Cystic fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene. Although viral respiratory tract infections are, in general, more severe in patients with CF compared with the general population, a small number of studies indicate that SARS-CoV-2 does not cause a worse infection in CF. This is surprising since comorbidities including preexisting lung disease have been reported to be associated with worse outcomes in SARS-CoV-2 infections. Several recent studies provide insight into why SARS-CoV-2 may not produce more severe outcomes in CF. First, ACE and ACE2, genes that play key roles in SARS-CoV-2 infection, have some variants that are predicted to reduce the severity of SARS-CoV-2 infection. Second, mRNA for ACE2 is elevated and mRNA for TMPRSS2, a serine protease, is decreased in CF airway epithelial cells. Increased ACE2 is predicted to enhance SARS-CoV-2 binding to cells but would increase conversion of angiotensin II, which is proinflammatory, to angiotensin-1–7, which is anti-inflammatory. Thus, increased ACE2 would reduce inflammation and lung damage due to SARS-CoV-2. Moreover, decreased TMPRSS2 would reduce SARS-CoV-2 entry into airway epithelial cells. Second, many CF patients are treated with azithromycin, which suppresses viral infection and lung inflammation and inhibits the activity of furin, a serine protease. Finally, the CF lung contains high levels of serine protease inhibitors including ecotin and SERPINB1, which are predicted to reduce the ability of TMPRSS2 to facilitate SARS-CoV-2 entry into airway epithelial cells. Thus, a variety of factors may mitigate the severity of SARS-CoV-2 in CF.

中文翻译：

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SARS-CoV-2 (COVID-19) 和囊性纤维化。

囊性纤维化（CF）是一种由CFTR基因突变引起的遗传性疾病。尽管与一般人群相比，CF 患者的病毒性呼吸道感染一般更为严重，但少数研究表明 SARS-CoV-2 不会导致 CF 感染更严重。这是令人惊讶的，因为据报道，包括先前存在的肺部疾病在内的合并症与 SARS-CoV-2 感染的较差结果有关。最近的几项研究深入了解了为什么 SARS-CoV-2 可能不会在 CF 中产生更严重的结果。首先，ACE和ACE2是在 SARS-CoV-2 感染中发挥关键作用的基因，它们具有一些变异体，预计可以降低 SARS-CoV-2 感染的严重程度。其次，CF 气道上皮细胞中ACE2的 mRNA升高，而TMPRSS2（一种丝氨酸蛋白酶）的 mRNA 降低。ACE2 的增加预计会增强 SARS-CoV-2 与细胞的结合，但会增加促炎性血管紧张素 II 向抗炎性血管紧张素 1-7 的转化。因此，增加 ACE2 将减少 SARS-CoV-2 引起的炎症和肺部损伤。此外，TMPRSS2 减少会减少 SARS-CoV-2 进入气道上皮细胞。其次，许多CF患者接受阿奇霉素治疗，阿奇霉素可以抑制病毒感染和肺部炎症，并抑制弗林蛋白酶（一种丝氨酸蛋白酶）的活性。最后，CF肺含有高水平的丝氨酸蛋白酶抑制剂，包括大肠杆菌素和SERPINB1，预计它们会降低TMPRSS2促进SARS-CoV-2进入气道上皮细胞的能力。因此，多种因素可能会减轻 CF 中 SARS-CoV-2 的严重程度。