into brain. Studies are needed to demonstrate flux of SARS-CoV-2 into brain, and its replication in the parenchyma to demonstrate neuroinvasion. It is possible that the neurological manifestations of COVID-19 are a consequence of mainly cardio-respiratory distress and multiorgan failure. Understanding potential SARS-CoV-2 neuroinvasion pathways could help to better define the non-respiratory neurological manifestation of COVID-19.

Hepcidin Increases Cytokines in Alzheimer's Disease and Down's Syndrome Dementia: Implication of Impaired Iron Homeostasis in Neuroinflammation.

The liver-derived hormone hepcidin, a member of the defensin family of antimicrobial peptides, plays an important role in host defense and innate immunity due to its broad antibacterial and antiviral properties. Ferritin, an iron storage protein is often associated with iron deficiency, hypoferritinemia, hypoxia, and immune complications, which are all significant concerns for systemic infection in Alzheimer's disease (AD) and Down's syndrome (DS) dementia. Serum and post-mortem brain samples were collected from AD, DS and age-matched control subjects. Serum samples were analyzed with ELISA for ferritin, hepcidin and IL-6. Additionally, post-mortem brain sections were assessed by immunohistochemistry for iron-related and inflammatory proteins. A significant increase in serum hepcidin levels was found in DS, compared to controls and AD subjects (p < 0.0001). Hepcidin protein was visible in the epithelial cells of choroid plexus, meningeal macrophages and in the astrocytes close to the endothelium of blood vessels. Hepcidin co-localized with IL-6, indicating its anti-inflammatory properties. We found significant correlation between hypoferritinemia and elevated levels of serum hepcidin in AD and DS. Hepcidin can be transported via macrophages and the majority of the vesicular hepcidin enters the brain via a compromised blood brain barrier (BBB). Our findings provide further insight into the molecular implications of the altered iron metabolism in acute inflammation, and can aid towards the development of preventive strategies and novel treatments in the fight against neuroinflammation.

Histological Evidence for the Enteric Nervous System and the Choroid Plexus as Alternative Routes of Neuroinvasion by SARS-CoV2.

Evidence is mounting that the novel corona virus SARS-CoV2 inflicts neurological symptoms in a subgroup of COVID-19 patients. While plenty of theories on the route of neuroinvasion have been proposed, little histological evidence has been presented supporting any of these hypotheses. Therefore, we carried out immunostainings for ACE2 and TMPRSS2, two proteinases crucial for the entry of SARS-CoV2 into host cells, in the human enteric nervous system (ENS), as well as in the choroid plexus of the lateral ventricles. Both of these sites are important, yet often neglected entry gates to the nervous system. We found that ACE2 and TMPRSS2 are expressed by enteric neurons and glial cells of the small and large intestine, as well as choroid plexus epithelial cells, indicating that these cells meet the molecular requirements for viral entry. Together, our results are fundamental histological evidence substantiating current theories of neuroinvasion by SARS-CoV2.

SARS-CoV-2 Infects the Brain Choroid Plexus and Disrupts the Blood-CSF Barrier in Human Brain Organoids.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, leads to respiratory symptoms that can be fatal. However, neurological symptoms have also been observed in some patients. The cause of these complications is currently unknown. Here, we use human-pluripotent-stem-cell-derived brain organoids to examine SARS-CoV-2 neurotropism. We find expression of viral receptor ACE2 in mature choroid plexus cells expressing abundant lipoproteins, but not in neurons or other cell types. We challenge organoids with SARS-CoV-2 spike pseudovirus and live virus to demonstrate viral tropism for choroid plexus epithelial cells but little to no infection of neurons or glia. We find that infected cells are apolipoprotein- and ACE2-expressing cells of the choroid plexus epithelial barrier. Finally, we show that infection with SARS-CoV-2 damages the choroid plexus epithelium, leading to leakage across this important barrier that normally prevents entry of pathogens, immune cells, and cytokines into cerebrospinal fluid and the brain.

Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium.

Neurological complications are common in patients with COVID-19. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal pathogen of COVID-19, has been detected in some patient brains, its ability to infect brain cells and impact their function is not well understood. Here, we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found that neurons and astrocytes were sparsely infected, but choroid plexus epithelial cells underwent robust infection. We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our findings provide evidence for selective SARS-CoV-2 neurotropism and support the use of hiPSC-derived brain organoids as a platform to investigate SARS-CoV-2 infection susceptibility of brain cells, mechanisms of virus-induced brain dysfunction, and treatment strategies.