Dolna-Michno Justyna, Kopiński Piotr, Przybylski Grzegorz, Wypasek Ewa, Szymańska Magdalena, Wędrowska Ewelina, Mikołajczyk Klaudia, Senderek Tomasz, Gagat Maciej
Department of Molecular Biology, John Paul II Hospital, 31-202 Kraków, Poland.
Department of Physiology and Pathophysiology, Medical College, Andrzej Frycz Modrzewski Krakow University, 31-216 Kraków, Poland.
J Clin Med. 2025 May 12;14(10):3361. doi: 10.3390/jcm14103361.
: It has yet to be determined whether the immunocytological profile of the bronchoalveolar lavage (BAL) in respiratory post-COVID syndrome (PCS) reflects the risk of persistent interstitial lung disease (ILD), including pulmonary fibrosis. In this study, we aimed to assess the prognostic value of the BAL cytoimmunologic profile in PCS-related ILD. : We enrolled 58 non-smoking patients with a history of COVID-19 and new-onset ILD, divided into PCS remission and PCS persistence groups based on clinical data, including repeated computed tomography and pulmonary function tests. We phenotyped BAL major T cell subsets, immune checkpoints (including programmed cell death-1, PD1), and markers of Th1/Th2/Th17 polarization. : The PCS groups compared to the control showed increased total cell, lymphocyte, and neutrophil counts and a high BAL neutrophil:lymphocyte ratio (NLR). PCS persistence compared to the controls presented an increased neutrophil count (26 [17-36] vs. 2.6 [1.9-5.4] 10/mL, median [Q1-Q3], < 0.001) and percentage, BAL NLR (0.77 [0.26-1.63] vs. 0.21 [0.17-0.31], < 0.0001), CD8+PD1+ cell percentage (43.5 [34-60.5] vs. 24.5 [22-44]%, = 0.045), and a decreased CD4:CD8 ratio. A high percentage of CD4+CD196+CD183 cells (relevant to Th17 activity, 6.2 [2.0-9.4] vs. 1.2 [0.7-2.7]%, = 0.02) and increased BAL supernatant elevated IL-8 levels (62.5 [16-243] vs. 10.9 [3.44-32] pg/mL, = 0.002) were found in the PCS persistence vs. control groups. In the total PCS group, predicted values of Vital Capacity (VC) [16-243] and Diffusing Lung Capacity for CO (DLCO) correlated negatively with BAL NLR; VC correlated negatively with BAL CD8+PD1+; and DLCO correlated positively with the CD4:CD8 ratio. : Worse prognosis in PCS is associated with higher BAL NLR, BAL neutrophilia, an elevated percentage of CD8+PD1+ lymphocytes, and a decline in the CD4:CD8 ratio. Th17 cells and IL-8 participate in lung PCS persistence.
新冠后综合征（PCS）患者支气管肺泡灌洗（BAL）的免疫细胞特征是否反映包括肺纤维化在内的持续性间质性肺疾病（ILD）的风险尚未确定。在本研究中，我们旨在评估BAL细胞免疫特征在PCS相关ILD中的预后价值。
我们纳入了58例有新冠病史且新发ILD的非吸烟患者，根据包括重复计算机断层扫描和肺功能测试在内的临床数据分为PCS缓解组和PCS持续组。我们对BAL主要T细胞亚群、免疫检查点（包括程序性细胞死亡蛋白1，PD1）以及Th1/Th2/Th17极化标志物进行了表型分析。
与对照组相比，PCS组的总细胞、淋巴细胞和中性粒细胞计数增加，BAL中性粒细胞与淋巴细胞比值（NLR）升高。与对照组相比，PCS持续组的中性粒细胞计数（26 [17 - 36] 对 2.6 [1.9 - 5.4]×10⁶/mL，中位数 [Q1 - Q3]，P < 0.001）和百分比、BAL NLR（0.77 [0.26 - 1.63] 对 0.21 [0.17 - 0.31]，P < 0.0001）、CD8⁺PD1⁺细胞百分比（43.5 [34 - 60.5]% 对 24.5 [22 - 44]%，P = 0.045）升高以及CD4:CD8比值降低。PCS持续组与对照组相比，发现CD4⁺CD196⁺CD183细胞（与Th17活性相关）的百分比高（6.2 [2.0 - 9.4]% 对 1.2 [0.7 - 2.7]%，P = 0.02）且BAL上清液中IL - 8水平升高（62.5 [16 - 243] 对 10.9 [3.44 - 32] pg/mL，P = 0.002）。在整个PCS组中，肺活量（VC）[16 - 243]和一氧化碳弥散量（DLCO）的预测值与BAL NLR呈负相关；VC与BAL CD8⁺PD1⁺呈负相关；DLCO与CD4:CD8比值呈正相关。
PCS预后较差与较高的BAL NLR、BAL中性粒细胞增多、CD8⁺PD1⁺淋巴细胞百分比升高以及CD4:CD8比值下降有关。Th17细胞和IL - 8参与肺部PCS的持续存在。
