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10.1101/2021.02.10.430499 http://scihub22266oqcxt.onion/10.1101/2021.02.10.430499 33594364!7885916!33594364     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       bioRxiv 2021 ; ä (ä): ä Nephropedia Template TP {{tp|p=33594364|t=2021. Bifurcated monocyte states are predictive of mortality in severe COVID-19 |pdf=|usr=}}{{33594364}} gab.com Text Bifurcated monocyte states are predictive of mortality in severe COVID-19 JO: bioRxiv http://www.kidney.de/pget.php?&tw=1&pmid=33594364 #FOAvip Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection presents with varied clinical manifestations(1), ranging from mild symptoms to acute respiratory distress syndrome (ARDS) with high mortality(2,3). Despite extensive analyses, there remains an urgent need to delineate immune cell states that contribute to mortality in severe COVID-19. We performed high-dimensional cellular and molecular profiling of blood and respiratory samples from critically ill COVID-19 patients to define immune cell genomic states that are predictive of outcome in severe COVID-19 disease. Critically ill patients admitted to the intensive care unit (ICU) manifested increased frequencies of inflammatory monocytes and plasmablasts that were also associated with ARDS not due to COVID-19. Single-cell RNAseq (scRNAseq)-based deconvolution of genomic states of peripheral immune cells revealed distinct gene modules that were associated with COVID-19 outcome. Notably, monocytes exhibited bifurcated genomic states, with expression of a cytokine gene module exemplified by CCL4 (MIP-1beta) associated with survival and an interferon signaling module associated with death. These gene modules were correlated with higher levels of MIP-1beta and CXCL10 levels in plasma, respectively. Monocytes expressing genes reflective of these divergent modules were also detectable in endotracheal aspirates. Machine learning algorithms identified the distinctive monocyte modules as part of a multivariate peripheral immune system state that was predictive of COVID-19 mortality. Follow-up analysis of the monocyte modules on ICU day 5 was consistent with bifurcated states that correlated with distinct inflammatory cytokines. Our data suggests a pivotal role for monocytes and their specific inflammatory genomic states in contributing to mortality in life-threatening COVID-19 disease and may facilitate discovery of new diagnostics and therapeutics. Twit Text FOAVip Bifurcated monocyte states are predictive of mortality in severe COVID-19 ????bioRxiv http://www.kidney.de/pget.php?&tw=1&pmid=33594364 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33594364 #FOAvip English Wikipedia <ref>{{Cite pmid|33594364}}</ref> Bifurcated monocyte states are predictive of mortality in severe COVID-19 #MMPMID33594364 Cillo AR; Somasundaram A; Shan F; Cardello C; Workman CJ; Kitsios GD; Ruffin A; Kunning S; Lampenfeld C; Onkar S; Grebinoski S; Deshmukh G; Methe B; Liu C; Nambulli S; Andrews L; 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 bioRxiv 2021[Feb]; ä (ä): ä PMID33594364show ga Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection presents with varied clinical manifestations(1), ranging from mild symptoms to acute respiratory distress syndrome (ARDS) with high mortality(2,3). Despite extensive analyses, there remains an urgent need to delineate immune cell states that contribute to mortality in severe COVID-19. We performed high-dimensional cellular and molecular profiling of blood and respiratory samples from critically ill COVID-19 patients to define immune cell genomic states that are predictive of outcome in severe COVID-19 disease. Critically ill patients admitted to the intensive care unit (ICU) manifested increased frequencies of inflammatory monocytes and plasmablasts that were also associated with ARDS not due to COVID-19. Single-cell RNAseq (scRNAseq)-based deconvolution of genomic states of peripheral immune cells revealed distinct gene modules that were associated with COVID-19 outcome. Notably, monocytes exhibited bifurcated genomic states, with expression of a cytokine gene module exemplified by CCL4 (MIP-1beta) associated with survival and an interferon signaling module associated with death. These gene modules were correlated with higher levels of MIP-1beta and CXCL10 levels in plasma, respectively. Monocytes expressing genes reflective of these divergent modules were also detectable in endotracheal aspirates. Machine learning algorithms identified the distinctive monocyte modules as part of a multivariate peripheral immune system state that was predictive of COVID-19 mortality. Follow-up analysis of the monocyte modules on ICU day 5 was consistent with bifurcated states that correlated with distinct inflammatory cytokines. Our data suggests a pivotal role for monocytes and their specific inflammatory genomic states in contributing to mortality in life-threatening COVID-19 disease and may facilitate discovery of new diagnostics and therapeutics. äBifurcated monocyte states are predictive of mortality in severe COVID(epmc).pdf DeepDyve Pubget Overpricing