Identification of immune signatures associated with both SARS-CoV-2 infection and lung transplantation

识别与SARS-CoV-2感染和肺移植相关的免疫特征

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作者:Andrew D Hoffmann ,Hannah Faisal Almubarak ,Radhika Iyer ,Sam E Weinberg ,Joshua R Squires ,Chengsheng Mao ,Juncheng Wei ,Shuvam Chaudhuri ,Lamiaa El-Shennawy ,Nurmaa K Dashzeveg ,Yuzhi Jia ,Alexis R Demonbreun ,Matthew J Schipma ,Yuan Luo ,Suchitra Swaminathan ,Michael G Ison ,Huiping Liu ,Deyu Fang

Abstract

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 CD14+FCGR3B(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.

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