Early airway responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are of interest since they could decide whether coronavirus disease-19 (COVID-19) will proceed to life-threatening pulmonary disease stages. Here I discuss endothelial-epithelial co-operative in vivo responses producing first-line, humoral innate defence opportunities in human airways. The pseudostratified epithelium of human nasal and tracheobronchial airways are prime sites of exposure and infection by SARS-CoV-2. Just beneath the epithelium runs a profuse systemic microcirculation. Its post-capillary venules respond conspicuously to mucosal challenges with autacoids, allergens and microbes, and to mere loss of epithelium. By active venular endothelial gap formation, followed by transient yielding of epithelial junctions, non-sieved plasma macromolecules move from the microcirculation to the mucosal surface. Hence, plasma-derived protein cascade systems and antimicrobial peptides would have opportunity to operate jointly on an unperturbed mucosal lining. Similarly, a plasma-derived, dynamic gel protects sites of epithelial sloughing-regeneration. Precision for this indiscriminate humoral molecular response lies in restricted location and well-regulated duration of plasma exudation. Importantly, the endothelial responsiveness of the airway microcirculation differs distinctly from the relatively non-responsive, low-pressure pulmonary microcirculation that non-specifically, almost irreversibly, leaks plasma in life-threatening COVID-19. Observations in humans of infections with rhinovirus, coronavirus 229E, and influenza A and B support a general but individually variable early occurrence of plasma exudation in human infected nasal and tracheobronchial airways. Investigations are warranted to elucidate roles of host- and drug-induced airway plasma exudation in restriction of viral infection and, specifically, whether it contributes to variable disease responses following exposure to SARS-CoV-2.

中文翻译：

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早期体液防御：有助于将 COVID-19 限制在导气管中？

对严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 感染的早期气道反应很有趣，因为它们可以决定冠状病毒病 19 (COVID-19) 是否会进入危及生命的肺部疾病阶段。在这里，我讨论了在人体气道中产生一线、体液先天防御机会的内皮-上皮协同体内反应。人鼻和气管支气管的假复层上皮是 SARS-CoV-2 暴露和感染的主要部位。就在上皮细胞的下方，有大量的全身微循环。它的毛细血管后小静脉对粘膜自体物质、过敏原和微生物的挑战以及仅仅对上皮细胞的损失有显着的反应。通过活跃的小静脉内皮间隙形成，随后上皮连接的短暂屈服，未筛分的血浆大分子从微循环移动到黏膜表面。因此，血浆衍生的蛋白质级联系统和抗菌肽将有机会在未受干扰的粘膜内层上共同发挥作用。同样，血浆衍生的动态凝胶可以保护上皮脱落再生的部位。这种不分青红皂白的体液分子反应的精确性在于血浆渗出的位置有限和调节良好的持续时间。重要的是，气道微循环的内皮反应明显不同于相对无反应的低压肺微循环，后者在危及生命的 COVID-19 中非特异性、几乎不可逆地泄漏血浆。观察人类感染鼻病毒、冠状病毒 229E、甲型和乙型流感支持在人类感染的鼻腔和气管支气管气道中普遍但个体可变的早期血浆渗出发生。有必要进行调查以阐明宿主和药物诱导的气道血浆渗出在限制病毒感染中的作用，特别是它是否有助于在暴露于 SARS-CoV-2 后引起不同的疾病反应。