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Principal Investigator: SAMUEL JEREMY PLEASURE
Organization: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Fiscal Year: 2021
Award: $323,000
Funding agency: National Institute of Neurological Disorders and Stroke
PROJECT ABSTRACT
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 autoimmunity triggered by SARS-CoV-2
infection. 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 — particularly those caused by para-
infectious autoimmunity. 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 could immediately impact clinical management.
Over the past 7 years, a unique interdisciplinary team of neurologists and basic scientists at UCSF was
formed to develop and deploy an integrated approach to rapidly 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 >1,500
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. We seek emergency funding to accelerate our work on identifying anti-
neural autoantibodies associated with SARS-CoV-2 infection in patients with neurologic syndromes in 1
immediate aim.
Aim 1: Identify autoantibodies in the CSF of COVID-19 patients with neurologic syndromes.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><7S Gamma Globulin><AIDP><Active Follow-up><Acute><Acute Autoimmune Neuropathy><Acute Infective Polyneuritis><Acute Inflammatory Demyelinating Polyradiculoneuropathy><Acute Inflammatory Polyneuropathy><Acute Inflammatory Polyradiculoneuropathy><Antibodies><Antigens><Antiviral Agents><Antiviral Drugs><Antivirals><Apoplexy><Assay><Autoantibodies><Autoantigens><Autoimmune><Autoimmune Status><Autoimmunity><Autologous Antigens><Bioassay><Biologic Assays><Biological Assay><Biological Markers><Body Tissues><Brain><Brain Hypoxia-Ischemia><Brain Inflammation><Brain Nervous System><Brain Vascular Accident><CNS Nervous System><COVID infected patient><COVID patient><COVID positive patient><COVID-19><COVID-19 infected patient><COVID-19 infection><COVID-19 patient><COVID-19 positive patient><COVID-19 screening><COVID-19 virus><COVID19><COVID19 infection><COVID19 patient><COVID19 positive patient><COVID19 screening><COVID19 virus><CV-19><CV19><Cell Body><Cells><Central Nervous System><Cerebral Stroke><Cerebrospinal Fluid><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Child><Child Youth><Children (0-21)><Children's Hospital><Chronic><Clinical><Clinical Management><Clinical Research><Clinical Study><CoV emergence><CoV-2><CoV2><Collaborations><Collection><Complex><Custom><Data><Decision Making><Detection><Development><Disease><Disorder><Emergencies><Emergency Situation><Encephalitis><Encephalon><Encephalopathies><Enrollment><Functional Metagenomics><Funding><General Hospitals><Guillain Barré Syndrome><Guillaine-Barre Syndrome><Health><Human><Human Resources><Hypercoagulability><IgG><Immune><Immune Precipitation><Immunes><Immunofluorescence><Immunofluorescence Immunologic><Immunoglobulin G><Immunoprecipitation><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Incubated><Infection><Inflammation><Inflammatory><Infrastructure><Investigators><Kidney Failure><Kidney Insufficiency><Laboratories><Landry's paralysis><Landry-Guillain-Barre Syndrome><Libraries><Maintenance><Manpower><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Mediating><Medical center><Metagenomics><Mice><Mice Mammals><Modern Man><Moods><Murine><Mus><NGS Method><NGS system><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><Neuraxis><Neurologic><Neurological><Neurologist><Neuropathogenesis><Out-patients><Outpatients><Pathogenesis><Patients><Pediatric Hospitals><Peripheral><Personality><PhIP-seq><Phage Display><Phage ImmunoPrecipitation Sequencing><Phenotype><Process><Proteome><Protocol><Protocols documentation><Pure Seminoma><Renal Failure><Renal Insufficiency><Research><Research Personnel><Researchers><SARS corona virus 2><SARS-CoV-2><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 screening><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><San Francisco><Scientist><Self-Antigens><Seminoma><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Staining method><Stains><Steroid Compound><Steroids><Stroke><Syndrome><Systemic disease><Testing><Therapeutic><Thrombophilia><Time><Tissues><Transfection><United States National Institutes of Health><Universities><Viral><Work><Wuhan coronavirus><active followup><acute flaccid myelitis><acute idiopathic polyneuritis><acute post-infectious polyneuropathy><acute postinfectious polyneuropathy><anti-viral agents><anti-viral drugs><anti-virals><autoimmune antibody><autoreactive antibody><base><bio-markers><biologic marker><biomarker><brain attack><cerebral spinal fluid><cerebral vascular accident><cerebrovascular accident><clinical phenotype><clinically actionable><cohort><corona virus disease 2019><corona virus emergence><coronavirus disease 2019><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 screening><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus emergence><coronavirus patient><developmental><emergent CoV><emergent corona virus><emergent coronavirus><emerging CoV><emerging corona virus><emerging coronavirus><enroll><experiment><experimental research><experimental study><follow up><follow-up><followed up><followup><hCoV19><hypoxia ischemia><immune suppression><immunogen><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><innovate><innovation><innovative><insight><men><men's><nCoV><nCoV2><neural><neural mechanism><neuroinflammation><neuroinflammatory><neuromechanism><new CoV><new corona virus><new coronavirus><next gen sequencing><next generation sequencing><nextgen sequencing><novel><novel CoV><novel corona virus><novel coronavirus><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><personnel><pleasure><programs><prospective><relating to nervous system><self reactive antibody><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><severe acute respiratory syndrome coronavirus 2 screening><spinal fluid><youngster>