Dissecting the drivers of persistent SARS-CoV-2 infections
剖析 SARS-CoV-2 持续感染的驱动因素
基本信息
- 批准号:10736007
- 负责人:
- 金额:$ 83.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-17 至 2028-06-30
- 项目状态:未结题
- 来源:
- 关键词:2019-nCoV3-DimensionalAccelerationAccountingAddressAgeAntibodiesAntiviral AgentsAreaB-LymphocytesBackBioinformaticsBiologicalBiological AssayBiological ModelsBloodCOVID-19COVID-19 detectionCOVID-19 pandemicCOVID-19 patientCase StudyCharacteristicsChronicClinicalClinical TreatmentCollaborationsCommunicable DiseasesComputerized Medical RecordDataData SetDimensionsEnvironmentEpitheliumEvolutionFlow CytometryFrequenciesFundingGenderGeneral PopulationGenetic Complementation TestGenetic RecombinationGenomicsGenotypeGrantHaplotypesHealth systemHospitalsHumanImmuneImmune EvasionImmune responseImmunocompromised HostImmunologicsImmunologyIndividualInfectionInterferonsKnowledgeLinkMalignant NeoplasmsMapsMedical RecordsMetadataMinorityMolecularMolecular VirologyMutationNew York CityPathogenicityPathologyPatientsPeer ReviewPhenotypePhysiciansPopulationPositioning AttributePredispositionProcessProne PositionPropertyProteinsPublicationsRNARecoveryResearchResearch PersonnelResistanceResolutionResourcesRisk FactorsRoleSARS-CoV-2 infectionSARS-CoV-2 variantSamplingScientistSerumSurveillance ProgramT-LymphocyteTestingTherapeuticTherapeutic InterventionTranslational ResearchVaccinationVariantViralVirusWorkacute infectionantagonistbetacoronaviruschronic infectioncohortdemographicselectronic datafitnessglobal healthinsightmetropolitanmultidisciplinarynasopharyngeal swabnovelpandemic diseasepathogenpatient subsetspressurepreventpublic health emergencyrisk mitigationsurveillance datatransmission processvariants of concernviral genomicsvirology
项目摘要
The coronavirus disease 2019 (COVID-19) pandemic caused by the betacoronavirus “severe acute respiratory
syndrome coronavirus 2” (SARS-CoV-2) represents an unprecedented public health emergency. Most patients
with COVID-19 clear the virus upon resolution of the acute infection but ongoing, persistent, SARS-CoV-2
replication has been documented in immunocompromised individuals. In these chronically infected patients,
recovery of replication-competent virus over several weeks to months is linked to stepwise acquisition of
mutations within and outside of spike. Our preliminary data show that such prolonged intra-host viral evolution
plays a role in the emergence of new, antigenically distinct, SARS-CoV-2 variants. We propose to systematically
elucidate the determinants of persistent SARS-CoV-2 infections using an integrated translational research
approach combining real-world clinical metadata with bioinformatics, genomics and molecular virology. We will
leverage an existing large surveillance dataset covering two and a half years of SARS-CoV-2 spread in New
York City going back to the beginning of the pandemic in the spring of 2020 when the NY metropolitan area
emerged as one of the early epicenters of the pandemic. Specific Aim 1 will dissect the clinical features and
therapeutic interventions associated with persistent SARS-CoV-2 replication using existing longitudinal data from
electronic medical records. These studies will be complemented by the analysis of the B and T cell populations
of persistently infected patients. Specific Aim 2 will dissect the viral genotypes representative of intra-host
evolution of prolonged periods with a special emphasis on co-circulating viral variants. Specific Aim 3 will
examine the phenotypic properties of persistent SARS-CoV-2 variants with an emphasis on convergent evolution
within and outside of the spike region (susceptibility to neutralization, fusogenicity, spike processing and
interferon antagonism).
Altogether, the proposed studies address a critical knowledge gap regarding the biological drivers and viral
dynamics fueling the selection of SARS-CoV-2 viral variants during persistent SARS-CoV-2 infection. This
knowledge will provide the scientific basis needed to treat and prevent such chronic infections thereby limiting
the emergence and spread of increasingly neutralization-resistant yet transmissible SARS-CoV-2 variants.
由β冠状病毒“严重急性呼吸道感染”引起的2019年冠状病毒病(COVID-19)大流行
冠状病毒2型综合征(SARS-CoV-2)是一种前所未有的公共卫生紧急情况。大多数患者
COVID-19在急性感染消退后清除病毒,但持续、持续、SARS-CoV-2
在免疫功能低下的个体中已经记录了复制。在这些慢性感染患者中,
在几周到几个月内恢复有复制能力的病毒与逐步获得
刺突内外的突变我们的初步数据表明,这种长时间的宿主内病毒进化
在新的、抗原性不同的SARS-CoV-2变体的出现中起作用。我们建议系统地
使用综合转化研究阐明SARS-CoV-2持续感染的决定因素
方法结合现实世界的临床元数据与生物信息学,基因组学和分子病毒学。我们将
利用现有的大型监测数据集,涵盖两年半的SARS-CoV-2传播,
约克市回到2020年春季大流行开始时,纽约大都会地区
成为大流行病的早期中心之一。具体目标1将剖析临床特征,
使用现有的纵向数据与SARS-CoV-2持续复制相关的治疗干预
电子病历。这些研究将通过分析B和T细胞群来补充
持续感染的病人。具体目标2将剖析代表宿主内
长期的演变,特别强调共循环病毒变异。第3章将
研究持续性SARS-CoV-2变异体的表型特性,重点是趋同进化
尖峰区域内部和外部(对中和、融合性、尖峰处理和
干扰素拮抗作用)。
总而言之,拟议的研究解决了关于生物驱动因素和病毒的关键知识差距
在持续的SARS-CoV-2感染期间,动力学促进了SARS-CoV-2病毒变异体的选择。这
知识将提供治疗和预防这种慢性感染所需的科学基础,
越来越多的耐中和但可传播的SARS-CoV-2变种的出现和传播。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Viviana A Simon', 18)}}的其他基金
Understanding antibody responses and defining correlates of protection for endemic and pandemic coronavirus strains
了解抗体反应并定义地方性和大流行性冠状病毒株保护的相关性
- 批准号:
10549479 - 财政年份:2023
- 资助金额:
$ 83.13万 - 项目类别:
Preventing CD4+ T memory cells from becoming HIV reservoirs
防止 CD4 T 记忆细胞成为 HIV 储存库
- 批准号:
9914204 - 财政年份:2018
- 资助金额:
$ 83.13万 - 项目类别:
Targeting HIV persistence in CD4+ T memory stem cells
靶向 CD4 T 记忆干细胞中的 HIV 持久性
- 批准号:
9321252 - 财政年份:2016
- 资助金额:
$ 83.13万 - 项目类别:
HTLV-1 antagonists of HIV restriction factors
HIV限制因子的HTLV-1拮抗剂
- 批准号:
8651884 - 财政年份:2013
- 资助金额:
$ 83.13万 - 项目类别:
HTLV-1 antagonists of HIV restriction factors
HIV限制因子的HTLV-1拮抗剂
- 批准号:
8466151 - 财政年份:2013
- 资助金额:
$ 83.13万 - 项目类别:
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