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Principal Investigator: Joshua Kennedy
Organization: ARKANSAS CHILDREN'S HOSPITAL RES INST
Fiscal Year: 2024
Award: $694,403
Funding agency: National Heart Lung and Blood Institute
PROJECT SUMMARY
Respiratory viral coinfections (RVCIs) are more common in children than adults and have become increasingly
important due to the emergence of SARS-COV-2. However, the distinction between coinfection and codetection
remains unclear. Further, the association between finding multiple viruses using our current clinical methods and
the effect on clinical outcomes is nebulous. Understanding positive viral testing has become crucial with the
ongoing spread of SARS-CoV-2 and the treatment algorithms that are expensive or deleterious to patients with
other viruses. Currently, clinicians struggle to identify the dominant virus inducing the host immune response in
RVCIs in children. Our group has developed gene classifiers to identify adults with SARS-CoV-2 compared to
other viruses using nasopharyngeal swabs. Further, we are the first to develop a host/microbe classifier for
pediatric patients on the ventilator that will distinguish lower respiratory tract infections using lower airway
sampling. Here, our objective is to identify patient features, coinfecting viruses, microbial contributions, and host
responses that enhance disease severity in SARS-CoV-2–infected children. As the only pediatric hospital in the
state, Arkansas Children's Hospital is an ideal site for studying SARS-CoV-2 RVCIs. We aim to leverage our
unique multi-institutional collaborative team with extensive experience applying metagenomic next-generation
sequencing to simultaneously evaluate viral and host genetic material from clinically obtained nasopharyngeal
specimens. This approach identifies host–virus interactions and allows us to assess their impact on immune
responses and disease severity during RVCIs. We hypothesize that a combination of patient characteristics, viral
features, and host immune responses will predispose a child to more severe disease. We also expect to identify
an immunologic fingerprint for SARS-CoV-2 that can be used to identify it as the “infecting virus” in children with
codetections. The impact of this study is significant, and the multidisciplinary team that this proposal brings
together is experienced. By employing epidemiologic, -omic, and computational approaches, we will identify
immunologic fingerprints of SARS-CoV-2 infections in children, which can help identify the “infecting virus” when
multiple viruses are detected. Further, this study will provide distinction regarding the clinical implications of
codetections of viruses, including SARS-CoV-2, in children. The findings will support future clinical trials
evaluating treatment options based on the immunologic fingerprints that we identify.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><21+ years old><5 year old><5 years of age><Actemra><Acute respiratory infection><Adult><Adult Human><Affect><Age><Algorithms><Area Under Curve><Arkansas><COVID-19 infection><COVID-19 therapy><COVID-19 treatment><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><Characteristics><Child><Child Youth><Children (0-21)><Children's Hospital><Clinical><Clinical Treatment Moab><Clinical Trials><CoV-2><CoV2><Data><Disease><Disorder><Enterovirus><Epidemiology><Ethnic Origin><Ethnicity><Fingerprint><Functional Metagenomics><Future><Gender><Gene Expression><Genes><Genetic Materials><History><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune response><Immunochemical Immunologic><Immunodeficiency and Immunosuppression Disorders><Immunologic><Immunologic Diseases><Immunological><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Immunological response><Immunologically><Immunologics><Immunomodulators><Individual><Infection><Institution><Investigators><Knowledge><Laboratories><Lower Respiratory Tract Infection><Lower respiratory infection><Metagenomics><Methods><Microbe><Modeling><Monoclonal Antibodies><NGS Method><NGS system><Nasopharynx><Outcome><Pathogenicity><Patients><Pediatric Hospitals><Prevention><Prognosis><RSV infection><Race><Races><Recording of previous events><Research Personnel><Research Specimen><Researchers><Respiratory Syncytial Virus Infections><Respiratory syncytial virus><Rhinopharynx><Rhinovirus><Risk><SARS><SARS corona virus 2><SARS coronavirus disease><SARS-CO-V2><SARS-COVID-2><SARS-CoV disease><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 therapy><SARS-CoV-2 treatment><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><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><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><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome coronavirus disease><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><Severities><Severity of illness><Site><Specimen><Steroid Compound><Steroids><Symptoms><Testing><Vaccination><Ventilator><Viral><Viral Diseases><Virus><Virus Diseases><World Health Organization><Wuhan coronavirus><adulthood><age 5 years><ages><child health care provider><child healthcare provider><child patients><clinical material><co-infection><co-morbid><co-morbidity><coinfection><comorbidity><computer based prediction><coronavirus disease 2019 infection><coronavirus disease 2019 therapy><coronavirus disease 2019 treatment><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease-19 virus><disease severity><epidemiologic><epidemiological><experience><five year old><five years of age><hCoV19><histories><host response><immune modulators><immune system response><immunoresponse><improved><improved outcome><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><interest><kids><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><mAbs><microbe pathogen><microbial><microbial pathogen><monoclonal Abs><multidisciplinary><nCoV2><nasopharnygeal><nasopharyngeal swab><next gen sequencing><next generation sequencing><nextgen sequencing><novel><pathogenic microbe><pediatric care provider><pediatric health care provider><pediatric healthcare provider><pediatric patients><pediatric provider><pediatrician><predictive modeling><racial><racial background><racial origin><respiratory><respiratory pathogen><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 therapy><severe acute respiratory syndrome coronavirus 2 treatment><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><targeted drug therapy><targeted drug treatments><targeted drug trials><targeted pharmaceutical trials><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted therapy trials><targeted treatment><targeted treatment trials><tocilizumab><treat COVID-19><treat SARS-CoV-2><treat coronavirus disease 2019><treat severe acute respiratory syndrome coronavirus 2><viral detection><viral infection><viral testing><virus 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