Mixed central and peripheral nervous system disorders in severe SARS-CoV-2 infection.
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ABSTRACT:
SUBMITTER: Chaumont H
PROVIDER: S-EPMC7292244 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
Mixed central and peripheral nervous system disorders in severe SARS-CoV-2 infection.
Chaumont H H San-Galli A A Martino F F Couratier C C Joguet G G Carles M M Roze E E Lannuzel A A
Journal of neurology 20200612 11
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Project description:BackgroundCancer patients may be at higher risk for severe coronavirus infectious disease-19 (COVID-19); however, the outcome of Primary Central Nervous System Lymphoma (PCNSL) patients with SARS-CoV-2 infection has not been described yet.MethodsWe conducted a retrospective study within the Lymphomes Oculo-Cérébraux national network (LOC) to assess the clinical characteristics and outcome of SARS-CoV-2 infection in PCNSL patients (positive real-time polymerase chain reaction of nasopharyngeal swab or evocative lung computed tomography scan). We compared clinical characteristics between patients with severe (death and/or intensive care unit admission) and mild disease.ResultsBetween March and May 2020, 13 PCNSL patients were diagnosed with SARS-CoV-2 infection, 11 (85%) of whom were undergoing chemotherapy at the time of infection. The mortality rate was 23% (3/13), and two additional patients (15%) required mechanical ventilation. Two patients (15%) had no COVID-19 symptoms. History of diabetes mellitus was more common in severe patients (3/5 vs 0/8, p = 0.03). Two patients recovered from COVID-19 after mechanical ventilation during more than two weeks and resumed chemotherapy. In all, chemotherapy was resumed after COVID-19 recovery in nine patients (69%) after a median delay of 16 days (range 3-32), none of whom developed unusual chemotherapy complication nor SARS-Cov2 reactivation.ConclusionThis preliminary analysis suggests that, while being at higher risk be for severe illness, PCNSL patients with COVID-19 might be treated maximally especially if they achieved oncological response at the time of SARS-CoV-2 infection. Chemotherapy might be resumed without prolonged delay in PCNSL patients with COVID-19.
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Project description:Coronaviruses belong to a well-known family of enveloped RNA viruses and the causative agent of the common cold. Although the seasonal coronaviruses do not pose a threat to human life, three members of this family, i.e., SARS-CoV, MERS-CoV and recently, SARS-CoV2, may cause severe acute respiratory syndrome that may lead to death. Unfortunately, COVID-19 has already caused more than 4,4 million deaths worldwide. Although much is better understood about the immunopathogenesis of the lung disease, important information about systemic disease is still missing, mainly concerning neurological parameters. In this context, we sought to evaluate immunometabolic changes using in vitro and in vivo models of hamsters infected with SARS-CoV2. Here show that, besides infecting and replicating in glial cells, SARS-CoV2 induces important changes in protein expression and metabolic pathways, specially involved in carbon metabolism, glycolysis, and mitochondrial respiration. Interestingly, many of the differentially expressed proteins during SARS-CoV2 infection overlapped with proteins correlated with neurological diseases, such as Parkinsons's Disease, multiple sclerosis, amyotrophic lateral sclerosis and Huntington's disease. Metabolic analysis by high resolution real-time respirometry evidenced hyperactivation of glycolysis and mitochondrial respiration, which was confirmed by metabolomics. Brain infection with SARS-CoV2 was confirmed in vivo as hippocampus, cortex and olfactory bulb of infected hamsters were positive for viral genome both at 4 and 7 days post-infection. Unexpectedly, we observed that glutamine was significantly reduced in mixed glial cells infected with SARS-CoV2 and that the blockade of glutaminolysis significantly reduced viral replication and pro-inflammatory response. Altogether, our data confirms the infection of brain cells by SARS-CoV2 but, most importantly, there is an important change in overall protein expression profile, mostly of proteins related to metabolic pathways. This may suggest that some of the neurological impairments observed during COVID-19, as the brain fog and cognitive impairment, may rely on altered protein expression and unbalanced glutamine/glutamate levels, whose importance for adequate brain function is unquestionable.
2022-09-28 | PXD029426 | Pride
Project description:IntroductionThe response to the SARS-CoV-2 coronavirus epidemic requires increased research efforts to expand our knowledge of the disease. Questions related to infection rates and mechanisms, the possibility of reinfection, and potential therapeutic approaches require us not only to use the experimental models previously employed for the SARS-CoV and MERS-CoV coronaviruses but also to generate new models to respond to urgent questions.DevelopmentWe reviewed the different experimental models used in the study of central nervous system (CNS) involvement in COVID-19 both in different cell lines that have enabled identification of the virus' action mechanisms and in animal models (mice, rats, hamsters, ferrets, and primates) inoculated with the virus. Specifically, we reviewed models used to assess the presence and effects of SARS-CoV-2 on the CNS, including neural cell lines, animal models such as mouse hepatitis virus CoV (especially the 59 strain), and the use of brain organoids.ConclusionGiven the clear need to increase our understanding of SARS-CoV-2, as well as its potential effects on the CNS, we must endeavor to obtain new information with cellular or animal models, with an appropriate resemblance between models and human patients.
