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People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden #MMPMID34873589
Cillo AR; Somasundaram A; Shan F; Cardello C; Workman CJ; Kitsios GD; Ruffin AT; Kunning S; Lampenfeld C; Onkar S; Grebinoski S; Deshmukh G; Methe B; Liu C; Nambulli S; Andrews LP; Duprex WP; Joglekar AV; Benos PV; Ray P; Ray A; McVerry BJ; Zhang Y; Lee JS; Das J; Singh H; Morris A; Bruno TC; Vignali DAA
Cell Rep Med 2021[Dec]; 2 (12): 100476 PMID34873589show ga
Despite extensive analyses, there remains an urgent need to delineate immune cell states that contribute to mortality in people critically ill with COVID-19. Here, we present high-dimensional profiling of blood and respiratory samples from people with severe COVID-19 to examine the association between cell-linked molecular features and mortality outcomes. Peripheral transcriptional profiles by single-cell RNA sequencing (RNA-seq)-based deconvolution of immune states are associated with COVID-19 mortality. Further, persistently high levels of an interferon signaling module in monocytes over time lead to subsequent concerted upregulation of inflammatory cytokines. SARS-CoV-2-infected myeloid cells in the lower respiratory tract upregulate CXCL10, leading to a higher risk of death. Our analysis suggests a pivotal role for viral-infected myeloid cells and protracted interferon signaling in severe COVID-19.