Summary Severe SARS-CoV-2 infection often leads to the development of acute respiratory distress syndrome (ARDS), with profound pulmonary patho-histological changes post-mortem. It is not clear whether ARDS from SARS-CoV-2 is similar to that observed in influenza H1N1, another common viral cause of lung injury. Here, we analyze specific ARDS regions of interest utilizing a spatial transcriptomic platform on autopsy-derived lung tissue from patients with SARS-CoV-2 (n = 3), H1N1 (n = 3), and a dual infected individual (n = 1). Enhanced gene signatures in alveolar epithelium, vascular tissue, and lung macrophages identify not only increased regional coagulopathy but also increased extracellular remodeling, alternative macrophage activation, and squamous metaplasia of type II pneumocytes in SARS-CoV-2. Both the H1N1 and dual-infected transcriptome demonstrated an enhanced antiviral response compared to SARS-CoV-2. Our results uncover regional transcriptional changes related to tissue damage/remodeling, altered cellular phenotype, and vascular injury active in SARS-CoV-2 and present therapeutic targets for COVID-19-related ARDS. Graphical abstract Highlights SARS-CoV-2 and H1N1-induced ARDS show unique transcriptional signatures Tissue remodeling pathways dominate the transcriptional profile of SARS-CoV-2 ARDS SARS-CoV-2/H1N1 double infection resembles the lung anti-viral response to H1N1 Lung injury can be induced by viral infections, such as H1N1 and SARS-CoV-2 infections. Here, Margaroli et al. investigate differential lung responses to both viruses. SARS-CoV-2-induced genes relate to tissue remodeling, while the H1N1 profile is skewed toward anti-viral responses.
【저자키워드】 COVID-19, SARS-CoV-2, ARDS, spatial transcriptomics, H1N1 influenza, 【초록키워드】 Transcriptome, Macrophage, ARDS, macrophages, acute respiratory distress syndrome, Influenza, SARS-COV-2 infection, lung, Lung injury, viral infections, Autopsy, Type II pneumocyte, Coagulopathy, Region, Viral, response, pathway, phenotype, H1N1, Post-mortem, tissue remodeling, change, SARS-CoV-2 infections, platform, macrophage activation, therapeutic targets, acute respiratory distress, cellular, antiviral response, Injury, therapeutic target, leads, dual, respiratory distress, double infection, squamous metaplasia, Vascular injury, Abstract, tissue, SARS-CoV-2 ARDS, infected individual, syndrome, both viruses, severe SARS, lung tissue, anti-viral response, type II pneumocytes, remodeling, gene signature, anti-viral responses, alveolar epithelium, induced genes, vascular tissue, enhanced, transcriptomic, transcriptional, Extracellular, identify, unique, demonstrated, transcriptional change, patients with SARS-CoV-2, skewed, 【제목키워드】 Lung injury, transcriptional, identify,