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Mechanisms of Gastrointestinal COVID-19

Mechanisms of Gastrointestinal COVID-19
胃肠道 COVID-19 的机制
批准号:
10538795
负责人:
MATTHEW AARON CIORBA
金额:
$30.4万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-03-10 至 2022-07-14
关键词:
16S ribosomal RNA sequencing2019-nCoVACE2Abdominal PainAcuteAddressAdrenal Cortex HormonesAffectAutomobile DrivingCOVID-19COVID-19 patientCOVID-19 severityCOVID-19 vaccinationCathepsin LCathepsinsCathepsins BCell DeathCellsChronicClinicalColitisConfusionCoronavirusCrohn&aposs diseaseDataDiarrheaDiseaseEnteralEnterocytesEnvironmental Risk FactorEpithelialEpithelial CellsEtiologyFecesFoundationsFunctional disorderFutureGastrointestinal DiseasesGastrointestinal PhysiologyGastrointestinal tract structureGenotypeHealthHomeostasisHouseholdHumanImmuneImmune responseImpairmentInfectionInflammationInflammatory Bowel DiseasesIntegration Host FactorsInternationalIntestinal ContentIntestinal DiseasesIntestinesInvestigationK-18 conjugateKnowledgeLate EffectsLeadLiquid substanceLiteratureLower Gastrointestinal TractMesalamineModelingMolecularMucosal Immune ResponsesMucosal ImmunityMucositisMusNausea and VomitingObservational StudyOrganoidsOutcomePathogenesisPathogenicityPathologyPathway interactionsPatientsPharmaceutical PreparationsPhenotypePopulations at RiskRecommendationReporterReportingRespiratory SystemSARS-CoV-2 P.1SARS-CoV-2 infectionSamplingSeverity of illnessSignal TransductionSmall IntestinesSouth AfricanSpecimenStandardizationSymptomsTNF geneTestingTherapeuticTherapeutic immunosuppressionTransgenic MiceTropismViral Load resultViral reservoirVirusVirus ReplicationVulnerable Populationsacute infectionbasebile saltsbiobankclinical careclinical practicedifferential expressiondisease diagnosisenteric infectionexperiencegastrointestinalgastrointestinal symptomgut dysbiosisgut inflammationgut microbiomehost-microbe interactionsinfection rateinhibitorintestinal epitheliummicrobiomemicrobiome therapeuticsmicrobiotamortalitynovelnovel coronavirusrespiratorysocioeconomicsstool samplesurveillance studytoolvirologyviromevirus resource

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英文摘要
Project Summary Although coronavirus disease 2019 (COVID-19) is primarily defined as a respiratory illness, patients often experience clinical gastrointestinal symptoms, including abdominal pain and diarrhea. We recently found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, infects and replicates in human small bowel intestinal epithelial cells (IECs). However, the molecular mechanisms of SARS- CoV-2 driving gastrointestinal pathology, particularly in vulnerable populations with preexisting diseases remain unclear. In this proposal, our overall objectives are to better define the cellular signaling of SARS-CoV-2 interactions with IECs, enteric immune responses, and microbiome in the context of health or inflammatory bowel disease (IBD). Our preliminary data suggest that compared to normal COVID-19 patients, those with IBD have higher expression of cathepsin L in IECs, which correlated with higher viral loads. Our central hypothesis is that SARS- CoV-2 induces a distinctive intestinal pathology and mucosal immune response that is shaped by host factors (IBD), luminal factors (secretions, bile salts, and microbiome), and therapeutics (mesalamine). Specifically, using healthy and IBD-derived organoids, COVID-19 patient fecal samples, and K18-hACE2 mice, we aim to (1) define the host factors and cellular mechanisms involved in SARS-CoV-2 infection of normal and IBD epithelium, (2) determine the impact of intestinal SARS-CoV-2 infection on intestinal immune response and colitis, and (3) define the environmental factors that influence intestinal infection with SARS-CoV-2. With extensive and collaborative expertise in IBD, virology, and host-microbial interactions, we expect to address mechanistically interesting and clinically important questions like “What is the intestinal pathogenicity of SARS-CoV-2 and how is it impacted by IBD?”, “What is the interaction of SARS-CoV-2/COVID-19 with intestinal inflammation and IBD therapies?”, and “What is the impact of intestinal contents and IBD diagnosis/microbiome on intestinal SARS-CoV-2?”. We anticipate that this pathology will further our understanding of SARS-CoV-2 interactions with the epithelial and immune cells to explain COVID-19 GI symptoms with or without IBD. We also expect the new information gained from this project will expand our understanding of acute gastrointestinal pathology and symptoms of COVID-19, provide mechanistic context to existing clinical and translational literature, and create a foundational knowledge and tool set for deeper investigations into COVID-19 and potentially pathogenic and emerging coronaviruses of the future.
期刊论文(1)
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DOI: 10.1128/mbio.01308-22
发表时间: 2022-08-30
期刊: mBio
影响因子: 6.4
作者: []
通讯作者:
Targeting Tryptophan Metabolism in Rectal Cancer
  • 批准号:
    10754178
  • 项目类别:
  • 资助金额:
    $51.38万
  • 财政年份:
    2023
  • 负责人:
    MATTHEW AARON CIORBA
  • 依托单位:
Mechanisms of Gastrointestinal COVID-19
  • 批准号:
    10467855
  • 项目类别:
  • 资助金额:
    $58.4万
  • 财政年份:
    2022
  • 负责人:
    MATTHEW AARON CIORBA
  • 依托单位:
Mechanisms of Gastrointestinal COVID-19
  • 批准号:
    10665643
  • 项目类别:
  • 资助金额:
    $70.58万
  • 财政年份:
    2022
  • 负责人:
    MATTHEW AARON CIORBA
  • 依托单位:
TARGETING TRYPTOPHAN METABOLISM IN COLITIS ASSOCIATED CANCER
  • 批准号:
    9270026
  • 项目类别:
  • 资助金额:
    $34.31万
  • 财政年份:
    2016
  • 负责人:
    MATTHEW AARON CIORBA
  • 依托单位:
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微米和纳米塑料作用下2019-nCoV抗病毒药物利巴韦林对河蚬的毒性作用机制
  • 批准号:
  • 项目类别:
    省市级项目
  • 资助金额:
    10.0万元
  • 批准年份:
    2021
  • 负责人:
    郭晓宇
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  • 批准号:
    82030002
  • 项目类别:
    专项基金项目
  • 资助金额:
    135万元
  • 批准年份:
    2020
  • 负责人:
    曹彬
  • 依托单位:
基于人口流动大数据的新型冠状病毒(2019-nCoV)输出感染风险及接触网络传播模型研究
云南驯养野生动物中新型冠状病毒(2019-nCoV)溯源调查与验证
  • 批准号:
    --
  • 项目类别:
    --
  • 资助金额:
    140万元
  • 批准年份:
    2020
  • 负责人:
    夏雪山
  • 依托单位: