Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury

• DOI: 10.1172/jci.insight.157837
• Publication Date: 2022-12-06T17:02:53Z
• Authors: Amy R. Cross; Carlos E. de Andrea; María Villalba-Es...; Manuel F. Landecho; Lucia Cerundolo; Praveen Weeratunga; Rachel E. Etherin...; Laura Denney; Graham Ogg; Ling-Pei Ho; Ian S.D. Roberts; Joanna Hester; Paul Klenerman; Ignacio Melero; Stephen N. Sansom; Fadi Issa
• Keywords: 2019-20 coronavirus outbreak; Hypersensitivity pneumonitis; Pneumonitis

Severe lung damage resulting from COVID-19 involves complex interactions between diverse populations of immune and stromal cells. In this study, we used a spatial transcriptomics approach to delineate the cells, pathways, genes present across spectrum histopathological in COVID-19-affected tissue. We applied correlation network-based approaches deconvolve gene expression data 46 areas interest covering more than 62,000 cells within well-preserved samples 3 patients. Despite substantial interpatient heterogeneity, discovered evidence for common immune-cell signaling circuit severe tissue that crosstalk cytotoxic lymphocytes pro-inflammatory macrophages. Expression IFNG by was associated with induction chemokines, including CXCL9, CXCL10, CXCL11, which are known promote recruitment CXCR3+ The TNF superfamily members BAFF (TNFSF13B) TRAIL (TNFSF10) were consistently upregulated damage. published single-cell SARS-CoV-2 sets validate our findings additional cohorts patients COVID-19. model immune-mediated pathology may inform future therapeutic strategies.