Project description:Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache, neuroinflammatory or cerebrovascular disease. These conditions - here termed Neuro-COVID - are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared to patients with non-inflammatory and autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells. Neuro-COVID CSF leukocytes featured an enriched interferon signature; however, this was less pronounced than in viral encephalitis. Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in severe compared to mild Neuro-COVID patients. Collectively, our findings document the CSF immune compartment in Neuro-COVID patients and suggest compromised antiviral responses in this setting.
Project description:Background:In the Corona Virus Disease 2019 (COVID-19) pandemic, the primary problem is respiratory-related, but there also is increasing evidence of central nervous system (CNS) involvement. This study aims to summarize the literature on neurological manifestations of COVID-19, underlying mechanisms of CNS involvement and cognitive consequences. Methods:A scoping review was conducted with multiple searches in PubMed, PsycInfo, and CINAHL databases. Full text articles in English were included if they involved humans with COVID-19. The search was updated twice, the latest on 19 May 2020. Results:After screening 266 records and cross referencing, 85 articles were included. The articles were case studies, opinion papers, letters to editors, and a few observational studies. No articles were found regarding cognitive consequences in COVID-19 patients. All reported on neurological manifestations and/or underlying mechanisms of CNS involvement in COVID-19. Conclusion:Neurological manifestations of COVID-19 vary from mild (e.g. loss of taste and smell, dizziness, headache) to severe (e.g. ischemic stroke, encephalitis). Underlying pathways are suggested to be both indirect (as a result of thrombotic complication, inflammatory consequences, hypoxia, blood pressure dysregulation), and direct (neurotropic properties of the virus). Since most articles were opinion papers and no studies have been conducted on cognitive consequences, further research is warranted.
Project description:The COVID-19 pandemic has introduced a global public health threat unparalleled in our history. The most severe cases are marked by ARDS attributed to microvascular thrombosis. Hypercoagulability, resulting in a profoundly prothrombotic state, is a distinct feature of COVID-19 and is accentuated by a high incidence of fibrinolysis shutdown. The aims of this review were to describe the manifestations of fibrinolysis shutdown in COVID-19 and its associated outcomes, review the molecular mechanisms of dysregulated fibrinolysis associated with COVID-19, and discuss potential implications and therapeutic targets for patients with severe COVID-19.
Project description:A spectrum of neurological disease associated with COVID-19 is becoming increasingly apparent. However, the mechanisms behind these manifestations remain poorly understood, significantly hindering their management. The present review subsequently attempts to address the evolving molecular, cellular and systemic mechanisms of NeuroCOVID, which we have classified as the acute and long-term neurological effects of COVID-19. We place particular emphasis on cerebrovascular, demyelinating and encephalitic presentations, which have been reported. Several mechanisms are presented, especially the involvement of a "cytokine storm". We explore the genetic and demographic factors that may predispose individuals to NeuroCOVID. The increasingly evident long-term neurological effects are also presented, including the impact of the virus on cognition, autonomic function and mental wellbeing, which represent an impending burden on already stretched healthcare services. We subsequently reinforce the need for cautious surveillance, especially for those with predisposing factors, with effective clinical phenotyping, appropriate investigation and, if possible, prompt treatment. This will be imperative to prevent downstream neurological sequelae, including those related to the long COVID phenotypes that are being increasingly recognised.
Project description:La COVID-19 peut comporter des troubles neurologiques qui se partagent en 5 grands groupes : des encéphalopathies, souvent avec agitation, confusion, troubles psychotiques, dont la physiopathogénie est sans doute multiple (syndrome inflammatoire général lié au sepsis, hypoxie, insuffisance rénale, hypercoagulabilité, agression directe du virus) ; des syndromes dysimmunitaires du système nerveux central (encéphalomyélites aiguës disséminées, plus rarement syndrome de Miller–Fisher, encéphalite aiguë nécrosante hémorragique…) ; des AVC, majoritairement ischémiques, dont la COVID-19 est un facteur de risque indépendant, probablement par des phénomènes d’hypercoagulabilité ; des syndromes de Guillain–Barré ; des atteintes diverses de nerfs crâniens ou des nerfs périphériques. L’anosmie, qui est très fréquente, est le plus souvent due à une atteinte de l’épithélium olfactif mais peut être due à une extension de l’agression virale au nerf et au cortex olfactifs. Des études complémentaires restent nécessaires pour mieux comprendre la physiopathogénie et, donc, la prévention et le traitement de ces complications neurologiques dues à la COVID-19.
Project description:The aim of the study is to investigate the effects of serum from COVID-19 patients on pluripotent stem cells derived cardiomyocytes (PSC-CMs)
Project description:Acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection continues to be a worldwide public health crisis. Among the several severe manifestations of this disease, thrombotic processes drive the catastrophic organ failure and mortality in these patients. In addition to a well-established cytokine storm associated with the disease, perturbations in platelets, endothelial cells, and the coagulation system are key in triggering systemic coagulopathy, involving both the macro- and microvasculatures of different organs. Of the several mechanisms that might contribute to dysregulation of these cells following SARS-CoV-2 infection, the current review focuses on the role of activated Janus kinase (JAK) signaling in augmenting thrombotic processes and organ dysfunction. The review concludes with presenting the current understanding and emerging controversies concerning the potential therapeutic applications of JAK inhibitors for ameliorating the inflammation-thrombosis phenotype in COVID-19 patients.
Project description:The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic in the last year. Along with major respiratory distress, a myriad of neurological manifestations was also reported to be associated with COVID-19 patients. These cases indicate that SARS-CoV-2 can be considered as an opportunistic pathogen of the brain. SARS-CoV-2 enters the brain through the olfactory bulb, retrograde axonal transport from peripheral nerve endings, or via hematogenous or lymphatic routes. Notably, COVID-19 infection can cause or even present with different neurological features including encephalopathy, impaired consciousness, confusion, agitation, seizure, ataxia, headache, anosmia, ageusia, neuropathies, and neurodegenerative diseases. In this paper, we provide a brief review of observed neurological manifestations associated with COVID-19.