ABSTRACT
Background: In COVID-19 survivors, there is an increased prevalence of pulmonary fibrosis of which the underlying molecular mechanisms are poorly understood. Aims and objectives: In this study, we aimed to gain insights into the evolution of pulmonary fibrogenesis in COVID19. Method(s): In this multicentric study, n=12 patients who succumbed to COVID-19 due to progressive respiratory failure were assigned to an early and late group (death within <=7 and >7 days of hospitalization, respectively) and compared to n=11 healthy controls;mRNA and protein expression were analyzed using a fibrosis-specific panel and immunostaining. Biological pathway analysis was performed using two different gene expression databases. Result(s): Median duration of hospitalization until death was 3 (IQR25-75, 3-3.75) and 14 (12.5-14) days in the early and late group, respectively. Fifty-eight out of 770 analyzed genes showed a significantly altered expression signature in COVID-19 compared to controls in a time-dependent manner. The entire study group showed an increased expression of Bone Marrow Stromal Cell Antigen 2 (BST2) and interleukin-1 receptor 1 (IL1R1), independent of hospitalization time. In the early group, there was increased activity of inflammation-related genes and pathways, while fibrosis-related genes (particularly PDGFRB) and pathways dominated in the late group. Conclusion(s): After the first week of hospitalization, there is a shift from pro-inflammatory to fibrogenic activity in severe COVID-19. IL1R1 and PDGFRB may serve as potential therapeutic targets in future studies.