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SARS-CoV-2 proteins

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    Neuron Signal Propagation Analysis of Cytokine-Storm induced Demyelination MESHD

    Authors: Geoflly L. Adonias; Harun Siljak; Michael Taynnan Barros; Sasitharan Balasubramaniam

    id:2103.03790v1 Date: 2021-03-05 Source: arXiv

    The COVID-19 pandemic MESHD has shaken the world unprecedentedly, where it has affected the vast global population both socially and economically. The pandemic has also opened our eyes to the many threats that novel virus infections can pose for humanity. While numerous unknowns are being investigated in terms of the distributed damage that the virus can do to the human body, recent studies have also shown that the infection can lead to lifelong sequelae that could affect other parts of the body, and one example is the brain. As part of this work, we investigate how viral infection can affect the brain by modelling and simulating a neuron's behaviour under demyelination MESHD that is affected by the cytokine storm. We quantify the effects of cytokine-induced demyelination MESHD on the propagation of action potential signals within a neuron. We used information and communication theory analysis on the signal propagated through the axonal pathway under different intensity levels of demyelination MESHD to analyse these effects. Our simulations demonstrate that virus-induced degeneration MESHD can play a role in the signal power and spiking rate and the probability of releasing neurotransmitters and compromising the propagation and processing of information between the neurons. We also propose a transfer function that models these attenuation effects that degenerates the action potential, where this model has the potential to be used as a framework for the analysis of virus-induced neurodegeneration MESHD that can pave the way to improved understanding of virus-induced demyelination MESHD.

    Neuroimaging Features of COVID-19 MESHD: Retrospective Northern Italy Multicenter Study and a Scoping Review of the Prevalence of COVID-19 MESHD Associated Acute Cerebrovascular Diseases MESHD

    Authors: Andrea Giorgianni; Francesco D'Amore; Gabriele Vinacci; Edoardo Agosti; Letterio Politi; Andrea De Vito; Alessandra Polistena; Luca Valvassori; Mirko Trentadue; Lisa Nicoli; Carlo Sozzi; Sergio Balbi; Anna Mercuri; Alberto Terrana; Fabio Triulzi; Casale Silvia; Nunzio Nuzzi; Francesco Asteggiano; Valentina Genovese; Elvis Lafe; Elena Bianchini; Pietro Bernasconi; Enrico Colli-Tibaldi; Laura Longhi; Francesca Bandiera; Fabio Baruzzi

    doi:10.21203/rs.3.rs-150229/v1 Date: 2021-01-18 Source: ResearchSquare

    Background The primary aim of this study was to provide additional data of neuroimaging features of coronavirus disease 2019 MESHD ( COVID-19 MESHD) in a large-scale population admitted in several northern Italy institutions. The secondary aim was to analyze acute cerebrovascular disease MESHD ( CVD MESHD) prevalence in COVID-19 MESHD. Methods A database of confirmed COVID-19 MESHD hospitalized patients who developed acute neurological symptoms MESHD and underwent any neuroimaging was retrospectively gathered from twelve institutions based in Lombardy from February 21st to July 10th. To assess the prevalence of CVD MESHD we conducted a scoping review following the PRISMA extension guidelines for scoping reviews. We searched PubMed/Medline, SCOPUS and EMBASE databases for peer-reviewed in-press or published studies from December to January 2021 reporting CVD MESHD in COVID-19 MESHD patients. Results Out of 90 COVID-19 MESHD patients who were referred to neuroimaging, 78 (87%) showed CVD MESHD, in particular 65 had acute ischemic strokes MESHD (AIS), 8 had intracerebral hemorrhages MESHD, 2 subarachnoid hemorrhages MESHD ( SAH MESHD) and 3 showed clinical and imaging findings in keeping with posterior reversible encephalopathy syndrome MESHD ( PRES MESHD); 6 patients (7%) showed clinical and imaging findings highly suggestive of encephalitis MESHD; 3 patients (3%) showed demyelinating diseases MESHD: 1 case of MS progression, 1 case of newly diagnosed MS MESHD and 1 case of acute disseminated encephalomyelitis MESHD ( ADEM MESHD); 2 cases (2%) acuity of chronic subdural hematoma MESHD ( cSDH MESHD); 1 patient (1%) with Guillain Barré syndrome. In addiction two patients with CVD MESHD developed cauda polyradiculitis and tetraparesis MESHD. In our scoping review out of 3275 studies, 24 satisfied the inclusion criteria: in a pooled total population of 136198 patients, the pooled prevalence of CVD MESHD was 0.9%. In particular 0.8% of AIS MESHD and 0.1% of ICH MESHD and 0.003% of PRES. Conclusions Our study shows a high prevalence of CVD MESHD among patients who developed acute neurological symptoms MESHD, which is in line with papers reporting data comparable to ours. The heterogeneity of clinical reports, however, constitutes a limitation when comparing our findings with those of the clinical papers. Nonetheless, CVD MESHD could be a frightening association with COVID-19 MESHD, particularly in critically ill MESHD patients. Healthcare policymakers and clinicians should be prepared to a likely increase in workload and to rearrange the strategy of healthcare delivery.

