Spatial Mapping of SARS-CoV-2 and H1N1 Influenza Lung Injury Identifies Differential Transcriptional Signatures

Severe SARS-CoV-2 infection often leads to development of acute respiratory distress syndrome (ARDS), with profound patho-histological changes in post-mortem lung tissues. However, there remains poor insight into the specific transcriptome expression within these damaged regions. We utilized a new spatial transcriptomic platform in ARDS lung tissue from patients with SARS-CoV-2, Influenza H1N1, or both viruses and analyzed regions of interest with 1860 genes. We identified robust transcriptional signatures of enhanced extracellular remodeling, alternative macrophage activation, and tissue metaplasia specific to SARS-CoV-2, which has not been identified in prior SARS-CoV-2 transcriptome studies. These gene signatures were expressed and enhanced in alveolar epithelium, vascular tissue, and lung macrophages. Both H1N1 and dual infected transcriptome demonstrated an enriched proinflammatory profile. Our results are the first to uncover new regional transcriptional changes related to tissue damage/remodeling, altered cellular phenotype, and vascular injury active in SARS-CoV-2 and presents unique therapeutic targets for COVID-19 related ARDS.