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Principal Investigator: Michael A Portman
Organization: SEATTLE CHILDREN'S HOSPITAL
Fiscal Year: 2021
Award: $56,324
Funding agency: National Heart Lung and Blood Institute
PROJECT SUMMARY
Kawasaki Disease (KD) is systemic autoinflammatory vasculitis occurring in children and showing predilection
for attacking the coronary arteries. Despite 60 years of research, the etiology and pathogenesis for KD still
require elucidation. The predominant hypothesis regarding pathogenesis involves an unknown antigen,
possibly microbial, or super-antigen induced hyperimmune response occurring in genetically susceptible
individuals. Treatment includes inflammatory suppression with high dose immunoglobulin. However,
response, defined as persistent of fever, or continuing coronary vasculitis characterized by dilation and
aneurysm formation, is highly variable. The parent grant tests the hypothesis that treatment response depends
on pharmacogenetics, which is currently being probed with whole genome sequencing. Disease severity,
particularly formation of giant coronary aneurysms, could also depend on the pathogen signaling the immune
response. Currently, the world faces a pandemic from the novel human corona virus SARS-COV-2 resulting in
development of Covid-19 disease. This virus promotes a dramatic systemic inflammatory response, in some
ways mirroring that occurring in KD. Thus, prior studies have explored and suggested a role for corona virus
HCoV-NL63 in KD pathogenesis, although subject numbers displaying both KD and serological evidence for
corona have been limited due to relatively low infectivity of corona virus overall. In contrast, SARS-COV-2
shows high human to human transmission, and modeling shows that millions of Americans will eventually be
infected. This transmission alters the landscape for evaluating a potential role for corona viruses in
pathogenesis of KD in children. Covid-19 is particularly intriguing for KD as the SARS-COV-2 spike protein
binds to angiotensin converting enzyme2 (ACE2) as a receptor and promotes cellular entry of the virus. ACE2
enzymatically directs angiotensin2 to angiotensin (1-9), which promotes coronary arterial dilation, an important
aspect of KD. SARS-COV-2 infection severity in children currently appears to be mild leading to low rates of
testing (although we are now receiving reports of respiratory distress and even death in children and infants in
the U.S and throughout the world). Thus, the relationship of SARS-COV-2 and autoinflammatory pediatric
diseases such as KD remains unknown. This study will use existing grant infrastructure to determine
relationships between SARS-COV-2 infection and KD. We will also use this opportunity to determine antibody
response to SARS-COV-2 exposure in a febrile and afebrile Pediatric populations. The supplement scope will
be supported by UAB investigators, who are at the forefront of developing serological testing for SARS-COV-2,
as well as Seattle Children’s located at the initial U.S epicenter for the pandemic.
Terms: <0-11 years old><19S Gamma Globulin><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><7S Gamma Globulin><Ab-mediated immunity><Ab-mediated protection><American><Aneurysm><Angiitis><Angiotensins><Antibody Response><Antibody immunity><Antibody protection><Antibody-mediated protection><Antigens><Binding Proteins><Blood Serum><COVID-19><COVID-19 S protein><COVID-19 antibody><COVID-19 infection><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 testing><COVID-19 virus><COVID19><COVID19 S protein><COVID19 infection><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 testing><COVID19 virus><CV-19><CV19><Cardiac artery><Cardiac infarction><Causality><Cessation of life><Child><Child Youth><Childhood><Children (0-21)><CoV-2><CoV2><Control Groups><Coronary><Coronary Aneurysm><Coronary artery><Coronaviridae><Coronavirus><Data><Death><Development><Disease><Disorder><Dose><Etiology><Exhibits><Face><Fever><Genetic><Grant><HCoV><Heart artery><Human><IGIV><IV Immunoglobulins><IVIG><IgG><IgM><Immune Globulins><Immune globulin IV><Immune response><Immune signaling><Immunity><Immunochemical Immunologic><Immunoglobulin G><Immunoglobulin M><Immunoglobulins><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Individual><Infant><Inflammatory><Infrastructure><Institution><Intravenous Antibodies><Intravenous IG><Intravenous Immune Globulin><Intravenous Immunoglobulins><Investigators><Kawasaki Disease><Ligand Binding Protein><Ligand Binding Protein Gene><Modeling><Modern Man><Mucocutaneous Lymph Node Syndrome><Myocardial Infarct><Myocardial Infarction><Pathogenesis><Patients><Pattern><Pharmacogenetics><Population><Prediction of Response to Therapy><Protein Binding><Pyrexia><Reaction><Receptor Protein><Reporting><Research><Research Personnel><Researchers><Resistance><Respiratory distress><Role><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 antibody><SARS-CoV-2 exposure><SARS-CoV-2 infection><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 testing><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 antibody><SARS-CoV2 exposure><SARS-CoV2 infection><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-Related Coronavirus><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Serology><Serology test><Serum><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 Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><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 S protein><Severe acute respiratory syndrome coronavirus 2 exposure><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome related corona virus 2><Severities><Severity of illness><Symptoms><Testing><Time><Transmission><Vasculitis><Virus><Wuhan coronavirus><age dependent><age related><antibody against COVID-19><antibody against SARS-CoV-2><antibody against SARS-CoV2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody to COVID-19><antibody to SARS-CoV-2><antibody to SARS-CoV2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><antibody-mediated immunity><autoinflammatory><bound protein><cardiac infarct><causation><cohort><corona virus><corona virus disease 2019><coronary attack><coronary infarct><coronary infarction><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 antibody><coronavirus disease 2019 infection><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 testing><coronavirus disease 2019 virus><developmental><disease causation><disease severity><entire genome><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><faces><facial><febrile><febris><full genome><genome sequencing><hCoV19><heart attack><heart infarct><heart infarction><host response><human CoV><human corona virus><human coronavirus><immune system response><immunogen><immunoresponse><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><microbial><nCoV2><novel><pandemic><pandemic disease><parent grant><pathogen><pediatric><predict therapeutic response><predict therapy response><predict treatment response><receptor><resistance to therapy><resistant><resistant to therapy><response><response to treatment><serology assay><severe acute respiratory syndrome coronavirus 2 antibody><severe acute respiratory syndrome coronavirus 2 testing><severe acute respiratory syndrome-CoV><social role><systemic inflammation><systemic inflammatory response><therapeutic resistance><therapeutic response><therapy prediction><therapy resistant><transmission process><treatment prediction><treatment resistance><treatment response><treatment response prediction><vasculitides><whole genome><youngster>