Humoral Immune Mechanisms of Acute and Chronic Neurologic Sequelae of COVID-19
COVID-19急慢性神经系统后遗症的体液免疫机制
基本信息
- 批准号:10573297
- 负责人:
- 金额:$ 62.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-15 至 2025-11-30
- 项目状态:未结题
- 来源:
- 关键词:2019-nCoVAcuteAdultAnatomyAnimal Disease ModelsAnimal ModelAntibodiesAntibody RepertoireAntigensAntiviral AgentsAutoantibodiesAutoantigensAutoimmuneAutoimmune encephalitisAutoimmunityB-LymphocytesBehavioral AssayBiological AssayBiological MarkersBloodBrainCOVID-19COVID-19 complicationsCOVID-19 patientCell SeparationCellsCentral Nervous SystemCerebrospinal FluidChildChronicClinicalClinical ManagementClinical ResearchClonal ExpansionCollaborationsComplexCoronavirusCross ReactionsDataDetectionDevelopmentDiseaseEncephalitisEncephalopathiesEnrollmentEpitope MappingFunctional disorderGeneral HospitalsGenerationsGoalsGuillain Barré SyndromeHospitalizationHumanHumoral ImmunitiesImmuneImmune responseImmunofluorescence ImmunologicImmunoprecipitationImmunosuppressionImmunotherapyInfectionInflammationInflammatoryInfrastructureInfusion proceduresLaboratoriesLaboratory FindingMaintenanceMapsMass Spectrum AnalysisMedical centerMetagenomicsMolecularMolecular MimicryMonoclonal AntibodiesMoodsMultiple SclerosisMusNeuroanatomyNeurologicNeurologistNeuropathogenesisNucleic AcidsOutpatientsPathogenesisPathogenicityPatientsPediatric HospitalsPeripheral Nervous SystemPersonalityPhage DisplayPhage ImmunoPrecipitation SequencingPhenotypePlasma CellsPlayProductionProteomeProtocols documentationRNAResolutionRodentRoleSARS-CoV-2 antibodySARS-CoV-2 infectionSARS-CoV-2 spike proteinSamplingSan FranciscoScientistSeminomaSensitivity and SpecificityStainsSteroidsSyndromeTestingTissuesUnited States National Institutes of HealthUniversitiesViralViral AntibodiesVirus DiseasesWorkacute flaccid myelitisadaptive immune responseanimal model developmentbiobankbiomarker identificationbrain tissueclinical careclinical centerclinical phenotypeclinically actionablecohortcross reactivityexperimental studyextracellularhuman coronavirusin vivoinnovationinsightmenmicrobialmonoclonal antibody productionneuralneuroinflammationneurologic sequelae of COVID-19neuromechanismnext generation sequencingnovelnovel coronavirusoverexpressionpathogenic autoantibodiespleasurepost-COVID-19prospectivescreeningtreatment strategyviral detection
项目摘要
PROJECT SUMMARY
COVID-19 is associated with a growing number of peripheral and central nervous system complications.
It has become clear that a subset of these syndromes, including acute necrotizing encephalopathy, steroid-
responsive encephalitis and Guillain-Barré syndrome, are likely due to direct viral neuroinvasion and/or
autoimmunity triggered by SARS-CoV-2. There is an urgent need to prospectively investigate the acute and
chronic neurologic complications of COVID-19 and determine which syndromes are neuroinflammatory in origin.
While anti-viral therapeutics are still being developed for SARS-CoV-2, autoimmune CNS conditions can be very
responsive to immunosuppression. Thus, identifying biomarkers for a subset of COVID-19 patients with
autoimmune CNS syndromes in particular could immediately impact clinical management.
Over the past 8 years, a unique interdisciplinary team of neurologists and basic scientists at UCSF was
formed to develop and deploy an integrated approach to rapidly identify microbial nucleic acid, anti-viral
antibodies and anti-neural antibodies associated with encephalitis, with the explicit intent to discover and
validate clinically actionable biomarkers in addition to uncovering the fundamental mechanisms of disease
pathogenesis underlying these syndromes. The centerpiece of these efforts is an ongoing patient cohort called
the NID (Neuroinflammatory Disease) cohort, consisting of patients with suspected infectious or inflammatory
encephalitis. This cohort is now >1,400 patients referred by clinicians at UCSF and from other centers around
the world. Already, this cohort has spurred the development of the first ever clinically validated cerebrospinal
fluid metagenomic next-generation sequencing assay, the identification of a novel paraneoplastic autoimmune
syndrome with important implications for men with seminoma and the identification of enteroviral CSF
antibodies in children with acute flaccid myelitis. Here, we propose to adapt this existing clinical research
and laboratory infrastructure to enroll and investigate the urgent question whether COVID-19 patients
with ongoing neurologic sequelae have CNS inflammation. We will perform this work in collaboration
with colleagues at the NIH, Yale University as well as at UCSF Medical Center, Zuckerberg San
Francisco General Hospital and UCSF Benioff Children’s Hospital. Using our unique clinical and molecular
approach, we will investigate this hypothesis through the following specific aims:
Aim 1: Characterize autoantibodies in the CSF of COVID-19 patients with acute and chronic neurologic
syndromes
Aim 2: Identify CSF specific antibody repertoires in COVID-19 patients with neurologic complications using
high-resolution SARS-CoV-2 proteome-wide antibody profiling
Aim 3: Elucidate autoantibody pathogenicity through production of monoclonal antibodies from clonally
expanded CSF B cells in COVID-19 patients to enable the development of animal models of disease
项目总结
项目成果
期刊论文数量(0)
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{{ truncateString('SAMUEL JEREMY PLEASURE', 18)}}的其他基金
Humoral Immune Mechanisms of Acute and Chronic Neurologic Sequelae of COVID-19
COVID-19急慢性神经系统后遗症的体液免疫机制
- 批准号:
10387637 - 财政年份:2022
- 资助金额:
$ 62.95万 - 项目类别:
Elucidating the interaction between SHH and FGF signaling pathway in postnatal neurogenesis
阐明 SHH 和 FGF 信号通路在产后神经发生中的相互作用
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10405888 - 财政年份:2021
- 资助金额:
$ 62.95万 - 项目类别:
NMDA receptors and callosal circuitry: development and molecular mechanisms
NMDA 受体和胼胝体回路:发育和分子机制
- 批准号:
9896570 - 财政年份:2020
- 资助金额:
$ 62.95万 - 项目类别:
NMDA receptors and callosal circuitry: development and molecular mechanisms
NMDA 受体和胼胝体回路:发育和分子机制
- 批准号:
10612860 - 财政年份:2020
- 资助金额:
$ 62.95万 - 项目类别:
NMDA receptors and callosal circuitry: development and molecular mechanisms
NMDA 受体和胼胝体回路:发育和分子机制
- 批准号:
10393520 - 财政年份:2020
- 资助金额:
$ 62.95万 - 项目类别:
Exploiting the hair-brain connection to treat perinatal brain disease
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8412155 - 财政年份:2011
- 资助金额:
$ 62.95万 - 项目类别:
Exploiting the hair-brain connection to treat perinatal brain disease
利用头发与大脑的联系来治疗围产期脑部疾病
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8173388 - 财政年份:2011
- 资助金额:
$ 62.95万 - 项目类别:
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