Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Understanding of the fundamental processes underlying the versatile clinical manifestations of COVID-19 is incomplete without comprehension of how different immune cells are recruited to various compartments of virus-infected lungs, and how this recruitment differs among individuals with different levels of disease severity. As in other respiratory infections, leukocyte recruitment to the respiratory system in people with COVID-19 is orchestrated by specific leukocyte trafficking molecules, and when uncontrolled and excessive it results in various pathological complications, both in the lungs and in other organs. In the absence of experimental data from physiologically relevant animal models, our knowledge of the trafficking signals displayed by distinct vascular beds and epithelial cell layers in response to infection by SARS-CoV-2 is still incomplete. However, SARS-CoV-2 and influenza virus elicit partially conserved inflammatory responses in the different respiratory epithelial cells encountered early in infection and may trigger partially overlapping combinations of trafficking signals in nearby blood vessels. Here, we review the molecular signals orchestrating leukocyte trafficking to airway and lung compartments during primary pneumotropic influenza virus infections and discuss potential similarities to distinct courses of primary SARS-CoV-2 infections. We also discuss how an imbalance in vascular activation by leukocytes outside the airways and lungs may contribute to extrapulmonary inflammatory complications in subsets of patients with COVID-19. These multiple molecular pathways are potential targets for therapeutic interventions in patients with severe COVID-19.

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 是 2019 年冠状病毒病 (COVID-19) 的病原体。如果不了解不同的免疫细胞如何被募集到病毒感染的肺部的各个区室，以及这种募集在不同疾病严重程度的个体之间有何不同，那么对 COVID-19 多种临床表现背后的基本过程的理解是不完整的。与其他呼吸道感染一样，COVID-19 患者的白细胞招募到呼吸系统是由特定的白细胞运输分子精心策划的，当不受控制和过度时，会导致肺部和其他器官的各种病理并发症。由于缺乏生理相关动物模型的实验数据，我们对不同血管床和上皮细胞层响应 SARS-CoV-2 感染而显示的运输信号的了解仍然不完整。然而，SARS-CoV-2和流感病毒在感染早期遇到的不同呼吸道上皮细胞中引发部分保守的炎症反应，并可能触发附近血管中部分重叠的运输信号组合。在这里，我们回顾了原发性嗜肺流感病毒感染期间协调白细胞运输至气道和肺室的分子信号，并讨论了与原发性 SARS-CoV-2 感染不同过程的潜在相似之处。我们还讨论了气道和肺部外白细胞的血管激活失衡如何导致部分 COVID-19 患者出现肺外炎症并发症。 这些多分子途径是重症 COVID-19 患者治疗干预的潜在目标。