Cutting-edge technology sheds light on lung pathology in severe cases of COVID-19

Lung tissue damage is unfortunately one of the many known manifestations of severe COVID-19 disease; however, the factor(s) driving the chronic lung disease that often ensues in these patients has remained unclear. Recently, scientists from the lab of Anja Hauser at the DRFZ in close collaboration with colleagues from Charité – Universitätsmedizin Berlin have pinpointed a kind of molecular ‘fingerprint’ occurring during SARS-CoV-2 infection, which could explain what triggers this pathology. These results were published in the journal Nature Communications and have important implications for both COVID-19 and other chronic inflammatory conditions.

Using a combination of spatially resolved imaging techniques, the team pinpointed endothelial dysfunction occurring during SARS-CoV-2 infection as the trigger of tissue remodeling pathways, ultimately leading to lung fibrosis. Consistent with the blood vessels being the point of initialization, fibrotic processes originating in specific areas around blood vessels hosted large numbers of macrophages that interacted with local stromal cells via the pro-fibrotic chemokine CCL18 and its receptor CCR8. This promoted a self-sustained and non-resolving local immune response that extended far beyond active viral infection. Their work also identified activated lung niches as specialized microenvironments hosting aggregated T cells with an ‘exhausted’ phenotype and ectopic lymphoid structures in prolonged COVID-19. Thus, these adventitial niches may act as key orchestrators of chronic immunopathology. In future, the team would like to address the question of whether some of the mechanisms identified here may also play a role in autoimmune diseases leading to pulmonary fibrosis, as for example rheumatoid arthritis, Sjögrens syndrome and systemic sclerosis.