Human rhinovirus infection and susceptibility to SARS-CoV-2 infection and symptomatic disease

人类鼻病毒感染以及对 SARS-CoV-2 感染和症状性疾病的易感性

• 批准号: 10726391
• 负责人: CARLOS G GRIJALVA
• 金额: $ 27.01万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-20 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10726391
• 关键词: 2019-nCoV; Adult; Age; Animal Model; Attenuated; COVID-19; COVID-19 pandemic; COVID-19 susceptibility; Cells; Cessation of life; Child; Circulation; Clinical; Development; Disease; Experimental Models; Frequencies; Health; Hospitalization; Household; Human; Immunologics; In Vitro; Individual; Infection; Inflammatory; Influenza; Interferons; Kinetics; Longitudinal cohort; Measures; Mediating; Nose; Pathogenesis; Pattern; Phase; Predisposition; Prevention strategy; Recording of previous events; Reporting; Respiratory Tract Infections; Respiratory syncytial virus; Rhinovirus; Rhinovirus infection; Risk; Risk Reduction; Role; SARS-CoV-2 infection; SARS-CoV-2 inhibitor; SARS-CoV-2 transmission; Sampling; Secondary to; Seminal; Severity of illness; Study models; Subgroup; Symptoms; Testing; Vaccination; Viral; Viral Interference; Virus; Virus Shedding; Work; case-based; chronic infection; clinically relevant; co-infection; experience; experimental study; indexing; individual variation; innovation; insight; member; pandemic disease; prevent; reduce symptoms; respiratory; respiratory virus; response; sample collection; severe COVID-19; sociodemographic factors; transmission process

ABSTRACT Children tend to experience more frequent asymptomatic infections and milder illnesses associated with SARS-CoV-2 infections than adults, but the reasons for these age-associated differences are unclear. While typical patterns of respiratory syncytial virus, influenza, and other viruses were markedly disrupted during the early pandemic, human rhinoviruses (HRVs) remained prevalent. Unlike other respiratory viruses, HRVs, consisting of species A, B, and C, are detected frequently year-round, and HRV infection is often asymptomatic, especially in children, who frequently undergo frequent re-infections with new HRV strains. The immunological consequences of these frequent HRV reinfections are unclear. Studies have suggested a role for HRV infection in rendering individuals less susceptible to infection with heterologous respiratory viruses, including SARS-CoV-2, with recent studies reporting that infection with HRV may trigger interferon responses that block SARS-CoV-2 replication and reduce SARS-CoV-2 transmission. While insightful, many prior observations of HRV interference with SARS-CoV-2 or other viruses are derived from ecological studies or animal models of infection, in which the experimental conditions are closely controlled. Observations from individuals in real-world conditions with detailed information on the sequence of infections, specimen collection prior to development of symptoms, and clinical features of illness are scarce. We aim to overcome these limitations by leveraging an intensive case-based longitudinal SARS-CoV-2 household surveillance platform, with daily nasal sampling and symptom assessment for 14 days following a positive test of the index SARS-CoV-2 case, to test the innovative hypothesis that interactions between HRV and SARS-CoV-2 may reduce the risk of symptomatic SARS-CoV-2 infection, reduce clinical symptoms among symptomatic infected individuals, and reduce transmission of SARS-CoV-2 in humans. We further hypothesize that these interactions may be HRV species-specific. We propose to build upon supportive experimental and in vitro studies to evaluate the clinical relevance of HRV and SARS-CoV-2 interactions in real-world settings by studying two Specific Aims: 1) To test the hypothesis that prevalent HRV infections reduce susceptibility to SARS-CoV-2 infection among exposed household members, and 2) To test the hypothesis that prevalent HRV infection reduces the risk of symptomatic infection or reduces symptom intensity upon SARS-CoV-2 infection. By assessing the impact of HRV co-infection on the individual variability observed in SARS-CoV-2 susceptibility to infection and disease severity, findings from the proposed study may yield new insights into ARI pathogenesis and development of enhanced prevention strategies.

摘要 儿童往往会经历更频繁的无症状感染和相关的轻度疾病 SARS-CoV-2感染者比成年人多，但这些年龄相关差异的原因尚不清楚。 虽然呼吸道合胞病毒、流感病毒和其他病毒的典型模式被明显破坏， 在早期大流行期间，人鼻病毒（HRV）仍然流行。与其他呼吸道病毒不同， 由A、B和C种组成的HRV全年都经常被检测到，并且HRV感染通常是 无症状，特别是在儿童中，他们经常经历新的HRV毒株的频繁再次感染。的 这些频繁的HRV再感染的免疫学后果尚不清楚。研究表明， 对于HRV感染使个体不易感染异源呼吸道病毒， 包括SARS-CoV-2，最近的研究报告称，HRV感染可能引发干扰素反应 阻断SARS-CoV-2复制并减少SARS-CoV-2传播。 虽然有见地，但许多先前关于HRV干扰SARS-CoV-2或其他病毒的观察结果是错误的。 来源于生态学研究或感染的动物模型，其中实验条件接近 控制。在真实世界条件下对个体的观察， 感染、症状出现前的标本收集和疾病的临床特征都很少。 我们的目标是通过利用密集的基于病例的纵向SARS-CoV-2 家庭监测平台，每天进行鼻腔采样和症状评估，持续14天， SARS-CoV-2病例的阳性检验，以检验HRV之间相互作用的创新假设 和SARS-CoV-2可能降低症状性SARS-CoV-2感染的风险， 有症状的感染者，并减少SARS-CoV-2在人类中的传播。我们进一步假设 这些相互作用可能是HRV物种特异性的。我们建议建立在支持性实验和 体外研究，以评估HRV和SARS-CoV-2相互作用在现实世界中的临床相关性， 本研究有两个具体目的：1）验证流行性HRV感染降低易感性的假设 暴露家庭成员中SARS-CoV-2感染，和2）为了检验假设， 普遍的HRV感染降低了症状性感染的风险或降低了症状强度， SARS-CoV-2感染。通过评估HRV合并感染对个体变异性的影响， SARS-CoV-2对感染和疾病严重程度的易感性，拟议研究的结果可能会产生新的 深入了解ARI发病机制和制定加强预防战略。