Mouton William, Djebali Sophia, Villard Marine, Allatif Omran, Chauvel Cécile, Benezech Sarah, Vanhems Philippe, Marvel Jacqueline, Walzer Thierry, Trouillet-Assant Sophie
Laboratoire commun de recherche HCL-bioMérieux, Hospices Civils de Lyon, Lyon, France.
Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Lyon, France.
Eur J Immunol. 2025 Jul;55(7):e51948. doi: 10.1002/eji.202551948.
Post-acute sequelae of COVID-19 (PASC) are a complex clinical condition that requires a better understanding of its underlying biological mechanisms. In this study, we assessed hundreds of virological, serological, immunological, and tissue damage biomarkers in two cohorts of patients who had experienced either mild (n = 270) or severe (n = 188) COVID-19, 6 to 9 months post-initial infection, and in which 40% and 57.4% of patients, respectively, developed PASC. Blood analysis showed that the main differences observed in humoral, viral, and biological biomarkers were associated with the initial COVID-19 severity, rather than being specifically linked to PASC. However, patients with PASC displayed altered CD4 and CD8 memory T cell subsets, with higher cytokine-secreting cells and increased terminally differentiated CD45RA effector memory T cells (TEMRA). Elevated SARS-CoV-2-specific T cells responsive to nucleocapsid/membrane proteins with a TEMRA phenotype were also observed. A random forest model identified these features and initial symptom duration as top variables discriminating PASC, achieving over 80% classification accuracy.
新冠后遗症（PASC）是一种复杂的临床病症，需要更好地了解其潜在的生物学机制。在本研究中，我们评估了两组感染新冠病毒的患者的数百种病毒学、血清学、免疫学和组织损伤生物标志物，这两组患者分别为轻症（n = 270）和重症（n = 188）患者，在初次感染后6至9个月，其中分别有40%和57.4%的患者出现了PASC。血液分析表明，在体液、病毒和生物标志物方面观察到的主要差异与初次感染新冠时的严重程度有关，而非与PASC有特定关联。然而，患有PASC的患者表现出CD4和CD8记忆T细胞亚群的改变，分泌细胞因子的细胞增多，终末分化的CD45RA效应记忆T细胞（TEMRA）增加。还观察到对核衣壳/膜蛋白有反应的、具有TEMRA表型的新冠病毒特异性T细胞升高。一个随机森林模型将这些特征和初始症状持续时间确定为区分PASC的首要变量，分类准确率超过80%。
