The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing

Minfeng Liao; Yang Liu; Jin Yuan; Yanling Wen; Gang Xu; Juanjuan Zhao; Lin Chen; Jinxiu Li; Xin Wang; Fuxiang Wang; Lei Liu; Shuye Zhang; Zheng Zhang

Previous studies have shown the significantly higher levels of inflammatory cytokines, chemokines and interferon stimulated genes associated with disease severity in SARS, MERS and COVID-19 patients [10, 16] . The increased infiltrating macrophages into the lung are identified in the autopsy and animal models, and are thought to be responsible for fueling the inflammation [17] [18] [19] . Macrophages are well known to contain heterogeneous subsets, including tissue resident and monocyte derived populations, covering a broad spectrum from M1 to M2 like phenotype [20] . However, little is known regarding the macrophage subsets and their molecular features in SARS-CoV-2-infected human lungs. Here, we identified 4 groups of lung macrophages which can be classified by FCN1, SPP1 and FABP4 markers according to recent reports [13] . Group 1 & 2 macrophages are FCN1 + and highly inflammatory. They express higher levels of interferon stimulated genes and multiple chemokines, CCL2, CCL3, CCL5, IL-8, CXCL9, CXCL10 and CXCL11, thus identifying the FCN1 + macrophages as the culprit for the deranged hyper-inflammation. We identified the group 3, SPP1 + macrophages likely represented a repaired but also a pro-fibrotic subset [12] . They may counteract the FCN1 + macrophages to dampen the inflammation. Their roles and associations with patient outcomes should be further investigated. The group 4 macrophages are FABP4 + AMs showing higher PPARγ activity which play important physiological roles in metabolizing lipid surfactant [20] . Here, we found that AMs consisted the principle lung macrophages in both controls and mildly infected patients, but was almost completely lost in severely infected lungs. The loss of AMs likely contributed to the failed lung functions. Together, these data improved our understanding of tissue macrophage heterogeneity in the immunopathogenesis of SARS-CoV-2 infection. All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.