    Interferons and Multiple Sclerosis: Lessons from 25 Years of Clinical and Real-World Experience with Intramuscular Interferon-Beta-1a (Avonex)

    Authors: Stanley Cohan; Barry Hendin; Anthony Reder; Kyle Smoot; Robin Avila; Jason Mendoza; Bianca Weinstock-Guttman

    id:202101.0183/v1 Date: 2021-01-11 Source: Preprints.org

    Multiple sclerosis MESHD ( MS MESHD) is a chronic inflammatory demyelinating disease MESHD of the central nervous system. The interferons (IFNs) were discovered in 1957, and recombinant IFN-β-1b was approved by the US Food and Drug Administration as the first disease-modifying therapy (DMT) for MS MESHD in 1993. Since that time, clinical trials and real-world observational studies have demonstrated the effectiveness of IFN HGNC therapies. The pivotal intramuscular IFN-β HGNC-1a phase 3 trial was the first to demonstrate that a DMT could reduce accumulation of sustained disability in MS MESHD. Patient adherence to treatment is higher with intramuscular IFN-β-1a, given once weekly, than with subcutaneous formulations requiring multiple injections per week. Moreover, subcutaneous IFN-β HGNC-1a is associated with an increased incidence of injection site reactions and neutralizing antibodies compared with intramuscular administration. In recent years, revisions to MS MESHD diagnostic criteria have improved clinicians’ ability to identify patients with MS MESHD and have promoted the use of magnetic resonance imaging (MRI) for diagnosis and monitoring. MRI studies show that treatment with IFN-β-1a, relative to placebo, reduces T2 and gadolinium-enhancing lesions and gray matter atrophy MESHD. Since the approval of intramuscular IFN-β-1a, several high-efficacy therapies have been approved for MS MESHD, though the benefit of these high-efficacy therapies should be balanced against the increased risk of serious adverse events. For some subpopulations of patients, including pregnant women, the safety profile of IFN-β HGNC formulations may provide a particular benefit. In addition, the antiviral properties of IFNs may indicate therapeutic opportunities for IFN-β HGNC in the treatment of viral infections such as COVID-19 MESHD.

    Efficacy of vafidemstat in experimental autoimmune encephalomyelitis MESHD highlights the KDM1A/RCOR1/HDAC epigenetic axis in multiple sclerosis MESHD

    Authors: Fernando Cavalcanti; Elena Gonzalez-Rey; Mario Delgado; Leyre Mestre; Carmen Guaza; Michele MP Lufino; Jordi Xaus; Cristina Mascaró; Serena Lunardi; Natalia Sacilotto; Paola Dessanti; David Rotllant; Xavier Navarro; Mireia Herrando-Grabulosa; Carlos Buesa; Tamara Maes

    doi:10.21203/rs.3.rs-114482/v5 Date: 2020-11-23 Source: ResearchSquare

    Background Vafidemstat (ORY-2001) is a clinical stage inhibitor of the Lysine Specific Demethylase KDM1A in development for treatment of neurodegenerative and psychiatric diseases MESHD. KDM1A demethylates H3K4me1/2 and together with the histone deacetylases HDAC1/2, it forms part of co-repressor complexes recruited by zinc finger factors to control transcription. The exact role of KDM1A in neuroinflammation remained to be explored.  Methods Compounds were administered p.o. gavage to mice with MOG35-55 induced experimental autoimmune encephalomyelitis MESHD or mice infected with Theiler’s murine encephalomyelitis MESHD virus. Immune cell infiltration was analyzed by immunohistochemistry. Cytokine and chemokine levels were analyzed by ELISA. Genome wide gene expression in spinal cord and brain were analyzed by two-color microarray analysis and qRT-PCR. Results ORY-2001 improved the clinical score in mouse experimental autoimmune encephalomyelitis MESHD and in mice infected with the Theiler’s murine encephalomyelitis MESHD virus. The compound reduced lymphocyte egress and infiltration of immune cells in the spinal cord and prevented demyelination MESHD. ORY-2001 was more effective and/or faster acting than a sphingosine 1-phosphate receptor antagonist in the effector phase of the disease and reduced the induction of the inflammatory gene expression signature in the central nervous system more potently. Gene expression changes and axonal protection in animals, and protection against glutamate excitoxicity in spinal cord explants support that ORY-2001 has neuroprotective qualities.  Conclusions ORY-2001 exerts therapeutic activity in two mouse models of multiple sclerosis MESHD. The anti-inflammatory properties of ORY-2001 are being tested in a Phase IIa clinical trial in patients with relapse remitting and secondary progressive multiple sclerosis MESHD, and in severely ill COVID-19 MESHD patients at risk for acute respiratory distress syndrome MESHD

