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

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.