It is currently believed that innate immunity is unable to prevent the spread of SARS-CoV-2 from the upper airways to the alveoli of high-risk groups of patients. SARS-CoV-2 replication in ACE-2-expressing pneumocytes can drive the diffuse alveolar injury through the cytokine storm and immunothrombosis by upregulating the transcription of chemokine/cytokines, unlike several other respiratory viruses. Here we report histopathology data obtained in post-mortem lung biopsies of COVID-19, showing the increased density of perivascular and septal mast cells (MCs) and IL-4-expressing cells (n = 6), in contrast to the numbers found in pandemic H1N1-induced pneumonia (n = 10) or Control specimens (n = 10). Noteworthy, COVID-19 lung biopsies showed a higher density of CD117⁺ cells, suggesting that c-kit positive MCs progenitors were recruited earlier to the alveolar septa. These findings suggest that MC proliferation/differentiation in the alveolar septa might be harnessed by the shift toward IL-4 expression in the inflamed alveolar septa. Future studies may clarify whether the fibrin-dependent generation of the hyaline membrane, processes that require the diffusion of procoagulative plasma factors into the alveolar lumen and the endothelial dysfunction, are preceded by MC-driven formation of interstitial edema in the alveolar septa.

目前认为，先天免疫无法阻止SARS-CoV-2从高危人群患者的上呼吸道传播至肺泡。与其他几种呼吸道病毒不同，表达 ACE-2 的肺细胞中的 SARS-CoV-2 复制可以通过细胞因子风暴和免疫血栓形成，通过上调趋化因子/细胞因子的转录来驱动弥漫性肺泡损伤。在此，我们报告了在 COVID-19 死后肺活检中获得的组织病理学数据，显示血管周围和间隔肥大细胞 (MC) 以及表达 IL-4 的细胞 (n = 6) 的密度增加，与大流行性 H1N1 诱发的肺炎 (n = 10) 或对照标本 (n = 10)。值得注意的是，COVID-19 肺活检显示 CD117 ⁺细胞密度较高，表明 c-kit 阳性 MC 祖细胞较早被招募到肺泡间隔。这些发现表明，肺泡间隔中的 MC 增殖/分化可能是通过发炎的肺泡间隔中向 IL-4 表达的转变来利用的。未来的研究可能会阐明透明膜的纤维蛋白依赖性生成（需要促凝血浆因子扩散到肺泡腔和内皮功能障碍的过程）是否先于 MC 驱动的肺泡间隔间质水肿形成。