Journal Article

Profibrotic monocyte-derived alveolar macrophages are expanded in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19

Grant, Rogan A., Jain, Manu, Kurihara, Chitaru, Shilatifard, Ali, Cumming, R. Ian, Sala, Marc A., Puritz, Connor H., Swaminathan, Suchitra, Bharat, Ankit, Jonasson, Emmy, Ludwig, Amy, Ridge, Karen M., Tighe, Robert M., Miller, Janet, San Jose Estepar, Raul, Braun, Rosemary, Washko, George R., San Jose Estepar, Ruben, Mylvaganam, Ruben J., Abdala-Valencia, Hiam, Sznajder, Jacob I., Budinger, G. R. Scott, Markov, Nikolay S., Fenske, Samuel, Yu, Zhan, Gowdy, Kymberly M., Kalhan, Ravi, Diaz, Estefani, Lu, Ziyan, Senkow, Karolina J., Bailey, Joseph I., Misharin, Alexander V.

2024

Overview

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. Misharin, Sala and colleagues show that in patients with lung fibrosis after COVID-19, monocyte-derived alveolar macrophages activate an inflammatory and fibrotic program that was similar in patients with either resolving or progressing fibrosis.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/262 / 692/420/256/2515 / 692/699/255/2514 / Adult / Aged / Alveoli / Animal models / Biomedical and Life Sciences / Biomedicine / Bronchoalveolar Lavage Fluid - cytology / Bronchus / Chemokine CCL2 - metabolism / Chemokines / Complications / Computed tomography / COVID-19 / COVID-19 - immunology / Cytokines - metabolism / Female / Fibrosis / Gene expression / Humans / Immunology / Infectious Diseases / Lavage / Long COVID / Lung - diagnostic imaging / Lung - immunology / Lung - pathology / Lung diseases / Macrophages / Macrophages, Alveolar - immunology / Macrophages, Alveolar - metabolism / Male / Middle Aged / Monocyte chemoattractant protein 1 / Monocytes / Monocytes - immunology / Monocytes - metabolism / Phenotypes / Pulmonary Fibrosis - diagnostic imaging / Pulmonary Fibrosis - etiology / Pulmonary Fibrosis - immunology / SARS-CoV-2 - physiology / Tomography, X-Ray Computed