Immune mediated lung injury in COVID-19

SARS-CoV-2及其引起的疾病（COVID-19）已成为全球公众关注的主要问题， 几个月内的健康威胁。特别是SARS-CoV-2给现在增加了 急性呼吸道感染，包括流感和细菌性肺炎， 危及退伍军人和老龄化人口的健康。特别是，严重的COVID-19 这种疾病的特征是严重的肺损伤，这导致严重的氧气受损 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个 一群称为中性粒细胞的白色血细胞，是最丰富的白色血细胞 在我们的身体，已被证明是一个关键的免疫细胞，大大有助于 肺损伤然而，我们目前的医学知识不足以理解 嗜中性粒细胞在病毒感染的情况下是这样的。虽然中性粒细胞对于消除 许多类型的感染，他们被认为是一个主要贡献者的发展，肺 伤害，以及如何平衡其有益的活动与有害的功能是很差的 明白因此，更好地了解中性粒细胞的行为和表型是如何 在严重的SARS-CoV-2和其他病毒感染期间改变将有助于开发新的 治疗，以提高其抗微生物功能，同时限制其有害作用。的 我们在这项拨款中提出的研究将检查中性粒细胞如何消除SARS-CoV-2 病毒，或者如果它们是过度激活的免疫细胞群， 他们的行为弊大于利我们还将测试一种令人兴奋的新疗法 我们的合作者在加州大学洛杉矶分校开发的方法，看看这是否可以阻止破坏性的影响， 肺细胞上的中性粒细胞，同时阻断病毒复制。这个为期两年的项目将 提供了对中性粒细胞的有益和有害贡献的见解， 发展严重的COVID-19疾病，并可能发现新的治疗方法， 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.