Science Translational Medicine
February 18, 2022
A Window into Lung Injury in COVID-19
In new work, D’Agnillo et al. perform a systems biology analysis of lung autopsy samples from 18 patients with fatal COVID-19. They report that damage to the cells lining lung branches and blood vessel injury together with defective lung tissue repair after SARS-CoV-2 infection resulted in a fatal outcome. These findings further define the molecular features underlying the lung’s response to SARS-CoV-2 infection and indicate stages of disease progression that may help to guide development of therapies to treat patients with severe COVID-19.
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by respiratory distress, multiorgan dysfunction, and, in some cases, death. The pathological mechanisms underlying COVID-19 respiratory distress and the interplay with aggravating risk factors have not been fully defined. Lung autopsy samples from 18 patients with fatal COVID-19, with symptom onset-to-death times ranging from 3 to 47 days, and antemortem plasma samples from 6 of these cases were evaluated using deep sequencing of SARS-CoV-2 RNA, multiplex plasma protein measurements, and pulmonary gene expression and imaging analyses. Prominent histopathological features in this case series included progressive diffuse alveolar damage with excessive thrombosis and late-onset pulmonary tissue and vascular remodeling. Acute damage at the alveolar-capillary barrier was characterized by the loss of surfactant protein expression with injury to alveolar epithelial cells, endothelial cells, respiratory epithelial basal cells, and defective tissue repair processes. Other key findings included impaired clot fibrinolysis with increased concentrations of plasma and lung plasminogen activator inhibitor-1 and modulation of cellular senescence markers, including p21 and sirtuin-1, in both lung epithelial and endothelial cells. Together, these findings further define the molecular pathological features underlying the pulmonary response to SARS-CoV-2 infection and provide important insights into signaling pathways that may be amenable to therapeutic intervention.
In this work, the analytical module of Genedata Profiler, Analyst, was used to perform statistical analysis and visualization of microarray gene expression data.