Characterization of fibrosis-associated pathways in human lung tissue samples in COVID-19 and fibrotic lung diseases

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Abstract
Introduction: Pulmonary manifestations of COVID-19 range from asymptomatic cases over severe acute lung injuries such as ARDS to pulmonary long-COVID manifestations. In addition to hyperinflammation, fibrotic lung changes may occur, whose pathogenesis is not yet fully understood. Aims and objectives: The aim of our pilot study was to characterize differences of fibrosis-associated pathways in patients with acute COVID-19 ARDS and long-COVID-ILD compared to non COVID-19 ARDS and other ILD, respectively. Methods: We performed comprehensive transcriptome analyses for RNA sequencing (TruSeq-RNA Kit, Fa. Illumina) on 18 formalin-fixed, paraffin-embedded (FFPE) lung samples (autopsy/intraoperative tissue samples, lung biopsies) from patients with COVID-19 ARDS +/- invasive ventilation and long-COVID-ILD compared to 30 control samples from non COVID-ARDS, NSIP, COP, IPF and healthy lung tissue. Results: In general, transcriptome analyses on FFPE material were challenging due to RNA denaturation. Both homologous and significantly differentially regulated gene expression patterns were identifiable relating to specific fibrosis pathways in COVID-19, non COVID-ARDS, COP and NSIP (see Figure 1). Conclusions: Our preliminary transcriptome analyses suggest distinct gene expression patterns in the various subgroups and may set the basis for future molecular biological studies to understand specific lung fibrosis pathways.