{Reference Type}: Journal Article
{Title}: People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden.
{Author}: 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;
{Journal}: Cell Rep Med
{Volume}: 2
{Issue}: 12
{Year}: 12 2021 21
{Factor}: 16.988
{DOI}: 10.1016/j.xcrm.2021.100476
{Abstract}: 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.