Université Paris 7 Denis Diderot, UMR 1160 INSERM, Paris, France.
Université de Lorraine, CHRU-Nancy, Laboratoire d'Immunologie, Nancy, France.
Front Immunol. 2020 Oct 23;11:580250. doi: 10.3389/fimmu.2020.580250. eCollection 2020.
Little is known about the time-dependent immune responses in severe COVID-19. Data of 15 consecutive patients were sequentially recorded from intensive care unit admission. Lymphocyte subsets and total monocyte and subsets counts were monitored as well as the expression of HLA-DR. For 5 patients, SARS-CoV-2-specific T-cell polyfunctionality was assessed against Spike and Nucleoprotein SARS-CoV-2 peptides. Non-specific inflammation markers were increased in all patients. Median monocyte HLA-DR expression was below the 8,000 AB/C threshold defining acquired immunodepression. A "V" trend curve for lymphopenia, monocyte numbers, and HLA-DR expression was observed with a nadir between days 11 and 14 after symptoms' onset. Intermediate CD14CD16 monocytes increased early with a reduction in classic CD14CD16 monocytes. Polyfunctional SARS-Cov-2-specific CD4 T-cells were present and functional, whereas virus-specific CD8 T-cells were less frequent and not efficient. We report a temporal variation of both innate and adaptive immunity in severe COVID-19 patients, helpful in guiding therapeutic decisions (e.g. anti-inflammatory immunostimulatory ones). We describe a defect in virus-specific CD8 T-cells, a potential biomarker of clinical severity. These combined data also provide helpful knowledge for vaccine design.
https://clinicaltrials.gov/, identifier NCT04386395.
关于严重 COVID-19 的时间依赖性免疫反应知之甚少。从重症监护病房入院开始，连续记录了 15 名连续患者的数据。监测了淋巴细胞亚群和总单核细胞及其亚群计数，以及 HLA-DR 的表达。对于 5 名患者，评估了针对 Spike 和 Nucleoprotein SARS-CoV-2 肽的 SARS-CoV-2 特异性 T 细胞多功能性。所有患者的非特异性炎症标志物均增加。单核细胞 HLA-DR 表达中位数低于定义获得性免疫抑制的 8000AB/C 阈值。在症状发作后 11 至 14 天之间，观察到淋巴细胞减少、单核细胞数量和 HLA-DR 表达的“V”趋势曲线，最低点。中间 CD14CD16 单核细胞早期增加，经典 CD14CD16 单核细胞减少。存在且功能正常的多能 SARS-CoV-2 特异性 CD4 T 细胞，而病毒特异性 CD8 T 细胞较少且效率较低。我们报告了严重 COVID-19 患者固有免疫和适应性免疫的时间变化，有助于指导治疗决策（例如抗炎免疫刺激剂）。我们描述了病毒特异性 CD8 T 细胞的缺陷，这可能是临床严重程度的生物标志物。这些综合数据还为疫苗设计提供了有用的知识。
https://clinicaltrials.gov/，标识符 NCT04386395。