    Spectrum of spinal cord involvement in COVID-19 MESHD: A systematic review

    Authors: Ritwick Mondal; Shramana Deb; Gourav Shome; Upasana Ganguly; Durjoy Lahiri; Julian Benito Leon

    doi:10.1101/2020.09.29.20203554 Date: 2020-09-30 Source: medRxiv

    Background and aims- Recent reports reveal incidences of spinal cord involvement in form of para-infectious MESHD or post-infectious myelitis MESHD raising potential concerns about the possibilities of SARS-CoV-2 behind the pathogenesis of spinal cord demyelination MESHD. In this study, we intend to summarise so far available pieces of evidence documenting SARS-CoV-2 mediated spinal demyelination MESHD in terms of clinical, laboratory parameters and imaging characteristics. Methodology- This review was carried out based on the existing PRISMA (Preferred Report for Systemic Review and Meta-analyses) consensus statement. Data was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase and Cochrane library and Preprint servers up till 10th September, 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes "SARS-COV-2", " COVID-19 MESHD", " demyelination MESHD" etc. Results- A total of 21 cases were included from 21 case reports after screening from various databases and preprint servers. Biochemical analysis reveals that the majority of cases showed elevated CSF HGNC protein as well as lymphocytic pleocytosis MESHD. Interestingly, a majority of cases were found to be associated with long extensive transverse myelitis MESHD (LETM), and remaining cases were found to be associated with isolated patchy involvement or isolated short segment involvement or combined LETM and patchy involvement. Few cases were also found with significant co-involvement of the brain and spine based on the imaging data. Conclusion- It can be interpreted that SARS-CoV-2 may play a potential role in spinal demyelinating disorders MESHD in both para-infectious MESHD and post-infectious forms.

    Clinical, cerebrospinal fluid and neuroimaging findings in COVID-19 MESHD encephalopathy: a case series

    Authors: Raphael Tuma; Bruno Guedes; Rafael Carra; Bruno Iepsen; Julia Rodrigues; Antonio Edvan Camelo Filho; Gabriel Kubota; Maira Ferrari; Adalberto Studart-Neto; Mariana Oku; Sara Terrim; Cesar Lopes; Carlos Eduardo Passos Neto; Matheus Dalben; Julia De Souza; Jose Pedro Baima; Tomas Da Silva; Iago Perissinotti; Maria da Graca Martin; Marcia Goncalves; Ida Fortini; Jerusa Smid; Tarso Adoni; Leandro Lucatto; Ricardo Nitrini; Helio Gomes; Luiz Henrique Castro

    doi:10.1101/2020.08.28.20181883 Date: 2020-09-01 Source: medRxiv

    Objective - To describe the clinical, neurological, neuroimaging and cerebrospinal fluid ( CSF HGNC) findings associated with encephalopathy MESHD in patients admitted to a COVID-19 MESHD tertiary reference center. Methods - We retrospectively reviewed records of consecutive patients with COVID-19 MESHD evaluated by a consulting neurology team from March 30, 2020 through May 15, 2020. Results - Fifty-five patients with confirmed SARS-CoV-2 were included, 43 of whom showed encephalopathy MESHD, and were further divided into mild, moderate and severe encephalopathy MESHD groups. Nineteen patients (44%) had undergone mechanical ventilation and received intravenous sedatives. Eleven (26%) patients were on dialysis. Laboratory markers of COVID-19 MESHD severity were very common in encephalopathy MESHD patients, but did not correlate with the severity of encephalopathy MESHD. Thirty-nine patients underwent neuroimaging studies, which showed mostly non-specific changes. One patient showed lesions possibly related to CNS demyelination MESHD. Four had suffered an acute stroke MESHD. SARS-CoV-2 was detected by RT-PCR in only one of 21 CSF HGNC samples. Two CSF HGNC samples showed elevated white blood cell count and all were negative for oligoclonal bands. In our case series the severity of encephalopathy MESHD correlated with higher probability of death MESHD during hospitalization (OR = 5.5 for each increment in the degree of encephalopathy MESHD, from absent (0) to mild (1), moderate (2) or severe (3), p<0.001). Conclusion - In our consecutive series with 43 encephalopathy MESHD cases, neuroimaging and CSF HGNC analysis did not support the role of direct viral CNS invasion or CNS inflammation MESHD as the cause of encephalopathy MESHD.

