Bendíčková Kamila, Papatheodorou Ioanna, Blažková Gabriela, Helán Martin, Haláková Michaela, Bednář Petr, Spearing Erin, Obermannová Lucie, Štíchová Julie, Heroldová Monika Dvořáková, Tomáš Tomáš, Panovský Roman, Šrámek Vladimír, De Zuani Marco, Vlková Marcela, Růžek Daniel, Hortová-Kohoutková Marcela, Frič Jan
International Clinical Research Center St. Anne's University Hospital Brno Czech Republic.
International Clinical Research Center, Faculty of Medicine Masaryk University Brno Czech Republic.
Clin Transl Immunology. 2025 Jun 27;14(7):e70041. doi: 10.1002/cti2.70041. eCollection 2025.
Several years after the COVID-19 pandemic, the impact of SARS-CoV-2 on immunity and the potential protective role of Bacillus Calmette-Guérin (BCG) vaccination through trained immunity remain a subject of investigation. This study aimed to determine the long-term impact of SARS-CoV-2 on immune cells and the association between BCG vaccination, latent infections and COVID-19 severity and sepsis progression.
We conducted a prospective analysis of patients who recovered from mild/severe/critical COVID-19 ( = 97, 3-17 months after COVID-19) and sepsis patients ( = 64). First, we assessed the impact of COVID-19 and its severity on immune cell frequencies and expression of functional markers. Further, we analysed plasma titres of anti-/cytomegalovirus/BCG antibodies and their association with COVID-19 severity and sepsis outcome. To examine monocyte responses to secondary challenge, monocytes isolated from COVID-19 convalescent patients, BCG vaccinated and unvaccinated volunteers were stimulated with SARS-CoV-2 and LPS.
Post-COVID-19 patients showed immune dysregulation regardless of disease severity characterised by altered expression of activation and functional markers in myeloid (CD39, CD64, CD85d, CD11b) and lymphoid cells (CD39, CD57, TIGIT). Strikingly, post-critical COVID-19 patients showed elevated expression of CD57 in CD8 T cells compared to other severity groups. A trend toward improved outcomes in BCG-seropositive COVID-19/sepsis patients was observed, although this may be confounded by age differences between groups. In contrast, the monocyte response to stimulation appeared unaffected by COVID-19 severity.
These findings highlight the long-term alterations of immune cells in post-COVID-19 patients, emphasising the substantial impact of COVID-19 on immune function.
在2019冠状病毒病大流行数年之后，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）对免疫的影响以及卡介苗（BCG）接种通过训练免疫发挥的潜在保护作用仍是研究课题。本研究旨在确定SARS-CoV-2对免疫细胞的长期影响以及BCG接种、潜伏感染与2019冠状病毒病严重程度和脓毒症进展之间的关联。
我们对从轻度/重度/危重型2019冠状病毒病康复的患者（n = 97，在感染2019冠状病毒病后3 - 17个月）和脓毒症患者（n = 64）进行了前瞻性分析。首先，我们评估了2019冠状病毒病及其严重程度对免疫细胞频率和功能标志物表达的影响。此外，我们分析了抗巨细胞病毒/BCG抗体的血浆滴度及其与2019冠状病毒病严重程度和脓毒症结局的关联。为了检测单核细胞对二次刺激的反应，用SARS-CoV-2和脂多糖刺激从2019冠状病毒病康复患者、接种BCG和未接种BCG的志愿者中分离出的单核细胞。
感染2019冠状病毒病后的患者无论疾病严重程度如何均表现出免疫失调，其特征为髓系细胞（CD39、CD64、CD85d、CD11b）和淋巴细胞（CD39、CD57、TIGIT）中激活和功能标志物的表达改变。引人注目的是，与其他严重程度组相比，危重型2019冠状病毒病康复患者的CD8 T细胞中CD57表达升高。观察到BCG血清阳性的2019冠状病毒病/脓毒症患者有预后改善的趋势，尽管这可能因组间年龄差异而混淆。相反，单核细胞对刺激的反应似乎不受2019冠状病毒病严重程度的影响。
这些发现突出了感染2019冠状病毒病后患者免疫细胞的长期改变，强调了2019冠状病毒病对免疫功能的重大影响。
