Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.05.238360v1?rss=1 Authors: Zhang, F., Mears, J. R., Shakib, L., Beynor, J. I., Shanaj, S., Korsunsky, I., Nathan, A., Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus,, Donlin, L. T., Raychaudhuri, S. Abstract: Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies. Using an integrative strategy, we built a reference by meta-analyzing > 300,000 immune cells from COVID-19 and 5 inflammatory diseases including rheumatoid arthritis (RA), Crohn disease (CD), ulcerative colitis (UC), lupus, and interstitial lung disease. Our cross-disease analysis revealed that an FCN1+ inflammatory macrophage state is common to COVID-19 bronchoalveolar lavage samples, RA synovium, CD ileum, and UC colon. We also observed that a CXCL10+ CCL2+ inflammatory macrophage state is abundant in severe COVID-19, inflamed CD and RA, and expresses inflammatory genes such as GBP1, STAT1, and IL1B. We found that the CXCL10+ CCL2+ macrophages are transcriptionally similar to blood-derived macrophages stimulated with TNF- and IFN-{gamma} ex vivo. Our findings suggest that IFN-{gamma}, alongside TNF-, might be a key driver of this abundant inflammatory macrophage phenotype in severe COVID-19 and other inflammatory diseases, which may be targeted by existing immunomodulatory therapies. Copy rights belong to original authors. Visit the link for more info