In patients with COVID-19, type 2 diabetes mellitus (T2DM) can impair the function of nasal-associated lymphoid tissue (NALT) and result in olfactory dysfunction. Exploring the causative alterations of T2DM within the nasal mucosa and NALT could provide insight into the pathogenic mechanisms and bridge the gap between innate immunity and adaptive immunity for virus clearance. Here, we designed a case-control study to compare the olfactory function (OF) among the groups of normal control (NC), COVID-19 mild pneumonia (MP), and MP patients with T2DM (MPT) after a 6-8 months’ recovery, in which MPT had a higher risk of hyposmia than MP and NC. No significant difference was found between the MP and NC. This elevated risk of hyposmia indicated that T2DM increased COVID-19 susceptibility in the nasal cavity with unknown causations. Therefore, we used the T2DM animal model (db/db mice) to evaluate how T2DM increased COVID-19 associated susceptibilities in the nasal mucosa and lymphoid tissues. Db/db mice demonstrated upregulated microvasculature ACE2 expression and significant alterations in lymphocytes component of NALT. Specifically, db/db mice NALT had increased immune-suppressive TCRγδ^±CD4^-CD8^- T and decreased immune-effective CD4^±/CD8^±TCRβ^± T cells and decreased mucosa-protective CD19^± B cells. These results indicated that T2DM could dampen the first-line defense of nasal immunity, and further mechanic studies of metabolic damage and NALT restoration should be one of the highest importance for COVID-19 healing.

在 COVID-19 患者中，2 型糖尿病 (T2DM) 会损害鼻相关淋巴组织 (NALT) 的功能并导致嗅觉功能障碍。探索鼻粘膜和 NALT 内 T2DM 的致病改变可以深入了解致病机制，并弥合先天免疫和适应性免疫之间的差距以清除病毒。在这里，我们设计了一项病例对照研究，以比较正常对照组 (NC)、COVID-19 轻度肺炎 (MP) 和患有 T2DM (MPT) 的 MP 患者在 6-8 个月后的嗅觉功能 (OF) ' 恢复，其中 MPT 比 MP 和 NC 有更高的嗅觉减退风险。MP 和 NC 之间没有发现显着差异。这种嗅觉减退的风险升高表明，T2DM 增加了鼻腔中 COVID-19 的易感性，原因不明。因此，我们使用 T2DM 动物模型（db/db 小鼠）来评估 T2DM 如何增加鼻粘膜和淋巴组织中与 COVID-19 相关的易感性。Db/db 小鼠表现出上调的微血管 ACE2 表达和 NALT 淋巴细胞成分的显着改变。具体而言，db/db 小鼠 NALT 增加了免疫抑制性 TCRγδ ^±CD4 ^- CD8 ^- T 和免疫有效 CD4 ^± /CD8 ^± TCRβ ^± T 细胞减少，粘膜保护性 CD19 ^± B 细胞减少。这些结果表明，T2DM 可以削弱鼻腔免疫的一线防御，进一步研究代谢损伤和 NALT 恢复的机制应该是 COVID-19 治愈的最重要因素之一。