Gao Yu, Cai Curtis, Adamo Sarah, Biteus Elsa, Kamal Habiba, Dager Lena, Miners Kelly L, Llewellyn-Lacey Sian, Ladell Kristin, Amratia Pragati S, Bentley Kirsten, Kollnberger Simon, Wu Jinghua, Akhirunnesa Mily, Jones Samantha A, Julin Per, Lidman Christer, Stanton Richard J, Goepfert Paul A, Peluso Michael J, Deeks Steven G, Davies Helen E, Aleman Soo, Buggert Marcus, Price David A
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, Basel, Switzerland.
Nat Immunol. 2025 May;26(5):692-705. doi: 10.1038/s41590-025-02135-5. Epub 2025 Apr 30.
Long coronavirus disease (COVID) is a heterogeneous clinical condition of uncertain etiology triggered by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we used ultrasensitive approaches to profile the immune system and the plasma proteome in healthy convalescent individuals and individuals with long COVID, spanning geographically independent cohorts from Sweden and the United Kingdom. Symptomatic disease was not consistently associated with quantitative differences in immune cell lineage composition or antiviral T cell immunity. Healthy convalescent individuals nonetheless exhibited higher titers of neutralizing antibodies against SARS-CoV-2 than individuals with long COVID, and extensive phenotypic analyses revealed a subtle increase in the expression of some co-inhibitory receptors, most notably PD-1 and TIM-3, among SARS-CoV-2 nonspike-specific CD8 T cells in individuals with long COVID. We further identified a shared plasma biomarker signature of disease linking breathlessness with apoptotic inflammatory networks centered on various proteins, including CCL3, CD40, IKBKG, IL-18 and IRAK1, and dysregulated pathways associated with cell cycle progression, lung injury and platelet activation, which could potentially inform the diagnosis and treatment of long COVID.
长期新冠病毒病（COVID）是一种病因不明的异质性临床病症，由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染引发。在此，我们采用超灵敏方法对康复个体和长期新冠患者的免疫系统及血浆蛋白质组进行分析，研究对象涵盖来自瑞典和英国的地理上独立的队列。有症状的疾病与免疫细胞谱系组成或抗病毒T细胞免疫的定量差异并无一致关联。然而，康复个体针对SARS-CoV-2的中和抗体滴度高于长期新冠患者，广泛的表型分析显示，在长期新冠患者中，SARS-CoV-2非刺突特异性CD8 T细胞中某些共抑制受体（最显著的是PD-1和TIM-3）的表达略有增加。我们进一步确定了一种疾病的共享血浆生物标志物特征，该特征将呼吸困难与以包括CCL3、CD40、IKBKG、IL-18和IRAK1在内的多种蛋白质为中心的凋亡炎症网络以及与细胞周期进程、肺损伤和血小板活化相关的失调途径联系起来，这可能为长期新冠的诊断和治疗提供依据。
