We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19 in Europe. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2–3-fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in γδ T cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a pro-inflammatory cytokine storm, Th1 and Th2 activation, and markers of T cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response. The investigation was conducted as part of an overall French clinical cohort assessing patients with COVID-19 and registered in clinicaltrials.gov under the following number: NCT04262921.

我们报告了与致命病例在欧洲致命病例相关的免疫应答的纵向分析。该患者表现出向多器官衰竭的快速发展。尽管进行了抗病毒和免疫调节剂治疗，但仍在多个鼻咽，血液和胸膜样本中检测到SARS-CoV-2。血液中的临床演变过程以表达力竭（PD-1）和衰老（CD57）标记的分化效应T细胞增加（2-3倍），分泌抗体的细胞扩展，增加15倍为特征。 γδT细胞和正在增殖的NK细胞群体，以及单核细胞的总消失，提示肺运输。在血清中，有促炎性细胞因子风暴，Th1和Th2激活以及T细胞衰竭，凋亡，细胞毒性的标志物，观察到内皮细胞的活化直到致命的结果。该病例强调需要进行精心设计的研究，以研究辅助方法以控制病毒复制，高炎症状态的来源以及针对病理生理反应的免疫调节。该调查是对法国整体临床队列进行评估的一部分，该队列对COVID-19患者进行了评估，并在以下临床编号中注册：nct04262921。