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SARS-CoV-2 and Influenza Infection in the Syrian Hamster

叙利亚仓鼠的 SARS-CoV-2 和流感感染

基本信息

批准号：
10175735
负责人：
Caroline J Zeiss
金额：
$ 45.05万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10175735
关键词：
2019-nCoV Acute American Animal Model Binding Biological Markers Blood Body Weight Bronchoalveolar Lavage COVID-19 Cells Clinical Clinical Course of Disease Complement Data Disease Electron Microscopy Environmental Health Face Future Goals Hamsters Histopathology Human Immune Immune response Immunologics Infection Influenza Influenza A Virus, H1N1 Subtype Influenza A virus Injury Innate Immune Response Interferon-alpha Interferon-beta Interferons Kinetics Lung Lung diseases Mesocricetus auratus Modeling Morbidity - disease rate Mus Outcome Measure Population Prevention Risk Factors Safety Seasons Serum Severities Social Distance Spleen Structure of respiratory epithelium Therapeutic Studies Tissues United States Vaccines Viral Viral Load result Viral Respiratory Tract Infection Virus Diseases Work acute infection biosafety level 3 facility clinical phenotype clinically relevant cytokine design enteric infection falls influenzavirus light microscopy pathogen receptor respiratory response sex synergism vaccine trial

项目摘要

PROJECT SUMMARY In a few months, a potential second wave of CoVID-19 will be superimposed on the influenza season, which starts in the fall and typically peaks between December and February in the United States. By then, the majority of Americans are unlikely to be immune to SARS-CoV-2. An effective SARS-CoV-2 vaccine is likely to take months to years to achieve widespread protection. In addition, reduced social distancing is likely to elicit regional surges in CoVID-19. Potential synergy between these two respiratory pathogens could result in significant morbidity in the short-term. In the long term, we face the reality that SARS-CoV-2 may assume endemic status and may interact with other seasonal respiratory pathogens for the foreseeable future. The overall goal of this proposal is to determine whether prior influenza infection worsens CoVID-19- like disease in the SARS-CoV-2 Syrian hamster model. Recent studies indicate that ACE2 may be upregulated by influenza infection. The Syrian hamster supports infection with human influenza A H1N1 subtypes as well as contemporary H3N2 subtypes that cannot replicate in mice. Additionally, the Syrian hamster is a faithful spontaneous animal model of CoVID-19. We will pursue two aims: 1) to characterize interferon-driven immune responses and ACE2 expression in hamsters infected intranasally with contemporary H3N2 and H1N1 influenza strains and 2) to characterize clinical disease course, immune responses and translationally relevant biomarker alterations following SARS-CoV-2 infection of acutely infected and recovered influenza-infected hamsters. We will use a factorial design to assess the effects of controllable variables (influenza virus infection alone, combined influenza/ SARS-CoV-2, acute/recovered status and sex) on clinically relevant outcome measures (body weight, duration/severity of clinical illness and pulmonary injury scoring). Cytokine, immune and ACE2 responses will allow us to assess association of these variables with infection status and clinical phenotype. These approaches will provide direct and translationally relevant data regarding impact of influenza on SARS-CoV-2 clinical phenotype, as well as advance understanding of underlying immune responses.

项目摘要几个月后，潜在的第二波COVID-19将叠加在流感季节，从秋季开始，通常在12月和12月之间达到高峰。 2月，美国。到那时，大多数美国人不太可能对SARS-CoV-2免疫。一种有效的SARS-CoV-2疫苗可能需要几个月的时间，多年来，实现了广泛的保护。此外，减少社交距离可能会引发了新冠肺炎疫情的区域性激增。这两种呼吸系统之间的潜在协同作用病原体可能在短期内导致严重的发病率。从长远来看，我们面临 SARS-CoV-2可能成为地方病并可能与其他病毒相互作用，季节性呼吸道病原体。这个项目的总体目标是建议是确定先前的流感感染是否与COVID-19相似 SARS-CoV-2叙利亚仓鼠模型中的疾病。最近的研究表明，ACE 2 可能会被流感感染上调。叙利亚仓鼠支持感染人类甲型流感H1N1亚型以及当代H3 N2亚型，在小鼠中复制。此外，叙利亚仓鼠是一种忠实的自发动物模型 COVID-19我们将追求两个目标：1）表征干扰素驱动的免疫鼻内感染当代抗结核药物的仓鼠中的反应和ACE 2表达 H3 N2和H1N1流感病毒株和2）表征临床病程，免疫 SARS-CoV-2后的应答和预防相关生物标志物改变急性感染和恢复的流感感染仓鼠的感染。我们将使用一个析因设计，以评估可控变量（流感病毒感染）的影响单独、合并流感/ SARS-CoV-2、急性/恢复状态和性别）相关结局指标（体重、临床疾病的持续时间/严重程度和肺损伤评分）。细胞因子、免疫和ACE 2反应将使我们能够评估这些变量与感染状态和临床表型的相关性。这些这些方法将提供关于以下方面影响的直接和相关的数据：流感对SARS-CoV-2临床表型影响，以及对潜在的免疫反应。