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.

抽象的 儿童往往会更频繁地经历无症状感染和相关的较轻疾病 SARS-CoV-2 感染率高于成人，但这些与年龄相关的差异的原因尚不清楚。 虽然呼吸道合胞病毒、流感和其他病毒的典型模式被明显破坏 在大流行早期，人类鼻病毒（HRV）仍然普遍存在。与其他呼吸道病毒不同， HRV 由 A、B、C 种组成，全年频繁检出，HRV 感染常发生在 无症状，尤其是儿童，他们经常频繁地再次感染新的 HRV 毒株。这 这些频繁的 HRV 再次感染的免疫学后果尚不清楚。研究表明有一个作用 HRV 感染使个体不易受异源呼吸道病毒感染， 包括 SARS-CoV-2，最近的研究报告称，HRV 感染可能会引发干扰素反应 阻止 SARS-CoV-2 复制并减少 SARS-CoV-2 传播。 虽然 HRV 干扰 SARS-CoV-2 或其他病毒的许多先前观察结果颇有见地，但 来自生态研究或感染动物模型，其中实验条件密切相关 受控。个人在现实世界条件下的观察，包含有关序列的详细信息 感染、出现症状前的标本收集以及疾病的临床特征很少。 我们的目标是通过利用基于病例的密集纵向 SARS-CoV-2 克服这些限制 家庭监测平台，在感染后 14 天内每天进行鼻腔采样和症状评估 对 SARS-CoV-2 病例进行阳性检测，以检验 HRV 之间相互作用的创新假设 SARS-CoV-2 可能会降低有症状的 SARS-CoV-2 感染风险，减轻临床症状 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。我们建议以支持性实验和实践为基础 体外研究评估 HRV 和 SARS-CoV-2 相互作用在现实环境中的临床相关性 研究两个具体目标：1) 检验流行的 HRV 感染降低易感性的假设 暴露的家庭成员中的 SARS-CoV-2 感染，以及 2) 检验以下假设： 流行的 HRV 感染可降低症状感染的风险或减轻症状强度 SARS-CoV-2 感染。通过评估 HRV 合并感染对观察到的个体差异的影响 SARS-CoV-2 对感染的易感性和疾病严重程度，拟议研究的结果可能会产生新的结果 深入了解 ARI 发病机制并制定强化预防策略。