    COVID-19 MESHD and Guillain-Barre Syndrome - a Case report

    Authors: Amira Sidig; Khabab Abbasher; Mutaz F. Digna; Mohamed Elsayed; Hussien Abbasher; Mohammed Abbasher; Abbasher Hussien

    doi:10.21203/rs.3.rs-48327/v1 Date: 2020-07-24 Source: ResearchSquare

    Coronaviruses are a family of related viruses that cause diseases in mammals and avians. Guillain-Barre syndrome MESHD is a rare disorder in which the body's immune system attacks peripheral nerves.The case:A 65 years old Sudanese male with no diabetes mellitus MESHD or hypertension MESHD present to the clinic; On examination, he has upper and lower limb weakness MESHD ( quadriplegia MESHD). The condition was preceded by upper respiratory tract infection MESHD. Chest X-ray showed features of pneumonia MESHD Chest CT scan showed multiple bilateral ground-glass opacities and consolidation typical of COVID-19 MESHD pneumonia MESHD. Brain MRI was normal. The COVID-19 MESHD nasal swab test was positive. Nerve conduction study showed evidence of polyradiculopathies MESHD with dominant demyelination MESHD supporting the diagnosis of Guillain-Barre syndrome MESHD. The patients died after seven days; because of progressive respiratory failure MESHD.

    Acute Demyelinating Encephalomyelitis (ADEM) in COVID-19 MESHD infection: A Case Series.

    Authors: Michaela McCuddy; Praful Kelkar; Yu Zhao; David Wicklund

    doi:10.1101/2020.07.15.20126730 Date: 2020-07-17 Source: medRxiv

    Objective: To report three patients infected with COVID-19 MESHD with severe respiratory syndrome MESHD requiring intubation, who developed acute demyelinating encephalomyelitis MESHD ( ADEM MESHD). Method: Patient data were obtained from medical records from the North Memorial Health Hospital, Robbinsdale, MN, USA Results: Three patients (two men and one woman, aged 38 - 63) presented with fatigue MESHD, cough MESHD and fever MESHD leading to development of acute respiratory distress syndrome MESHD secondary to COVID-19 MESHD infection requiring intubation and ventilatory support. Two patients were unresponsive, one with strong eye deviation to the left and the third patient had severe diffuse weakness MESHD. MRI in all patients showed findings consistent with ADEM MESHD. CSF showed elevated protein in all patients with normal cell count and no evidence of infection, including negative COVID-19 MESHD PCR. All three of the patients received Convalescent plasma therapy for COVID-19 MESHD. All patients were treated with intravenous corticosteroids and improved, although two responded minimally. Two patients treated with IVIG showed no further improvement. Conclusion: Neurological complications from COVID-19 MESHD are being rapidly recognized. Our three cases highlight the occurrence of ADEM MESHD as a postinfectious/immune mediated complication of COVID-19 MESHD infection, which may be responsive to corticosteroid treatment. Early recognition of this complication and treatment is important to avoid long term complications.

    Neurological manifestations associated with COVID-19 MESHD: a nationwide registry

    Authors: Elodie Meppiel; Nathan Peiffer-Smadja; Alexandra Maury; Imen Bekri; Cecile Delorme; Virginie Desestret; Lucas Gorza; Geoffroy Hautecloque-Raysz; Sophie Landre; Annie Lannuzel; Solene Moulin; Peggy Perrin; Paul Petitgas; Francois Sellal; Adrien Wang; Pierre Tattevin; Thomas de Broucker; - contributors to the NeuroCOVID registry

