Suzuki Rigel, Ono Yuki, Noshita Koji, Kim Kwang Su, Ito Hayato, Morioka Yuhei, Tamura Tomokazu, Okuzaki Daisuke, Tagawa Tetsuzo, Takenaka Tomoyoshi, Yoshizumi Tomoharu, Shimamura Teppei, Iwami Shingo, Fukuhara Takasuke
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
Department of Surgery and Science, Graduate School of Medicine, Kyushu University, Fukuoka, Fukuoka, Japan.
Microbiol Immunol. 2023 Jan;67(1):22-31. doi: 10.1111/1348-0421.13034. Epub 2022 Nov 2.
Smoking is one of the risk factors most closely related to the severity of coronavirus disease 2019 (COVID-19). However, the relationship between smoking history and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is unknown. In this study, we evaluated the ACE2 expression level in the lungs of current smokers, ex-smokers, and nonsmokers. The ACE2 expression level of ex-smokers who smoked cigarettes until recently (cessation period shorter than 6 months) was higher than that of nonsmokers and ex-smokers with a long history of nonsmoking (cessation period longer than 6 months). We also showed that the efficiency of SARS-CoV-2 infection was enhanced in a manner dependent on the angiotensin-converting enzyme 2 (ACE2) expression level. Using RNA-seq analysis on the lungs of smokers, we identified that the expression of inflammatory signaling genes was correlated with ACE2 expression. Notably, with increasing duration of smoking cessation among ex-smokers, not only ACE2 expression level but also the expression levels of inflammatory signaling genes decreased. These results indicated that smoking enhances the expression levels of ACE2 and inflammatory signaling genes. Our data suggest that the efficiency of SARS-CoV-2 infection is enhanced by smoking-mediated upregulation of ACE2 expression level.
吸烟是与2019冠状病毒病（COVID-19）严重程度最密切相关的风险因素之一。然而，吸烟史与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染性之间的关系尚不清楚。在本研究中，我们评估了当前吸烟者、既往吸烟者和非吸烟者肺组织中血管紧张素转换酶2（ACE2）的表达水平。近期仍在吸烟（戒烟时间短于6个月）的既往吸烟者的ACE2表达水平高于非吸烟者和长期戒烟（戒烟时间长于6个月）的既往吸烟者。我们还表明，SARS-CoV-2感染效率以依赖血管紧张素转换酶2（ACE2）表达水平的方式增强。通过对吸烟者肺组织进行RNA测序分析，我们发现炎症信号基因的表达与ACE2表达相关。值得注意的是，随着既往吸烟者戒烟时间的延长，不仅ACE2表达水平降低，炎症信号基因的表达水平也降低。这些结果表明，吸烟会提高ACE2和炎症信号基因的表达水平。我们的数据表明，吸烟介导的ACE2表达水平上调会增强SARS-CoV-2的感染效率。
