Department of Internal Medicine 3, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Arthritis Res Ther. 2021 Jun 10;23(1):166. doi: 10.1186/s13075-021-02464-4.
To investigate whether methotrexate treatment may affect the susceptibility to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Clinical assessment of symptoms, SARS-CoV-2 RNA, and anti-SARS-CoV-2 IgG in an initial case series of four families and confirmatory case series of seven families, within which one family member developed coronavirus disease 19 (COVID-19) and exposed another family member receiving methotrexate treatment; experimental part with methotrexate treatment of mice and organoids followed by the assessment of mRNA and protein expression of the SARS-CoV-2 receptor angiotensin-converting enzyme (ACE)-2.
In the initial case series, three of four women on a joint ski trip developed COVID-19, while the fourth woman, under treatment with methotrexate, remained virus-free. Two of the three diseased women infected their husbands, while the third husband treated with methotrexate remained virus-free. In addition, 7 other families were identified in a follow-up case series, in which one member developed COVID-19, while the other, receiving methotrexate, remained healthy. Experimentally, when mice were treated with methotrexate, ACE2 expression significantly decreased in the lung, in the intestinal epithelium, and in intestinal organoids.
These clinical and experimental data indicate that methotrexate has certain protective effects on SARS-CoV-2 infection via downregulating ACE2.
为了研究甲氨蝶呤治疗是否会影响对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的易感性。
对四户家庭的初始病例系列和七户家庭的确诊病例系列中的症状、SARS-CoV-2 RNA 和抗 SARS-CoV-2 IgG 进行临床评估，其中一户家庭成员出现了冠状病毒病 19（COVID-19）并使接受甲氨蝶呤治疗的另一名家庭成员暴露于病毒之下；通过对接受甲氨蝶呤治疗的小鼠和类器官进行实验部分，评估 SARS-CoV-2 受体血管紧张素转换酶（ACE）-2 的 mRNA 和蛋白表达。
在初始病例系列中，四位一同滑雪的女性中有三位出现了 COVID-19，而第四位接受甲氨蝶呤治疗的女性则未感染病毒。三位患病女性中有两位感染了她们的丈夫，而第三位接受甲氨蝶呤治疗的丈夫则未感染病毒。此外，在后续的病例系列中还发现了另外 7 个家庭，其中一个成员出现了 COVID-19，而另一个接受甲氨蝶呤治疗的成员则保持健康。实验中，当用甲氨蝶呤治疗小鼠时，肺、肠道上皮和肠道类器官中的 ACE2 表达显著下降。
这些临床和实验数据表明，甲氨蝶呤通过下调 ACE2 对 SARS-CoV-2 感染具有一定的保护作用。
