Flores-Gonzalez Julio, Buendia-Roldan Ivette, Téllez-Quijada Fernanda, Peña-Bates Carlos, Ramón-Luing Lucero A, Castorena-Maldonado Armando, Falfán-Valencia Ramcés, Pérez-Rubio Gloria, Selman Moisés, Chavez-Galan Leslie, Chávez-Galán Leslie
Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, 14080, Mexico.
Respir Res. 2025 Jan 18;26(1):22. doi: 10.1186/s12931-025-03102-2.
Post-COVID-19 respiratory sequelae often involve lung damage, which is called residual lung abnormalities, and potentially lead to chronic respiratory issues. The adaptive immune response, involving T-cells and B-cells, plays a critical role in pathogen control, inflammation, and tissue repair. However, the link between immune dysregulation and the development of residual lung abnormalities remains unclear.
109 patients discharged with residual lung abnormalities after a critical COVID-19 were followed for 12 months and divided as full recovery patients (FRG, n = 88) and persistent lung abnormalities (PLAG, n = 21). Cell profiling analysis was done using flow cytometry at 24 h of not antigen-specific in vitro stimulation. Plasma or supernatant levels of IFN-g, IL-4, IL-10, IgM, and IgG were assessed, and 10 patients (5 FRG, 5 PLAG) were randomly selected for detailed immune cell phenotyping and functional analysis of peripheral blood mononuclear cells using flow cytometry.
Compared to the FRG group, PLAG exhibited an increase of unswitched (p = 0.0159) and decreased double-negative activated B-cells (p = 0.0317), systemic IL-10 levels were lower, displayed reduced frequency of total B-cells, and impaired spontaneous IgM (p = 0.0357) and IgG (p = 0.0079) release in culture. Regarding T-cells, PLAG patients showed a reduction in effector memory CD4 + cells (p = 0.0159) and an increase in CD4 + TEMRA cells (p = 0.0079) following in vitro stimulation. Notably, the PLAG group also exhibited higher frequencies of central memory CD4 + Th2 (GATA3+) T-cells in response to activation than the FRG group (p = 0.0079).
Patients with residual lung abnormalities 12 months post-critical COVID-19 exhibit impaired B-cell function, increased unswitched B-cells, and higher frequencies of CD4 + TEMRA T-cells following in vitro activation. These immune imbalances may contribute to ongoing lung dysfunction and warrant further investigation as a potential mechanism in residual lung abnormalities. Larger studies are necessary to confirm these findings.
新冠病毒感染后肺部后遗症常涉及肺损伤，即所谓的残留肺异常，并可能导致慢性呼吸问题。涉及T细胞和B细胞的适应性免疫反应在病原体控制、炎症和组织修复中起关键作用。然而，免疫失调与残留肺异常发展之间的联系仍不清楚。
对109例新冠病毒感染重症患者出院后仍有残留肺异常的患者进行了12个月的随访，并分为完全康复患者（FRG，n = 88）和持续存在肺异常患者（PLAG，n = 21）。在非抗原特异性体外刺激24小时后，使用流式细胞术进行细胞谱分析。评估了干扰素-γ、白细胞介素-4、白细胞介素-10、免疫球蛋白M和免疫球蛋白G的血浆或上清液水平，并随机选择10例患者（5例FRG，5例PLAG），使用流式细胞术对外周血单个核细胞进行详细的免疫细胞表型分析和功能分析。
与FRG组相比，PLAG组未转换的B细胞增加（p = 0.0159），双阴性活化B细胞减少（p = 0.0317），全身白细胞介素-10水平较低，总B细胞频率降低，培养中自发免疫球蛋白M（p = 0.0357）和免疫球蛋白G（p = 0.0079）释放受损。关于T细胞，PLAG患者在体外刺激后效应记忆CD4 +细胞减少（p = 0.0159），CD4 + TEMRA细胞增加（p = 0.0079）。值得注意的是，与FRG组相比，PLAG组在激活后中央记忆CD4 + Th2（GATA3 +）T细胞的频率也更高（p = 0.0079）。
新冠病毒感染重症患者12个月后仍有残留肺异常的患者表现出B细胞功能受损、未转换B细胞增加以及体外激活后CD4 + TEMRA T细胞频率更高。这些免疫失衡可能导致持续的肺功能障碍，作为残留肺异常的潜在机制值得进一步研究。需要更大规模的研究来证实这些发现。
