Immune cell responses are strikingly altered in patients with severe coronavirus disease 2019 (COVID-19), but the immunoregulatory process in these individuals is not fully understood. In this study, 23 patients with mild and 22 patients with severe COVID-19 and 6 asymptomatic carriers of COVID-19 were enrolled, along with 44 healthy controls (HC). Peripheral immune cells in HC and patients with COVID-19 were comprehensively profiled using mass cytometry. We found that in patients with severe COVID-19, the number of HLA-DR^low/− monocytes was significantly increased, but that of mucosal-associated invariant T (MAIT) cells was greatly reduced. MAIT cells were highly activated but functionally impaired in response to Escherichia coli and IL-12/IL-18 stimulation in patients with severe COVID-19, especially those with microbial coinfection. Single-cell transcriptome analysis revealed that IFN-stimulated genes were significantly upregulated in peripheral MAIT cells and monocytes from patients with severe COVID-19. IFN-α pretreatment suppressed MAIT cells’ response to E. coli by triggering high levels of IL-10 production by HLA-DR^low/−–suppressive monocytes. Blocking IFN-α or IL-10 receptors rescued MAIT cell function in patients with severe COVID-19. Moreover, plasma from patients with severe COVID-19 inhibited HLA-DR expression by monocytes through IL-10. These data indicate a unique pattern of immune dysregulation in severe COVID-19, which is characterized by enrichment of suppressive HLA-DR^low/− monocytes associated with functional impairment of MAIT cells through the IFN/IL-10 pathway.

2019 年严重冠状病毒病 (COVID-19) 患者的免疫细胞反应发生了显着变化，但尚未完全了解这些人的免疫调节过程。在这项研究中，纳入了 23 名轻度 COVID-19 患者和 22 名重度 COVID-19 患者和 6 名无症状 COVID-19 携带者，以及 44 名健康对照（HC）。HC 和 COVID-19 患者的外周免疫细胞使用质谱仪进行了全面分析。我们发现，在重症 COVID-19 患者中，HLA-DR^低/-单核细胞的数量显着增加，但黏膜相关不变 T (MAIT) 细胞的数量却大大减少。MAIT 细胞高度活化但功能受损以响应大肠杆菌和 IL-12/IL-18 刺激严重 COVID-19 患者，尤其是那些有微生物合并感染的患者。单细胞转录组分析显示，严重 COVID-19 患者的外周 MAIT 细胞和单核细胞中 IFN 刺激的基因显着上调。IFN-α 预处理通过触发 HLA-DR^低/-抑制性单核细胞产生高水平的 IL-10来抑制 MAIT 细胞对大肠杆菌的反应。阻断 IFN-α 或 IL-10 受体可挽救重症 COVID-19 患者的 MAIT 细胞功能。此外，来自严重 COVID-19 患者的血浆通过 IL-10 抑制单核细胞的 HLA-DR 表达。这些数据表明严重 COVID-19 中免疫失调的独特模式，其特征是抑制性 HLA-DR 的富集^低/- 单核细胞通过 IFN/IL-10 途径与 MAIT 细胞的功能损伤相关。