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Project description:C1q is a crucial component of the complement system, which is activated through the classical pathway to perform non-specific immune functions, serving as the first line of defense against pathogens. C1q can also bind to specific receptors to carry out immune and other functions, playing a vital role in maintaining immune homeostasis and normal physiological functions. In the developing central nervous system (CNS), C1q functions in synapse formation and pruning, serving as a key player in the development and homeostasis of neuronal networks in the CNS. C1q has a close relationship with microglia and astrocytes, and under their influence, C1q may contribute to the development of CNS disorders. Furthermore, C1q can also have independent effects on neurological disorders, producing either beneficial or detrimental outcomes. Most of the evidence for these functions comes from animal models, with some also from human specimen studies. C1q is now emerging as a promising target for the treatment of a variety of diseases, and clinical trials are already underway for CNS disorders. This article highlights the role of C1q in CNS diseases, offering new directions for the diagnosis and treatment of these conditions.
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Project description:Zinc (Zn2+) is the second most abundant necessary trace element in the human body, exerting a critical role in many physiological processes such as cellular proliferation, transcription, apoptosis, growth, immunity, and wound healing. It is an essential catalyst ion for many enzymes and transcription factors. The maintenance of Zn2+ homeostasis is essential for the central nervous system, in which Zn2+ is abundantly distributed and accumulates in presynaptic vesicles. Synaptic Zn2+ is necessary for neural transmission, playing a pivotal role in neurogenesis, cognition, memory, and learning. Emerging data suggest that disruption of Zn2+ homeostasis is associated with several central nervous system disorders including Alzheimer's disease, depression, Parkinson's disease, multiple sclerosis, schizophrenia, epilepsy, and traumatic brain injury. Here, we reviewed the correlation between Zn2+ and these central nervous system disorders. The potential mechanisms were also included. We hope that this review can provide new clues for the prevention and treatment of nervous system disorders.
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Project description:Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the recent global COVID-19 outbreak, which led to a public health emergency. Entry of SARS-CoV-2 into human cells is dependent on the SARS-CoV receptor, angiotensin converting enzyme 2 (ACE2) receptor, and cathepsin. Cathepsin degrades the spike protein (S protein), which results in the entry of viral nucleic acid into the human host cell. Methods: We explored the susceptibility of the central nervous system (CNS) to SARS-CoV-2 infection using single-cell transcriptome analysis of glioblastoma. Results: The results showed that ACE2 expression is relatively high in endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and neural precursor cells (NPCs). Cathepsin B (Cat B) and cathepsin (Cat L) were also strongly expressed in various cell clusters within the glioblastoma microenvironment. Immunofluorescence staining of glioma and normal brain tissue chips further confirmed that ACE2 expression co-localized with CD31, CD73, and nestin, which confirmed the susceptibility to SARS-CoV-2 of nervous system cells, including ECs, BMSCs and NPCs, from clinical specimens. Conclusions: These findings reveal the mechanism of SARS-CoV-2 neural invasion and suggest that special attention should be paid to SARS-CoV-2-infected patients with neural symptoms, especially those who suffered a glioma.
2020-11-12 | GSE157424 | GEO
Project description:As a severe and highly contagious infectious disease, coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several case reports have demonstrated that the respiratory system is the main target in patients with COVID-19, but the disease is not limited to the respiratory system. Case analysis indicated that the nervous system can be invaded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that 36.4% of COVID-19 patients had neurological symptoms. Importantly, the involvement of the CNS may be associated with poor prognosis and disease worsening. Here, we discussed the symptoms and evidence of nervous system involvement (directly and indirectly) caused by SARS-CoV-2 infection and possible mechanisms. CNS symptoms could be a potential indicator of poor prognosis; therefore, the prevention and treatment of CNS symptoms are also crucial for the recovery of COVID-19 patients.
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Project description:SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induces the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted to the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions that share a high identity between SARS-CoV-2 antigens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG, and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals.
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Project description:ObjectivesInfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Although an acute SARS-CoV-2 infection mainly presents with respiratory illness, neurologic symptoms and sequelae are increasingly recognised in the long-term treatment of COVID-19 patients. The pathophysiology and the neuropathogenesis behind neurologic complications of COVID-19 remain poorly understood, but mounting evidence points to endothelial dysfunction either directly caused by viral infection or indirectly by inflammatory cytokines, followed by a local immune response that may include virus-specific T cells. However, the type and role of central nervous system-infiltrating T cells in COVID-19 are complex and not fully understood.MethodsWe analysed distinct anatomical brain regions of patients who had deceased as a result of COVID-19-associated pneumonia or complications thereof and performed T cell receptor Vβ repertoire sequencing. Clonotypes were analysed for SARS-CoV-2 association using public TCR repertoire data.ResultsOur descriptive study demonstrates that SARS-CoV-2-associated T cells are found in almost all brain areas of patients with fatal COVID-19 courses. The olfactory bulb, medulla and cerebellum were brain regions showing the most SARS-CoV-2 specific sequence patterns. Neuropathological workup demonstrated primary CD8+ T-cell infiltration with a perivascular infiltration pattern.ConclusionFuture research is needed to better define the relationship between T-cell infiltration and neurological symptoms and its long-term impact on patients' cognitive and mental health.
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