Human epidemiology and response to SARS-CoV-2 (HEROS)

  • Funded by National Institutes of Health (NIH)
  • Total publications:0 publications

Grant number: 3UM1AI114271-06S1

Grant search

Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2021
  • Known Financial Commitments (USD)

    $355,680
  • Funder

    National Institutes of Health (NIH)
  • Principle Investigator

    Pending
  • Research Location

    United States of America, Americas
  • Lead Research Institution

    UNIVERSITY OF WISCONSIN-MADISON
  • Research Category

    Epidemiological studies

  • Research Subcategory

    Disease transmission dynamics

  • Special Interest Tags

    Gender

  • Study Subject

    N/A

  • Clinical Trial Details

    N/A

  • Broad Policy Alignment

    Pending

  • Age Group

    Adults (18 and older)Children (1 year to 12 years)

  • Vulnerable Population

    Unspecified

  • Occupations of Interest

    Unspecified

Abstract

PI: Jackson, Daniel J., et. al. - Project Summary Admin. Supp NOT AI-20-031, PA-18-591 Supplement on Grant Number: 5UM1AI114271-06COVID-19 SURVEILLANCE STUDYSARS-CoV-2 causes severe respiratory disease seen predominantly in adults (COVID-19), but there is littleinformation regarding the infection burden in children. This is complicated by the observation that manyvirologically-confirmed cases in children are asymptomatic. Undocumented, and likely infectious, cases couldresult in exposure to a far greater proportion of the community than would otherwise occur. Indeed, it has beenproposed that undocumented (or silent) infections are the source for almost 80% of documented infections (Liet al, Science); thus, it is critical to determine the silent and symptomatic infection rate in children.To overcome challenges for clinical study implementation imposed by current healthcare access restrictions,we propose a surveillance study to determine the prevalence of SARS-CoV-2 infection (detection of virus innasal secretions) over time in children and their household contacts (caregivers and siblings). In addition to theneed for surveying children for asymptomatic SARS-CoV-2 infection, this study will allow a comparisonbetween children with asthma and other atopic conditions and children without those conditions.Figure 3.1 Study OverviewStudy designWe propose to conduct a prospective surveillance study in which children (index child) and their householdcontacts, including caregiver(s) and siblings, will be enrolled at study sites with NIH-funded studies. Potentialparticipants are those enrolled in existing NIH-funded studies (including the Wisconsin Infant Cohort Study, theChildhood Origins of Asthma [COAST] study, the MUPPITS-2 study, the RACR study and the UrbanEnvironment and Childhood Asthma[URECA] study). The intent is to recruit children who have asthma and/or other atopic conditions, as well ashealthy children, with extensive medical information and information on atopic status available as part of theirparticipation in cohort studies. The enrollment goal is approximately 2000 families to be enrolled overapproximately 2 weeks, and each participant will be observed for 6 months. During the study, biologicalsamples will be collected by the family at pre-determined intervals and symptom and exposure surveys will becompleted on-line at the time the biological samples are collected (Figure 1 Study Overview). Some biologicalsamples (nasal swabs and stool) will be collected by the caregiver at home. Blood samples will be collected ata home study visit or at an independent clinical laboratory, depending on feasibility. Samples will be processedin central laboratories, and Rho Inc. will serve as the coordinating center for the study.The primary outcome of the study will be the percent of index children and their household contacts withdetectable SARS-CoV-2 in nasal secretions. Secondary and exploratory outcomes are as described in thestudy protocol. PI: Jackson, Daniel J., et. al. - Project Summary Admin. Supp NOT AI-20-031, PA-18-591Supplement on Grant Number: 5UM1AI114271-06Project Summary (Primary award-ICAC)The overall goals of our proposal are designed to address current high priority unmetneeds in asthma that exist in inner cities, as well as elsewhere, including efforts to applyimmune-based strategies to reduce severity, diminish progression of disease, and teststrategies to prevent asthma. In that context, we hypothesize that environmental exposure toallergens, particularly cockroach, is a major risk factor for allergic sensitization and thedevelopment of asthma, and an important determinant of disease progression plus a target forimmunotherapy, severity and responsiveness to treatment. Moreover, we