    doi:10.1101/2020.07.15.20154260 Date: 2020-07-16 Source: medRxiv

    Background: The clinical description of the neurological manifestations in COVID-19 MESHD patients is still underway. This study aims to provide an overview of the spectrum, characteristics and outcomes of neurological manifestations associated with SARS-CoV-2 infection MESHD. Methods: We conducted a nationwide, multicentric, retrospective study during the French COVID-19 MESHD epidemic in March-April 2020. All COVID-19 MESHD patients with de novo neurological manifestations were eligible. Results: We included 222 COVID-19 MESHD patients with neurological manifestations from 46 centers throughout the country. Median age was 65 years (IQR 53-72), and 136 patients (61.3%) were male. COVID-19 MESHD was severe or critical in almost half of the patients (102, 45.2%). The most common neurological diseases MESHD were COVID-19 MESHD associated encephalopathy MESHD (67/222, 30.2%), acute ischemic cerebrovascular syndrome MESHD (57/222, 25.7%), encephalitis MESHD (21/222, 9.5%), and Guillain-Barre Syndrome MESHD (15/222, 6.8%). Neurological manifestations appeared after first COVID-19 MESHD symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19 MESHD associated encephalopathy MESHD, 7 (5-10) days in encephalitis MESHD, 12 (7-18) days in acute ischemic cerebrovascular syndrome MESHD and 18 (15-28) days in Guillain-Barre Syndrome MESHD. Brain imaging was performed in 192 patients (86.5%), including 157 MRI (70.7%). Brain MRI of encephalitis MESHD patients showed heterogeneous acute non vascular lesion in 14/21 patients (66.7%) with associated small ischemic lesion or microhemorrhages MESHD in 4 patients. Among patients with acute ischemic cerebrovascular syndrome MESHD, 13/57 (22.8%) had multi territory ischemic strokes MESHD, with large vessel thrombosis MESHD in 16/57 (28.1%). Cerebrospinal fluid was analyzed in 97 patients (43.7%), with pleocytosis MESHD in 18 patients (18.6%). A SARS-CoV-2 PCR was performed in 75 patients and was positive only in 2 encephalitis MESHD patients. Among patients with encephalitis MESHD, ten out of 21 (47.6%) fully recovered, 3 of whom received corticosteroids (CS). Less common neurological manifestations included isolated seizure MESHD (8/222, 3.6%), critical illness neuropathy MESHD (8/222, 3.6%), transient alteration of consciousness (5/222, 2.3%), intracranial hemorrhage MESHD (5/222, 2.3%), acute benign lymphocytic meningitis MESHD (3/222, 1.4%), cranial neuropathy MESHD (3/222, 1.4%), single acute demyelinating lesion MESHD (2/222, 0.9%), Tapia syndrome MESHD (2/222, 0.9%), cerebral venous thrombosis MESHD (1/222, 0.5%), sudden paraparesis MESHD (1/222, 0.5%), generalized myoclonus MESHD and cerebellar ataxia MESHD (1/222, 0.5%), bilateral fibular palsy (1/222, 0.5%) and isolated neurological symptoms ( headache MESHD, anosmia MESHD, dizziness MESHD, sensitive or auditive symptoms MESHD, hiccups MESHD, 15/222, 6.8%). The median (IQR) follow-up of the 222 patients was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). Conclusion: Neurological manifestations associated with COVID-19 MESHD mainly included CAE, AICS, encephalitis MESHD and GBS MESHD. Clinical spectrum and outcomes were broad and heterogeneous, suggesting different underlying pathogenic processes.

    First Case Of SAR HGNC-Coronavirus-2 Sequencing In The Cerebrospinal Fluid Of A Patient With Suspected CNS Demyelinating Disease

    Authors: Renan Domingues; Maria Cássia Mendes-Correa; Fernando Brunale Vilela de Moura Leite; Ester Cerdeira Sabino; Ingra M Claro; Noely Evangelista Ferreira; Camila Malta Romano; Jaqueline Goes de Jesus; Daniel Wagner de Castro Lima Santos; Diego Zanotti Salarini; Carlos Senne

    doi:10.21203/rs.3.rs-31801/v1 Date: 2020-05-26 Source: ResearchSquare

    The association between coronaviruses and central nervous system (CNS) demyelinating lesions MESHD has been previously shown. However, no case has been described of an association between the novel coronavirus (SARS-COV-2) and CNS demyelinating disease MESHD so far. SARS-COV-2 was previously detected in cerebrospinal fluid (CSF) sample of a patient with encephalitis MESHD. However, the virus identity was not confirmed by deep sequencing of SARS-COV-2 detected in the CSF. Here, we report a case of a patient with mild respiratory symptoms MESHD and neurological manifestations compatible with Clinically Isolated Syndrome. The viral genome of SARS-COV-2 was detected and sequenced in CSF with 99.74 to 100% similarity between the patient virus and worldwide sequences. This report suggests a possible association of SARS COV-2 infection MESHD with neurological symptoms of demyelinating disease MESHD, even in the absence of relevant upper respiratory tract infection MESHD signs.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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