Insights from Transcriptomics: CD163+ Profibrotic Lung Macrophages in COVID-19.

COVID19 begins with upper airway symptoms but proceeds in a significant proportion of patients to life-threatening infection of the lower respiratory tract, where an exuberant inflammatory response, edema, and adverse parenchymal remodeling impair gas exchange. Respiratory failure is caused initially by flooding of the airspaces with plasma exudate, sloughed epithelium, and inflammatory cells. For many patients with COVID19, this acute phase has been observed to give way to a prolonged course of acute respiratory distress syndrome (ARDS), and a significant proportion of patients go on to develop fibroproliferative remodeling of the lung parenchyma, which lengthens the duration of respiratory impairment and mechanical ventilation. Monocyte-derived macrophages have previously been implicated in the fibrotic phase of lung injury in multiple models. From several recent studies that employed single cell genomic techniques, a profile of the transcriptomic state of COVID19 lung macrophages has emerged. Linkages have been made between these macrophages, which are monocyte-derived and CD163+, and profibrotic macrophages found in other contexts, including animal models of fibrosis and Idiopathic Pulmonary Fibrosis. Here, emerging concepts of macrophage profibrotic function in COVID19 are highlighted, with a focus on gaps in knowledge to be addressed by future research. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).