Hoffmann Andrew D, Almubarak Hannah Faisal, Iyer Radhika, Weinberg Sam E, Squires Joshua R, Mao Chengsheng, Wei Juncheng, Chaudhuri Shuvam, El-Shennawy Lamiaa, Dashzeveg Nurmaa K, Jia Yuzhi, Demonbreun Alexis R, Schipma Matthew J, Luo Yuan, Swaminathan Suchitra, Ison Michael G, Liu Huiping, Fang Deyu
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Cell Rep Med. 2025 Aug 19;6(8):102262. doi: 10.1016/j.xcrm.2025.102262. Epub 2025 Jul 31.
Lung transplantation (lung-tx) offers the last life-saving option for patients with COVID-19-associated lung injury (CALI). We show that the RBD-specific antibodies are dramatically reduced in these CALI lung-tx patients despite a comparable frequency of CD19 B cells in circulating blood between CALI lung-tx patients and sero-negative controls. In contrast, non-transplant COVID-19 groups maintain a high level of RBD-specific antibodies. Single-cell RNA sequencing of white blood cells (WBCs) reveals three populations expanded in CALI lung-tx patients, including "lung-tx CD14FCGR3B(CD16b) neutrophils," "lung-tx CD8 T cells," and "KLF2 CD4 T cells," alongside reduced conventional T and B lymphocytes. Elevated expression of interferon (IFN)-responsive genes as part of COVID-19 molecular signatures is sustained in some clusters of monocytes, Tregs, and B cells in all COVID-19 groups. Multiplex analysis of cytokines and chemokines detects a statistically significant increase in interleukin (IL)-6, IL-8, MCP-1, and MIP-1α in circulating blood, specifically in CALI lung-tx patients.
肺移植为新型冠状病毒肺炎相关肺损伤（CALI）患者提供了最后的救命选择。我们发现，尽管CALI肺移植患者与血清阴性对照组循环血液中CD19 B细胞频率相当，但这些CALI肺移植患者中RBD特异性抗体显著减少。相比之下，非移植新型冠状病毒肺炎组维持高水平的RBD特异性抗体。白细胞（WBC）的单细胞RNA测序揭示了CALI肺移植患者中扩增的三个细胞群，包括“肺移植CD14FCGR3B（CD16b）中性粒细胞”、“肺移植CD8 T细胞”和“KLF2 CD4 T细胞”，同时传统T和B淋巴细胞减少。作为新型冠状病毒肺炎分子特征一部分的干扰素（IFN）反应基因的表达升高，在所有新型冠状病毒肺炎组的一些单核细胞、调节性T细胞和B细胞簇中持续存在。细胞因子和趋化因子的多重分析检测到循环血液中白细胞介素（IL）-6、IL-8、单核细胞趋化蛋白-1和巨噬细胞炎性蛋白-1α有统计学显著增加，特别是在CALI肺移植患者中。
