Document text
Principal Investigator: Lael Yonker
Organization: MASSACHUSETTS GENERAL HOSPITAL
Fiscal Year: 2024
Award: $828,233
Funding agency: National Heart Lung and Blood Institute
Over 15.6 million children in the U.S. alone have been infected by SARS-CoV2. While most recover, roughly 1
million children suffer from Long COVID. Neutrophils have been shown to be hyperactivated in Long COVID,
which is concerning because they can be quite inflammatory, causing vascular and tissue damage and
contributing to disease. We aim is to define the neutrophil profiles driving Long COVID in order to ultimately offer
novel strategies for diagnosing and treating this new disease. To achieve this goal, we will use both single-cell
RNA sequencing technology to define neutrophil activation profiles and microfluidics to test neutrophil
functionality Long COVID, compared to healthy controls. Our central hypothesis is that neutrophil activation in
Long COVID carries a distinct neutrophilic gene expression and functional profile, which contributes to
pathogenicity. Importantly, we aim to partner with an existing clinical trial of larazotide for Long COVID
(ClinicalTrials.gov Identifier: NCT05747534) to test reversibility of neutrophil activation by targeting sources of
Spike antigenemia. Ultimately, mechanisms driving the pathogenesis of this newly emerged post-COVID-19-
related illness must be defined to establish diagnostics and effective therapies.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><21+ years old><Acute><Adult><Adult Human><Affect><Antigen-Antibody Complex><Antigens><Assay><Automobile Driving><Bioassay><Biological Assay><Blood><Blood Neutrophil><Blood Plasma><Blood Platelets><Blood Polymorphonuclear Neutrophil><Blood Reticuloendothelial System><Blood Vessels><Body Tissues><Breathlessness><COVID infected patient><COVID patient><COVID positive patient><COVID-19 antigen><COVID-19 infected patient><COVID-19 infection><COVID-19 patient><COVID-19 positive patient><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 patient><COVID19 positive patient><COVID19 virus><Cell Body><Cells><Cessation of life><Chemotactic Cytokines><Chest Pain><Child><Child Youth><Childhood><Children (0-21)><Circulation><Clinical Treatment><Clinical Trials><Clotting><CoV-2><CoV2><Coagulation><Coagulation Process><Death><Diagnosis><Diagnostic><Disease><Disorder><Dyspnea><Employment><Esteroproteases><Expression Signature><Fatigue><Funding><Future><Gene Cluster><Gene Expression><Gene Expression Profile><Gene set enrichment analysis><Goals><Gut Epithelial Permeability><Gut Hyperpermeability><Gut permeability><Health><Health Care Costs><Health Costs><Healthcare Costs><Homologous Chemotactic Cytokines><IgA><Immune><Immune Complex><Immunes><Immunoglobulin A><In Vitro><Individual><Infection><Inflammation><Inflammatory><Inflammatory Response><Injury><Intercrines><Intervention><Intervention Strategies><Intestinal Epithelial Permeability><Intestinal Hyperpermeability><Intestinal permeability><Lack of Energy><Link><MIS-C><Marrow Neutrophil><Marrow platelet><Measures><Microfluidics><Mucosa><Mucosal Tissue><Mucous Membrane><Multiorgan Inflammatory Syndrome in Children><Multisystem Inflammatory Syndrome in Children><Neutrophil Activation><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Orthostatic tachycardia><Outcome><Pathogenesis><Pathogenicity><Pathway interactions><Peptidases><Peptide Hydrolases><Performance><Permeability><Phagocytosis><Phenotype><Plasma><Plasma Serum><Platelets><Play><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Population><Protease Gene><Proteases><Proteinases><Proteins><Proteolytic Enzymes><Proteomics><RNA Seq><RNA sequencing><RNAseq><Receptor Protein><Reporting><Reticuloendothelial System, Serum, Plasma><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 antigen><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><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><SIS cytokines><Sampling><Schools><Severe Acute Respiratory Coronavirus 2><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 coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Source><Stomach><Subgroup><Symptoms><Syndrome><Technology><Testing><Therapeutic><Thrombocytes><Tissues><Wuhan coronavirus><acute COVID-19><acute SARS-CoV-2 infection><acute phase of COVID-19><acute phase of SARS-CoV-2 infection><adulthood><antagonism><antagonist><chemoattractant cytokine><chemokine><coronavirus disease 2019 antigen><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus patient><driving><effective therapy><effective treatment><gastric><gastrointestinal><gene expression pattern><gene expression signature><hCoV19><immunogen><improved><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><injuries><interventional strategy><kids><migration><multisystem inflammatory syndrome of children><nCoV2><neutrophil><new approaches><novel approaches><novel strategies><novel strategy><pathway><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><pediatric><pediatric inflammatory multisystem syndrome><post-COVID><post-COVID-19><post-coronavirus disease 2019><programs><receptor><scRNA-seq><severe acute respiratory syndrome coronavirus 2 antigen><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single-cell RNA sequencing><social role><transcriptional profile><transcriptional signature><transcriptome sequencing><transcriptomic sequencing><trial regimen><trial treatment><vascular><youngster><zonulin><µfluidic>