hypothesize thatIgE-sensitization, IgE-mediated processes, and wheezing with respiratory infections areimportant and linked risk factors in the development of asthma, and by targeting treatment toregulate IgE early in life it may be possible to prevent the progression from recurrent wheezingto asthma. Furthermore, asthma in inner-city children is represented by multiple phenotypes,some of which have uncontrolled disease which will benefit by treatment directed towardsphenotypic characteristics of their disease, e.g. exacerbation prone and obesity. Listed beloware our proposals to reach our goals and reduce unmet needs of asthma in the inner city.1. Aim 1. URECA, Urban Environment and Childhood Asthma is our inner-city birth cohort thatwas designed to establish the role and contribution of environmental risk factors on immunedevelopment and function that lead to asthma which will be further accomplished by studyingthe children until they are 14 to 16 years of age, and by this approach determine asthmaphenotypes and progression of disease.2. Aim 2. The Influence of the Inner City House Dust Microbiome and Respiratory andGastrointestinal Microbiome Composition Function and their Relationships to AllergicOutcomes. The overall aim of this mechanistic study is to determine whether the householdenvironment represents a significant source of bacteria that (1) populates respiratory and/orgastrointestinal microbiomes in early infancy; (2) to identify the key microbial species andfunction in both of these host niches that are associated with protection from asthma; (3) toidentify the microbial metabolic products and their function to shape immune responses; and (4)to pursue the development of protectivemicrobes as a treatment intervention to prevent asthma.3. Aim 3. Systems Biology Analysis in URECA. The overall aim of this mechanistic study is toextend the current ICAC2 epigenetic study to the application of a systems biology analysis tomore fully establish the complex integration of in utero and post-natal environmental stimuli,inherited factors, and dynamic biological responses in early childhood that predispose childrenin the inner city towards a Th2 phenotype and place them at risk for the development of asthma.4. Aim 4. The Immunobiology of Cockroach Sensitization - The Role of T Cells in Disease andImmunotherapy is a mechanistic study designed to test the hypothesis that different T-cellresponses to epitopes from aeroallergens, in this case cockroach, are important in thedevelopment of allergic airway disease and to determine their roles in immunomodulation byimmunotherapy. The proposed work will involve extensive collaboration with Aims 1 and 6.5. Aim 5. Preventing Progression to Asthma in Pre-School Aged Inner City Children (PAPI). Thisprotocol is aimed at the prevention of progression from recurrent wheezing to asthma and willaddress the hypothesis that treatment of high-risk inner-city children with allergic sensitizationand recurrent wheeze with omalizumab, an intervention directed towards IgE, will alter diseaseprogression as reflected by a reduced prevalence of asthma 2 years after the completion ofomalizumab therapy.6. Aim 6. Cockroach (CR) Immunotherapy (IT) in Inner-City Asthma: Effects on Disease Activityand Progression. The primary objective of this protocol is to determine whether the addition ofcockroach (CR) subcutaneous immunotherapy (IT) to standard, guideline-directed asthmamanagement is superior to standard asthma care alone in the treatment of persistent asthma in PI: Jackson, Daniel J., et. al. - Project Summary Admin. Supp NOT AI-20-031, PA-18-591 Supplement on Grant Number: 5UM1AI114271-06young inner-city children. Furthermore, by focusing on younger children, we will also test a keysecondary hypothesis as to whether the addition of CR IT will lead to a long-term reduction inasthma severity and persistence.7. Aim 7. Asthma Phenotype Informed Protocol (APIP). This protocol is designed to determine ifthe addition of mepolizumab, anti-IL-5, to treatment of children with difficult-to-control asthmaand peripheral blood eosinophilia (>300 cells/mm3) will prevent exacerbations, improve diseasecontrol, and potentially prevent progression of disease.8. Aim 8. The Use of Long-acting Anti-Muscarinic Antagonist (LAMA) Therapy in an Asthma andObesity Phenotype in Inner-City Asthma. This protocol is designed to test the hypothesis thatasthmatic children/adolescents with a BMI >85th percentile have enhanced parasympatheticairway tone, which is related to higher plasma leptin concentration and, as a consequence, willhave a greater response to anticholinergic treatment than asthma patients with lower BMIs.