Venegoni Chiara, Raineri Davide, Mazzucca Camilla Barbero, Ghazanfar Ali, Cappellano Giuseppe, Baricich Alessio, Patrucco Filippo, Zeppegno Patrizia, Gramaglia Carla, Balbo Piero Emilio, Cantaluppi Vincenzo, Patti Giuseppe, Giordano Mara, Manfredi Marcello, Rolla Roberta, Sainaghi Pier Paolo, Pirisi Mario, Bellan Mattia, Chiocchetti Annalisa
Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases-IRCAD, University of Eastern Piedmont 28100 Novara, Italy; Center for Translational Research on Autoimmune and Allergic Diseases, University of Eastern Piedmont 28100 Novara, Italy.
Translational Medicine Department, University of Eastern Piedmont, Novara, Italy.
Int Immunopharmacol. 2025 Feb 20;148:114103. doi: 10.1016/j.intimp.2025.114103. Epub 2025 Jan 27.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to widespread post-acute sequelae of COVID-19 (PASC), affecting multiple body systems. Despite its prevalence, PASC's pathogenesis remains unclear, with hypotheses suggesting viral persistence, immune activation, and autoimmune responses among the pathogenetic mechanism. This study aimed to evaluate T cell memory response in PASC patients, one year post-hospital discharge and correlate it with clinical parameters to identify a potential PASC-associated fingerprint.
Peripheral blood mononuclear cells (PBMCs) from PASC patients and healthy controls (HC) were stimulated with a pool of spike peptides. CD4 and CD8 T cell responses were evaluated by flow cytometry using the activation-induced markers assay (AIM).
Findings showed significant activation of the CD4 T cell compartment, with a higher proportion of responders among PASC patients. Central memory (CM) T cells expressing pro-inflammatory cytokines were more prevalent in responders. Clinical correlations revealed higher SARS-CoV-2-specific T cell responses in patients with reduced diffuse lung capacity for carbon monoxide (DLCO) and residual symptoms.
These immune changes, especially in CM T cells, could play a pivotal role in PASC's development and persistence, impacting patients' daily lives.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）导致了广泛的新冠病毒感染后急性后遗症（PASC），影响多个身体系统。尽管其普遍存在，但PASC的发病机制仍不清楚，假说认为发病机制包括病毒持续存在、免疫激活和自身免疫反应。本研究旨在评估PASC患者出院一年后的T细胞记忆反应，并将其与临床参数相关联，以确定潜在的PASC相关特征。
用一组刺突肽刺激PASC患者和健康对照（HC）的外周血单个核细胞（PBMC）。使用激活诱导标志物检测法（AIM）通过流式细胞术评估CD⁺4和CD⁺8 T细胞反应。
研究结果显示CD⁺4 T细胞区室有显著激活，PASC患者中反应者比例更高。表达促炎细胞因子的中央记忆（CM）T细胞在反应者中更为普遍。临床相关性分析显示，一氧化碳弥散量（DLCO）降低和有残留症状的患者中，SARS-CoV-2特异性T细胞反应更高。
这些免疫变化，尤其是CM T细胞中的变化，可能在PASC的发生和持续发展中起关键作用，影响患者的日常生活。
