Abstract Mucosal-associated invariant T (MAIT) cells are an abundant population of unconventional T cells in humans and play important roles in immune defense against microbial infections. Severe COVID-19 is associated with strong activation of MAIT cells and loss of these cells from circulation. In the present study, we investigated the capacity of MAIT cells to recover after severe COVID-19. In longitudinal paired analysis, MAIT cells initially rebounded numerically and phenotypically in most patients at 4 mo postrelease from the hospital. However, the rebounding MAIT cells displayed signs of persistent activation with elevated expression of CD69, CD38, and HLA-DR. Although MAIT cell function was restored in many patients, a subgroup displayed a predominantly PD-1high functionally impaired MAIT cell pool. This profile was associated with poor expression of IFN-γ and granzyme B in response to IL-12+IL-18 and low levels of polyfunctionality. Unexpectedly, although the overall T cell counts recovered, normalization of the MAIT cell pool failed at 9-mo follow-up, with a clear decline in MAIT cell numbers and a further increase in PD-1 levels. Together, these results indicate an initial transient period of inconsistent recovery of MAIT cells that is not sustained and eventually fails. Persisting MAIT cell impairment in previously hospitalized patients with COVID-19 may have consequences for antimicrobial immunity and inflammation and could potentially contribute to post-COVID-19 health problems.

中文翻译：

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严重 COVID-19 后的动态 MAIT 细胞恢复是短暂的，并有异质功能异常的迹象

摘要粘膜相关不变 T (MAIT) 细胞是人体中数量丰富的非常规 T 细胞群，在抵抗微生物感染的免疫防御中发挥着重要作用。严重的 COVID-19 与 MAIT 细胞的强烈激活和这些细胞从循环中的损失有关。在本研究中，我们研究了 MAIT 细胞在严重的 COVID-19 后恢复的能力。在纵向配对分析中，大多数患者在出院后 4 个月时，MAIT 细胞在数量和表型上最初出现反弹。然而，反弹的 MAIT 细胞显示出持续激活的迹象，CD69、CD38 和 HLA-DR 表达升高。尽管许多患者的 MAIT 细胞功能得到恢复，但有一个亚组显示主要为 PD-1 高功能受损的 MAIT 细胞库。该谱与响应 IL-12+IL-18 的 IFN-γ 和颗粒酶 B 低表达以及低水平的多功能性相关。出乎意料的是，尽管总体T细胞计数恢复，但MAIT细胞池的正常化在9个月的随访中失败，MAIT细胞数量明显下降，PD-1水平进一步升高。总之，这些结果表明 MAIT 细胞恢复不一致的初始短暂期不能持续并最终失败。先前住院的 COVID-19 患者中持续存在的 MAIT 细胞损伤可能会对抗菌免疫和炎症产生影响，并可能导致 COVID-19 后的健康问题。