Monocyte-derived alveolar macrophages drive lung injury and fibrosis in murine models and are associated with pulmonary fibrosis in humans. Monocyte-derived alveolar macrophages have been suggested to develop a phenotype that promotes lung repair as injury resolves. We compared single-cell and cytokine profiling of the alveolar space in a cohort of 35 patients with post-acute sequelae of COVID-19 who had persistent respiratory symptoms and abnormalities on a computed tomography scan of the chest that subsequently improved or progressed. The abundance of monocyte-derived alveolar macrophages, their gene expression programs, and the level of the monocyte chemokine CCL2 in bronchoalveolar lavage fluid positively associated with the severity of radiographic fibrosis. Monocyte-derived alveolar macrophages from patients with resolving or progressive fibrosis expressed the same set of profibrotic genes. Our findings argue against a distinct reparative phenotype in monocyte-derived alveolar macrophages, highlighting their utility as a biomarker of failed lung repair and a potential target for therapy.

单核细胞衍生的肺泡巨噬细胞在小鼠模型中驱动肺损伤和纤维化，并与人类肺纤维化有关。单核细胞衍生的肺泡巨噬细胞被认为会随着损伤的消退而形成一种促进肺修复的表型。我们比较了一组 35 名 COVID-19 急性后遗症患者的肺泡腔单细胞和细胞因子分析，这些患者在胸部计算机断层扫描中出现持续的呼吸道症状和异常，随后有所改善或进展。支气管肺泡灌洗液中单核细胞衍生的肺泡巨噬细胞的丰度、它们的基因表达程序和单核细胞趋化因子 CCL2 的水平与影像学纤维化的严重程度呈正相关。来自已消退或进行性纤维化患者的单核细胞衍生的肺泡巨噬细胞表达相同的促纤维化基因集。我们的研究结果反对单核细胞衍生的肺泡巨噬细胞中独特的修复表型，强调了它们作为肺修复失败的生物标志物和潜在治疗靶点的效用。