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

项目总结 再过几个月，潜在的第二波新冠肺炎将叠加在 流感季节，从秋季开始，通常在12月和12月之间达到高峰 美国的二月。到那时，大多数美国人不太可能是 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来 几年才能实现广泛的保护。此外，减少社交距离可能会 引发了新冠肺炎的地区性热潮。这两种呼吸道之间的潜在协同作用 病原体可能会在短期内导致显著的发病率。从长远来看，我们面临着 SARS-CoV-2可能呈现流行状态并可能与其他病毒相互作用的现实 在可预见的未来，季节性呼吸道病原体。这个项目的总体目标是 建议确定之前感染过流感是否会恶化类似新冠肺炎 SARS-CoV-2叙利亚仓鼠模型中的疾病。最近的研究表明，ACE2 可能会因流感感染而上调。叙利亚仓鼠支持感染 人类甲型H1N1流感亚型以及当代H3N1亚型 在小鼠身上复制。此外，叙利亚仓鼠是忠实的自发动物模型 新冠肺炎。我们将追求两个目标：1)表征干扰素驱动的免疫 金黄地鼠鼻内感染当代病毒后的反应和血管紧张素转换酶2的表达 H3N1和H1N1流感病毒株；2)确定临床病程，免疫 SARS-CoV-2后的应答和翻译相关生物标志物的变化 感染急性感染和康复的流感感染仓鼠。我们将使用 用于评估可控变量(流感病毒感染)效果的析因设计 单独、合并流感/SARS-CoV-2、急性/康复状态和性别)在临床上 相关结果衡量标准(体重、临床病程/严重程度和 肺损伤评分)。细胞因子、免疫和ACE2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关系。这些 方法将提供关于以下影响的直接和翻译相关数据 流感对SARS-CoV-2临床表型的影响以及对 潜在的免疫反应。

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.