Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, P.R. China.
Eur Rev Med Pharmacol Sci. 2021 Jan;25(1):527-540. doi: 10.26355/eurrev_202101_24425.
The pathogenesis of coronavirus disease 2019 (COVID-19) remains clear, and no effective treatment exists. SARS-CoV-2 is the virus that causes COVID-19 and uses ACE2 as a cell receptor to invade human cells. Therefore, ACE2 is a key factor to analyze the SARS-CoV-2 infection mechanism.
We included 9,783 sequencing results of different organs, analyzed the effects of different ACE2 expression patterns in organs and immune regulation.
We found that ACE2 expression was significantly increased in the lungs and digestive tract. The cellular immunity of individuals with elevated ACE2 expression is activated, whereas humoral immunity is dampened, leading to the release of many inflammatory factors dominated by IL6. Furthermore, by studying the sequencing results of SARS-CoV-2-infected and uninfected cells, IL6 was found to be an indicator of a significant increase in the number of infected cells. However, although patients with high expression of ACE2 will release many inflammatory factors dominated by IL6, cellular immunity in the colorectum is significantly activated. This effect may explain why individuals with SARS-CoV-2 infection have severe lung symptoms and digestion issues, which are important causes of milder symptoms.
This finding indicates that ACE2 and IL6 inhibitors have important value in COVID-19.
新型冠状病毒肺炎（COVID-19）的发病机制尚不清楚，目前尚无有效的治疗方法。SARS-CoV-2 是引起 COVID-19 的病毒，它使用 ACE2 作为细胞受体入侵人体细胞。因此，ACE2 是分析 SARS-CoV-2 感染机制的关键因素。
我们纳入了 9783 个不同器官的测序结果，分析了器官和免疫调节中 ACE2 不同表达模式的影响。
我们发现 ACE2 在肺部和消化道中的表达显著增加。表达升高的个体的细胞免疫被激活，而体液免疫受到抑制，导致以 IL6 为主的许多炎症因子释放。此外，通过研究 SARS-CoV-2 感染和未感染细胞的测序结果，发现 IL6 是感染细胞数量显著增加的指标。然而，尽管 ACE2 高表达的患者会释放许多以 IL6 为主的炎症因子，但结直肠中的细胞免疫明显被激活。这一效应可能解释了为什么 SARS-CoV-2 感染的个体肺部症状严重，同时伴有消化系统问题，这是症状较轻的重要原因。
这一发现表明 ACE2 和 IL6 抑制剂在 COVID-19 中具有重要价值。
