Background: The role of cellular immunity in pathogenesis of COVID-19 is unclear and conflicting data points to insufficient or pathogenic immunity as drivers of COVID-19 progression. Here we aimed to delineate the phenotype and function of the immune system in patients with moderate, severe, and critical COVID-19. Methods: In this prospective study, we included 53 patients with moderate (n=21), severe (n=18), and critical (n=14) COVID-19 manifestations. Using multiparametric flow cytometry we compared quantitative, phenotypic, and functional characteristics of circulating immune cells, SARS-CoV-2 antigen-reactive T-cells, and humoral immunity. Results: Deep phenotypic profiling revealed a depletion of circulating bulk CD8+ T-cells, CD4+ and CD8+ T-cell subsets with activated memory/effector T-cells expressing CD57+, HLA-DR+, and the key activation and migration molecule CD11a++ in critical COVID-19. Importantly, survival from acute respiratory distress syndrome was accompanied by a recovery of the depleted CD11++ T-cell subsets including T-cells expressing CD28, CD57, HLA-DR activation/effector molecules. We further observed a stronger response of S-protein specific T-cells producing inflammatory cytokines in critical COVID-19 cases. This seemingly contradictory observation is in fact confirmation of the underlying immunopathogenesis in patients with critical COVID-19. Conclusion: Our findings suggest a CD11a-based immune signature as a possible prognostic marker for disease development. Our data further reveal that increased rather than decreased SARS-CoV-2 specific T cell immunity is associated with adverse outcome in COVID-19. Tissue migration of activated effectors T-cells may constitute a crucial cornerstone in the immunopathogenesis of SARS-CoV-2 associated tissue injury.

中文翻译：

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COVID-19进展可能由T细胞免疫发病机制驱动

背景：目前尚不清楚细胞免疫在COVID-19发病机理中的作用，并且相互矛盾的数据表明，不足以作为COVID-19进展的驱动力或致病性免疫。在这里，我们旨在描述中度，重度和严重COVID-19患者的免疫系统表型和功能。方法：在这项前瞻性研究中，我们纳入了53例中度（n = 21），严重（n = 18）和严重（n = 14）COVID-19表现的患者。使用多参数流式细胞仪，我们比较了循环免疫细胞，SARS-CoV-2抗原反应性T细胞和体液免疫的定量，表型和功能特征。结果：深表型分析显示，循环中的大量CD8 + T细胞，CD4 +和CD8 + T细胞亚群耗竭，而活化的记忆/效应T细胞表达CD57 +，HLA-DR +，以及关键COVID-19中的关键激活和迁移分子CD11a ++。重要的是，急性呼吸窘迫综合征的生存伴随着衰竭的CD11 ++ T细胞亚群的恢复，其中包括表达CD28，CD57，HLA-DR激活/效应分子的T细胞。我们还观察到在关键的COVID-19病例中，S蛋白特异性T细胞产生炎性细胞因子的反应更强。这种看似矛盾的观察结果实际上证实了关键性COVID-19患者潜在的免疫发病机制。结论：我们的发现提示，基于CD11a的免疫信号可能是疾病发展的预后标志。我们的数据进一步表明，SARS-CoV-2特异性T细胞免疫力的升高而非降低与COVID-19的不良预后相关。