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Principal Investigator: MICHAEL A LYNES
Organization: CONNECTICUT CHILDREN'S MEDICAL CENTER
Fiscal Year: 2022
Award: $195,200
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
PROJECT SUMMARY / ABSTRACT – No Changes From the Original Application
In adults, SARS-CoV-2 infection exhibits a wide range of clinical outcomes, from asymptomatic and mild disease
to severe viral pneumonia, respiratory distress, acute kidney injury, thrombotic disorders, and serious cardiac,
cerebrovascular and vascular complications. Severe infection can also occur both in children and young adults
(< 21), and a significant proportion of children admitted with Covid-19 require ICU support, frequently including
mechanical ventilation. In addition, children and adolescents with initially asymptomatic SARS-CoV-2 infection
have presented with a rare, but very severe multisystem inflammatory syndrome (MIS-C). Epidemiologic, clinical
and laboratory predictors of progression towards severe forms of acute infection with SARS-CoV-2 and MIS-C
are thus urgently needed in the fight against Covid-19 in this population. As defined in the NIH Rapid
Acceleration of Diagnostics (RADx) program, biomarker discovery can enable risk stratification and guide
interventional studies to target Covid-19 patients at enhanced risk of developing complications and/or severe
disease. To target this discovery initiative, herein we will use a battery of biological, immunological and molecular
tests, including Grating-Coupled Fluorescence Plasmonic (GCFP) and advanced flow cytometry, to study
children and young adults (<21 years) with mild, moderate or severe SARS-CoV-2 infection. GCFP allows the
use of disposable biosensor chips that can be mass-produced at low cost and spotted in microarray format to
greatly increase multiplexing capabilities. In addition, we will use a similar biomarker approach for rapid
differentiation of patients with MIS-C versus other pediatric infectious or inflammatory conditions where the
clinical presentation resembles MIS-C, most importantly Kawasaki disease. A child's biologic and immunologic
response to SARS-CoV-2 exposure is likely influenced by a variety of factors, including genetics, epigenetics
and products of the mucosa/gut-brain axis, adipose tissue and neuroendocrine immune network, and further
modulated by environmental exposures. With these factors in mind, we hypothesize that a child's biomarker
profile in response to SARS-CoV-2 infection enables a timely and accurate prediction of severity of Covid-19
and diagnosis of MIS-C, and will help guide treatment strategies, and predict patient outcomes. To test this
hypothesis, we will use a non-traditional diagnostic and comprehensive biomarker discovery to characterize the
clinical and laboratory spectrum of children and adolescents with mild, moderate and severe SARS-CoV-2
infection, as well as MIS-C. We will then validate our newly developed diagnostic and prognostic algorithm to
distinguish MIS-C from other inflammatory disorders with overlapping clinical manifestations, including Kawasaki
disease, and predict the longitudinal risk of complications.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><21+ years old><7S Gamma Globulin><ARDS><Acute><Acute Renal Failure with Renal Papillary Necrosis><Acute Respiratory Distress><Acute Respiratory Distress Syndrome><Adipose tissue><Adolescent><Adolescent Youth><Adult><Adult ARDS><Adult Human><Adult RDS><Adult Respiratory Distress Syndrome><Antibodies><Antibody Affinity><Antibody Repertoire><Antibody Response><Antigenic Determinants><Assay><Asthma><Attention><Binding Determinants><Bioassay><Biologic Assays><Biologic Products><Biological><Biological Agent><Biological Assay><Biological Markers><Biological Products><Biosensor><Blood Vessels><Bronchial Asthma><COVID disease severity><COVID infected patient><COVID patient><COVID positive patient><COVID severity><COVID-19><COVID-19 S protein><COVID-19 antibody><COVID-19 diagnosis><COVID-19 disease severity><COVID-19 exposure><COVID-19 genome><COVID-19 infected patient><COVID-19 infection><COVID-19 patient><COVID-19 positive patient><COVID-19 severity><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus genome><COVID19><COVID19 S protein><COVID19 diagnosis><COVID19 disease severity><COVID19 genome><COVID19 infection><COVID19 patient><COVID19 positive patient><COVID19 severity><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 virus><COVID19 virus genome><CV-19><CV19><Cardiac><Child><Child Youth><Childhood><Children (0-21)><Clinical><CoV emergence><CoV-2><CoV2><Collaborations><Colombia><Coupled><Da Nang Lung><Development><Diagnostic><Disease><Disorder><Drugs><Elderly><Enrollment><Environmental Exposure><Epidemiology><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Epitopes><Exhibits><Fatty Tissue><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Fluorescence><GI microbiome><Generalized Growth><Generations><Genetic><Grant><Growth><Gut Mucosa><Humoral Immunities><IgG><Immune><Immune response><Immunes><Immunochemical Immunologic><Immunoglobulin G><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Infection><Inflammatory><Inflammatory Bowel Diseases><Inflammatory Bowel Disorder><Intervention Studies><Kawasaki Disease><Kinetics><Laboratories><Libraries><MIS-C><Measures><Mechanical ventilation><Medication><Mind><Molecular><Molecular Configuration><Molecular Conformation><Molecular Stereochemistry><Mucocutaneous Lymph Node Syndrome><Multiorgan Inflammatory Syndrome in Children><Multisystem Inflammatory Syndrome in Children><NIH><National Institutes of Health><Neuroendocrine><Neuroendocrine System><Neurosecretory Systems><Nucleocapsid><Obesity><Oral><Outcome><Parents><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Phage Display><Pharmaceutic Preparations><Pharmaceutical Preparations><Population><Proteins><RADx><RNA immunization><RNA vaccination><RNA vaccine><RNA-based vaccine><Rapid Acceleration of Diagnostics><Respiratory distress><Risk><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 antibody><SARS-CoV-2 diagnosis><SARS-CoV-2 disease severity><SARS-CoV-2 exposure><SARS-CoV-2 genome><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 severity><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 antibody><SARS-CoV2 exposure><SARS-CoV2 genome><SARS-CoV2 infection><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><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 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><Shock Lung><Stiff lung><Surface Plasmon Resonance><Symptoms><Syndrome><Technology><Testing><Thrombosis><Time><Tissue Growth><United States><United States National Institutes of Health><Vaccinated><Vaccination><Vaccines><Variant><Variation><Viral Pneumonia><Virus><Wuhan coronavirus><accurate diagnosis><acute infection><acute kidney injury><adipose><adiposity><adolescent minority><adult youth><adulthood><advanced age><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after severe acute respiratory distress syndrome CoV-2 infection><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-based immunity><antigen antibody affinity><bio-markers><biologic><biologic marker><biological 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respiratory syndrome coronavirus 2 antibody><severe acute respiratory syndrome coronavirus 2 diagnosis><severe acute respiratory syndrome coronavirus 2 disease severity><severe acute respiratory syndrome coronavirus 2 genome><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 severity><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><stratify risk><thrombotic disease><thrombotic disorder><treatment strategy><vascular><wet lung><white adipose tissue><yellow adipose tissue><young adult><young adulthood><young 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