Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Département d'Immunologie, Paris, France.
Front Cell Infect Microbiol. 2023 Jun 5;13:1165756. doi: 10.3389/fcimb.2023.1165756. eCollection 2023.
Increasing evidence has shown that coronavirus disease 19 (COVID-19) severity is driven by a dysregulated immunological response. Previous studies have demonstrated that natural killer (NK) cell dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of NK cell markers as a driver of death in the most critically ill patients.
We enrolled 50 non-vaccinated hospitalized patients infected with the initial virus or the alpha variant of SARS-CoV-2 with moderate or severe illness, to evaluate phenotypic and functional features of NK cells.
Here, we show that, consistent with previous studies, evolution NK cells from COVID-19 patients are more activated, with the decreased activation of natural cytotoxicity receptors and impaired cytotoxicity and IFN-γ production, in association with disease regardless of the SARS-CoV-2 strain. Fatality was observed in 6 of 17 patients with severe disease; NK cells from all of these patients displayed a peculiar phenotype of an activated memory-like phenotype associated with massive TNF-α production.
These data suggest that fatal COVID-19 infection is driven by an uncoordinated inflammatory response in part mediated by a specific subset of activated NK cells.
越来越多的证据表明，新型冠状病毒病 19（COVID-19）的严重程度是由免疫反应失调引起的。先前的研究表明，自然杀伤（NK）细胞功能障碍是 COVID-19 患者重病的基础，但缺乏对 NK 细胞标志物作为最危重患者死亡驱动因素的深入分析。
我们招募了 50 名未接种疫苗的住院感染 SARS-CoV-2 初始病毒或阿尔法变异株的中度或重度疾病患者，以评估 NK 细胞的表型和功能特征。
在这里，我们表明，与先前的研究一致，COVID-19 患者的 NK 细胞更具活性，自然细胞毒性受体的激活减少，细胞毒性和 IFN-γ产生受损，与疾病相关，而与 SARS-CoV-2 株无关。17 名重症患者中有 6 人死亡；所有这些患者的 NK 细胞均表现出一种独特的表型，即与大量 TNF-α产生相关的激活记忆样表型。
这些数据表明，致命性 COVID-19 感染是由部分由特定的激活 NK 细胞亚群介导的不协调的炎症反应驱动的。
