TY - JOUR
T1 - Cell specific peripheral immune responses predict survival in critical COVID-19 patients
AU - Amrute, Junedh M.
AU - Perry, Alexandra M.
AU - Anand, Gautam
AU - Cruchaga, Carlos
AU - Hock, Karl G.
AU - Farnsworth, Christopher W.
AU - Randolph, Gwendalyn J.
AU - Lavine, Kory J.
AU - Steed, Ashley L.
N1 - Funding Information:
This study utilized samples obtained from the Washington University School of Medicine’s COVID-19 biorepository, which is supported by: the Barnes-Jewish Hospital Foundation; the Siteman Cancer Center grant P30 CA091842 from the National Cancer Institute of the National Institutes of Health; and the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the view of the NIH. We appreciate the following key investigators who developed and maintained this biorepository: Jane O’Halloran, MD, Ph.D; Charles Goss, Ph.D, and Phillip Mudd, MD, Ph.D. J.M.A. is funded by the American Heart Association Predoctoral Fellowship [826325]. C.C. is supported by the National Institutes of Health [RF1AG053303, P30AG066444, and RF1AG044546] and the Chan Zuckerberg Initiative (CZI). G.J.R. received funding from NIH R37 AI049653-20S2 and the BJC Foundation and Institute for Clinical and Translational Sciences grant COVID110. K.J.L. is supported by the National Institutes of Health [R01 HL138466, R01 HL139714, R01 HL151078], Leducq Foundation Network, Burroughs Welcome Fund, Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital, and Foundation of Barnes-Jewish Hospital. A.L.S. received funding for this study from the Washington University Institute of Clinical and Translational Sciences and the Burroughs Wellcome Fund.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - SARS-CoV-2 triggers a complex systemic immune response in circulating blood mononuclear cells. The relationship between immune cell activation of the peripheral compartment and survival in critical COVID-19 remains to be established. Here we use single-cell RNA sequencing and Cellular Indexing of Transcriptomes and Epitomes by sequence mapping to elucidate cell type specific transcriptional signatures that associate with and predict survival in critical COVID-19. Patients who survive infection display activation of antibody processing, early activation response, and cell cycle regulation pathways most prominent within B-, T-, and NK-cell subsets. We further leverage cell specific differential gene expression and machine learning to predict mortality using single cell transcriptomes. We identify interferon signaling and antigen presentation pathways within cDC2 cells, CD14 monocytes, and CD16 monocytes as predictors of mortality with 90% accuracy. Finally, we validate our findings in an independent transcriptomics dataset and provide a framework to elucidate mechanisms that promote survival in critically ill COVID-19 patients. Identifying prognostic indicators among critical COVID-19 patients holds tremendous value in risk stratification and clinical management.
AB - SARS-CoV-2 triggers a complex systemic immune response in circulating blood mononuclear cells. The relationship between immune cell activation of the peripheral compartment and survival in critical COVID-19 remains to be established. Here we use single-cell RNA sequencing and Cellular Indexing of Transcriptomes and Epitomes by sequence mapping to elucidate cell type specific transcriptional signatures that associate with and predict survival in critical COVID-19. Patients who survive infection display activation of antibody processing, early activation response, and cell cycle regulation pathways most prominent within B-, T-, and NK-cell subsets. We further leverage cell specific differential gene expression and machine learning to predict mortality using single cell transcriptomes. We identify interferon signaling and antigen presentation pathways within cDC2 cells, CD14 monocytes, and CD16 monocytes as predictors of mortality with 90% accuracy. Finally, we validate our findings in an independent transcriptomics dataset and provide a framework to elucidate mechanisms that promote survival in critically ill COVID-19 patients. Identifying prognostic indicators among critical COVID-19 patients holds tremendous value in risk stratification and clinical management.
UR - http://www.scopus.com/inward/record.url?scp=85124679919&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-28505-3
DO - 10.1038/s41467-022-28505-3
M3 - Article
C2 - 35169146
AN - SCOPUS:85124679919
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 882
ER -