tetano
Editor, Senior Moderator
Cell Rep Med
. 2022 Jun 28;100680.
doi: 10.1016/j.xcrm.2022.100680. Online ahead of print.
Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19
Dorien Feyaerts[SUP] 1 [/SUP], Julien Hédou[SUP] 1 [/SUP], Joshua Gillard[SUP] 2 [/SUP], Han Chen[SUP] 3 [/SUP], Eileen S Tsai[SUP] 1 [/SUP], Laura S Peterson[SUP] 4 [/SUP], Kazuo Ando[SUP] 1 [/SUP], Monali Manohar[SUP] 5 [/SUP], Evan Do[SUP] 5 [/SUP], Gopal K R Dhondalay[SUP] 5 [/SUP], Jessica Fitzpatrick[SUP] 5 [/SUP], Maja Artandi[SUP] 6 [/SUP], Iris Chang[SUP] 5 [/SUP], Theo T Snow[SUP] 5 [/SUP], R Sharon Chinthrajah[SUP] 7 [/SUP], Christopher M Warren[SUP] 5 [/SUP], Richard Wittman[SUP] 6 [/SUP], Justin G Meyerowitz[SUP] 1 [/SUP], Edward A Ganio[SUP] 1 [/SUP], Ina A Stelzer[SUP] 1 [/SUP], Xiaoyuan Han[SUP] 8 [/SUP], Franck Verdonk[SUP] 1 [/SUP], Dyani K Gaudillière[SUP] 9 [/SUP], Nilanjan Mukherjee[SUP] 3 [/SUP], Amy S Tsai[SUP] 1 [/SUP], Kristen K Rumer[SUP] 1 [/SUP], Danielle R Jacobsen[SUP] 1 [/SUP], Zachary B Bjornson-Hooper[SUP] 3 [/SUP], Sizun Jiang[SUP] 3 [/SUP], Sergio Fragoso Saavedra[SUP] 10 [/SUP], Sergio Iván Valdés Ferrer[SUP] 11 [/SUP], J Daniel Kelly[SUP] 12 [/SUP], David Furman[SUP] 13 [/SUP], Nima Aghaeepour[SUP] 14 [/SUP], Martin S Angst[SUP] 1 [/SUP], Scott D Boyd[SUP] 15 [/SUP], Benjamin A Pinsky[SUP] 16 [/SUP], Garry P Nolan[SUP] 17 [/SUP], Kari C Nadeau[SUP] 18 [/SUP], Brice Gaudillière[SUP] 19 [/SUP], David R McIlwain[SUP] 3 [/SUP]
Affiliations
Abstract
The biological determinants underlying the range of coronavirus 2019 (COVID-19) clinical manifestations are not fully understood. Here, over 1,400 plasma proteins and 2,600 single-cell immune features comprising cell phenotype, endogenous signaling activity, and signaling responses to inflammatory ligands are cross-sectionally assessed in peripheral blood from 97 patients with mild, moderate, and severe COVID-19 and 40 uninfected patients. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identify and independently validate a multi-variate model classifying COVID-19 severity (multi-class area under the curve [AUC][SUB]training[/SUB] = 0.799, p = 4.2e-6; multi-class AUC[SUB]validation[/SUB] = 0.773, p = 7.7e-6). Examination of informative model features reveals biological signatures of COVID-19 severity, including the dysregulation of JAK/STAT, MAPK/mTOR, and nuclear factor κB (NF-κB) immune signaling networks in addition to recapitulating known hallmarks of COVID-19. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for prevention and/or treatment of COVID-19 progression.
Keywords: COVID-19; CyTOF; Olink; PBMC; SARS-CoV-2; immunophenotyping; mass cytometry; phosphosignaling response; proteomics; stacked generalization.
. 2022 Jun 28;100680.
doi: 10.1016/j.xcrm.2022.100680. Online ahead of print.
Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19
Dorien Feyaerts[SUP] 1 [/SUP], Julien Hédou[SUP] 1 [/SUP], Joshua Gillard[SUP] 2 [/SUP], Han Chen[SUP] 3 [/SUP], Eileen S Tsai[SUP] 1 [/SUP], Laura S Peterson[SUP] 4 [/SUP], Kazuo Ando[SUP] 1 [/SUP], Monali Manohar[SUP] 5 [/SUP], Evan Do[SUP] 5 [/SUP], Gopal K R Dhondalay[SUP] 5 [/SUP], Jessica Fitzpatrick[SUP] 5 [/SUP], Maja Artandi[SUP] 6 [/SUP], Iris Chang[SUP] 5 [/SUP], Theo T Snow[SUP] 5 [/SUP], R Sharon Chinthrajah[SUP] 7 [/SUP], Christopher M Warren[SUP] 5 [/SUP], Richard Wittman[SUP] 6 [/SUP], Justin G Meyerowitz[SUP] 1 [/SUP], Edward A Ganio[SUP] 1 [/SUP], Ina A Stelzer[SUP] 1 [/SUP], Xiaoyuan Han[SUP] 8 [/SUP], Franck Verdonk[SUP] 1 [/SUP], Dyani K Gaudillière[SUP] 9 [/SUP], Nilanjan Mukherjee[SUP] 3 [/SUP], Amy S Tsai[SUP] 1 [/SUP], Kristen K Rumer[SUP] 1 [/SUP], Danielle R Jacobsen[SUP] 1 [/SUP], Zachary B Bjornson-Hooper[SUP] 3 [/SUP], Sizun Jiang[SUP] 3 [/SUP], Sergio Fragoso Saavedra[SUP] 10 [/SUP], Sergio Iván Valdés Ferrer[SUP] 11 [/SUP], J Daniel Kelly[SUP] 12 [/SUP], David Furman[SUP] 13 [/SUP], Nima Aghaeepour[SUP] 14 [/SUP], Martin S Angst[SUP] 1 [/SUP], Scott D Boyd[SUP] 15 [/SUP], Benjamin A Pinsky[SUP] 16 [/SUP], Garry P Nolan[SUP] 17 [/SUP], Kari C Nadeau[SUP] 18 [/SUP], Brice Gaudillière[SUP] 19 [/SUP], David R McIlwain[SUP] 3 [/SUP]
Affiliations
- PMID: 35839768
- PMCID: PMC9238057
- DOI: 10.1016/j.xcrm.2022.100680
Abstract
The biological determinants underlying the range of coronavirus 2019 (COVID-19) clinical manifestations are not fully understood. Here, over 1,400 plasma proteins and 2,600 single-cell immune features comprising cell phenotype, endogenous signaling activity, and signaling responses to inflammatory ligands are cross-sectionally assessed in peripheral blood from 97 patients with mild, moderate, and severe COVID-19 and 40 uninfected patients. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identify and independently validate a multi-variate model classifying COVID-19 severity (multi-class area under the curve [AUC][SUB]training[/SUB] = 0.799, p = 4.2e-6; multi-class AUC[SUB]validation[/SUB] = 0.773, p = 7.7e-6). Examination of informative model features reveals biological signatures of COVID-19 severity, including the dysregulation of JAK/STAT, MAPK/mTOR, and nuclear factor κB (NF-κB) immune signaling networks in addition to recapitulating known hallmarks of COVID-19. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for prevention and/or treatment of COVID-19 progression.
Keywords: COVID-19; CyTOF; Olink; PBMC; SARS-CoV-2; immunophenotyping; mass cytometry; phosphosignaling response; proteomics; stacked generalization.