Immune mediated lung injury in COVID-19

SARS-CoV-2及其引发的疾病(新冠肺炎)已成为全球主要公共卫生组织 在几个月的时间里对健康构成威胁。尤其是SARS-CoV-2，更是雪上加霜 急性呼吸道感染的数量，包括流感和细菌性肺炎，它们是 危及我们退伍军人和老龄化人口的健康。尤其是严酷的新冠肺炎 这种疾病的特征是严重的肺损伤，导致氧气严重受损。 分娩，最终导致多器官衰竭和死亡。我们正在进行的研究集中在 一组被称为中性粒细胞的白血球，它是最丰富的白血球 在我们的身体里，它被证明是一个关键的免疫细胞，对 肺损伤。然而，我们目前的医学知识不足以理解 中性粒细胞在病毒感染的背景下是这样做的。尽管中性粒细胞对消除 许多类型的感染，它们被认为是肺部发育的主要因素 伤害，以及如何平衡它们的有益活动和有害功能 明白了。因此，更好地了解中性粒细胞的行为和表型 在严重的SARS-CoV-2和其他病毒感染期间发生的改变将有助于开发新的 改善它们的抗菌功能，同时限制它们的有害影响的治疗。这个 我们在这项拨款中提出的研究将检验中性粒细胞如何有效地清除SARS-CoV-2 病毒，或者如果它们是被招募到肺部的过度激活的免疫细胞群 他们的有害活动超过了他们的好处。我们还将测试一种令人兴奋的新疗法 我们在加州大学洛杉矶分校的合作者开发的方法，看看这是否可以阻止 肺细胞上的中性粒细胞，同时阻止病毒复制。这个为期两年的项目的结果将是 提供对中性粒细胞的有益贡献和有害贡献的见解 严重新冠肺炎病的发展，并可能找到新的治疗方法使其受益 退伍军人和其他脆弱的病人。

SARS-CoV-2 and the disease it causes (COVID-19) has emerged as a major global public health threat in the span of a few months. In particular, SARS-CoV-2 adds to the present number of acute respiratory infections, including influenza and bacterial pneumonia, which are endangering the health of our veterans and aging population. In particular, severe COVID-19 disease is characterized by severe lung injury, which results in severely impaired oxygen delivery and ultimately multiple organ failure and death. Our ongoing research has focused on a population of white blood cells called neutrophils, which are the most abundant white blood cell in our body and which have been shown to be a pivotal immune cell that contributes greatly to lung injury. However, our current medical knowledge is inadequate for understanding what neutrophils do in the context of viral infection. Although neutrophils are critical for eliminating many types of infections, they are believed to be a major contributor to the development of lung injury, and how to balance their beneficial activities with their harmful functions is poorly understood. Therefore, a better understanding of how neutrophils behavior and phenotype are altered during severe SARS-CoV-2 and other viral infections would aid in developing novel therapies to improve their antimicrobial functions, while limiting their injurious effects. The research we propose in this grant will examine how well neutrophils eliminate SARS-CoV-2 viruses, or if they are an excessively activated population of immune cells recruited to the lung whose harmful activities outweighs their benefits. We also will test an exciting new treatment approach developed by our collaborator at UCLA to see if this can block the damaging effects of neutrophils on lung cells, while blocking viral replication. The results of this 2-year project will provide insights into the beneficial versus harmful contributions of neutrophils in the development of severe COVID-19 disease, and potentially identify new therapies to benefit veterans and other vulnerable patients.