Severe COVID-19 is characterized by excessive inflammation of the lower airways. The balance of protective versus pathological immune responses in COVID-19 is incompletely understood. Mucosa-associated invariant T (MAIT) cells are antimicrobial T cells that recognize bacterial metabolites, and can also function as innate-like sensors and mediators of antiviral responses. Here, we investigated the MAIT cell compartment in COVID-19 patients with moderate and severe disease, as well as in convalescence. We show profound and preferential decline in MAIT cells in the circulation of patients with active disease paired with strong activation. Furthermore, transcriptomic analyses indicated significant MAIT cell enrichment and pro-inflammatory IL-17A bias in the airways. Unsupervised analysis identified MAIT cell CD69^high and CXCR3^low immunotypes associated with poor clinical outcome. MAIT cell levels normalized in the convalescent phase, consistent with dynamic recruitment to the tissues and later release back into the circulation when disease is resolved. These findings indicate that MAIT cells are engaged in the immune response against SARS-CoV-2 and suggest their possible involvement in COVID-19 immunopathogenesis.

严重的 COVID-19 的特点是下呼吸道过度炎症。COVID-19 中保护性免疫反应与病理性免疫反应的平衡尚不完全清楚。粘膜相关不变 T (MAIT) 细胞是识别细菌代谢物的抗菌 T 细胞，也可以充当抗病毒反应的先天传感器和介质。在这里，我们研究了患有中度和重度疾病以及恢复期的 COVID-19 患者的 MAIT 细胞区室。我们发现，患有活动性疾病的患者循环中 MAIT 细胞发生显着且优先的下降，同时伴有强烈的激活。此外，转录组分析表明气道中有显着的 MAIT 细胞富集和促炎性 IL-17A 偏向。无监督分析发现 MAIT 细胞 CD69^高免疫型和 CXCR3^低免疫型与不良临床结果相关。MAIT 细胞水平在恢复期恢复正常，与组织的动态募集一致，并在疾病解决后释放回循环系统。这些发现表明 MAIT 细胞参与针对 SARS-CoV-2 的免疫反应，并表明它们可能参与了 COVID-19 的免疫发病机制。