Rationale: ACE2 (angiotensin-converting enzyme 2), the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is expressed in type 2 alveolar epithelial cells (AT2) that may play key roles in postinjury repair. An imbalance between ACE2 and ACE has also been hypothesized to contribute to lung injury. Objectives: To characterize the expression and distribution of ACE2 and ACE and to compare AT2 with endothelial cell expression in coronavirus disease (COVID-19)-related or -unrelated acute respiratory distress syndrome (ARDS) and controls. Methods: Lung tissue stainings (using multiplex immunofluorescence) and serum concentrations of ACEs were determined retrospectively in two different cohorts of patients. AT2 and endothelial cells were stained in lung tissue for ProSPC (pro-surfactant protein C) and CD31, respectively. Measurements and Main Results: Pulmonary ACE2 expression was increased in patients with COVID-19-related and -unrelated ARDS (0.06% of tissue area and 0.12% vs. 0.006% for control subjects; P = 0.013 and P < 0.0001, respectively). ACE2 was upregulated in endothelial cells (0.32% and 0.53% vs. 0.01%; P = 0.009 and P < 0.0001) but not in AT2 cells (0.13% and 0.08% vs. 0.03%; P = 0.94 and P = 0.44). Pulmonary expression of ACE was decreased in both COVID-19-related and -unrelated ARDS (P = 0.057 and P = 0.032). Similar increases in ACE2 and decreases in ACE were observed in sera of COVID-19 (P = 0.0054 and P < 0.0001) and non-COVID-19 ARDS (P < 0.0001 and P = 0.016). In addition, AT2 cells were decreased in patients with COVID-19-related ARDS compared with COVID-19-unrelated ARDS (1.395% vs. 2.94%, P = 0.0033). Conclusions: ACE2 is upregulated in lung tissue and serum of both COVID-19-related and -unrelated ARDS, whereas a loss of AT2 cells is selectively observed in COVID-19-related ARDS.

中文翻译：

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在 COVID-19 相关的急性呼吸窘迫综合征中血管紧张素转换酶 2 增加和肺泡 II 型细胞丢失。

基本原理：ACE2（血管紧张素转换酶 2）是严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的进入受体，在 2 型肺泡上皮细胞 (AT2) 中表达，可能在损伤后修复中起关键作用。ACE2 和 ACE 之间的不平衡也被假设为导致肺损伤。目的：表征 ACE2 和 ACE 的表达和分布，并将 AT2 与冠状病毒病（COVID-19）相关或无关的急性呼吸窘迫综合征（ARDS）和对照中的内皮细胞表达进行比较。方法：在两个不同的患者队列中回顾性测定肺组织染色（使用多重免疫荧光）和血清 ACE 浓度。肺组织中的 AT2 和内皮细胞分别被染色为 ProSPC（前表面活性剂蛋白 C）和 CD31。测量和主要结果：COVID-19 相关和非相关 ARDS 患者的肺 ACE2 表达增加（组织面积的 0.06% 和对照组的 0.12% 与 0.006%；分别为 P = 0.013 和 P < 0.0001）。ACE2 在内皮细胞中上调（0.32% 和 0.53% 与 0.01%；P = 0.009 和 P < 0.0001），但在 AT2 细胞中未上调（0.13% 和 0.08% 与 0.03%；P = 0.94 和 P = 0.44）。在 COVID-19 相关和非相关 ARDS 中，ACE 的肺表达均降低（P = 0.057 和 P = 0.032）。在 COVID-19（P = 0.0054 和 P < 0.0001）和非 COVID-19 ARDS（P < 0.0001 和 P = 0.016）的血清中观察到类似的 ACE2 增加和 ACE 减少。此外，与 COVID-19 无关的 ARDS 患者相比，COVID-19 相关的 ARDS 患者的 AT2 细胞减少（1.395% 对 2.94%，P = 0.0033）。结论：