People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden

Anthony R. Cillo; Ashwin Somasundaram; Feng Shan; Carly Cardello; Creg J. Workman; Georgios D. Kitsios; Ayana T. Ruffin; Sheryl Kunning; Caleb Lampenfeld; Sayali Onkar; Stephanie Grebinoski; Gaurav Deshmukh; Barbara Methe; Chang Liu; Sham Nambulli; Lawrence P. Andrews; W. Paul Duprex; Alok V. Joglekar; Panayiotis V. Benos; Prabir Ray; Anuradha Ray; Bryan J. McVerry; Yingze Zhang; Janet S. Lee; Jishnu Das; Harinder Singh; Alison Morris; Tullia C. Bruno; Dario A.A. Vignali

doi:10.1016/j.xcrm.2021.100476

People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden

Anthony R. Cillo, Ashwin Somasundaram, Feng Shan, Carly Cardello, Creg J. Workman, Georgios D. Kitsios, Ayana T. Ruffin, Sheryl Kunning, Caleb Lampenfeld, Sayali Onkar, Stephanie Grebinoski, Gaurav Deshmukh, Barbara Methe, Chang Liu, Sham Nambulli, Lawrence P. Andrews, W. Paul Duprex, Alok V. Joglekar, Panayiotis V. Benos, Prabir RayAnuradha Ray, Bryan J. McVerry, Yingze Zhang, Janet S. Lee, Jishnu Das, Harinder Singh, Alison Morris, Tullia C. Bruno, Dario A.A. Vignali

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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.

Original language	English
Article number	100476
Journal	Cell Reports Medicine
Volume	2
Issue number	12
DOIs	https://doi.org/10.1016/j.xcrm.2021.100476
State	Published - Dec 21 2021

Keywords

COVID-19
COVID-19 outcome
gene modules
inflammatory cytokines
inflammatory monocytes
machine learning
severe COVID-19
single-cell RNA-seq
type I interferon

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10.1016/j.xcrm.2021.100476

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Cillo, A. R., Somasundaram, A., Shan, F., Cardello, C., Workman, C. J., Kitsios, G. D., Ruffin, A. T., Kunning, S., Lampenfeld, C., Onkar, S., Grebinoski, S., Deshmukh, G., Methe, B., Liu, C., Nambulli, S., Andrews, L. P., Duprex, W. P., Joglekar, A. V., Benos, P. V., ... Vignali, D. A. A. (2021). People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden. Cell Reports Medicine, 2(12), Article 100476. https://doi.org/10.1016/j.xcrm.2021.100476

@article{21b6e6c5abe74f4e951080146e51e0ef,

title = "People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden",

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.",

keywords = "COVID-19, COVID-19 outcome, gene modules, inflammatory cytokines, inflammatory monocytes, machine learning, severe COVID-19, single-cell RNA-seq, type I interferon",

author = "Cillo, {Anthony R.} and Ashwin Somasundaram and Feng Shan and Carly Cardello and Workman, {Creg J.} and Kitsios, {Georgios D.} and Ruffin, {Ayana T.} and Sheryl Kunning and Caleb Lampenfeld and Sayali Onkar and Stephanie Grebinoski and Gaurav Deshmukh and Barbara Methe and Chang Liu and Sham Nambulli and Andrews, {Lawrence P.} and Duprex, {W. Paul} and Joglekar, {Alok V.} and Benos, {Panayiotis V.} and Prabir Ray and Anuradha Ray and McVerry, {Bryan J.} and Yingze Zhang and Lee, {Janet S.} and Jishnu Das and Harinder Singh and Alison Morris and Bruno, {Tullia C.} and Vignali, {Dario A.A.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = dec,

day = "21",

doi = "10.1016/j.xcrm.2021.100476",

language = "English",

volume = "2",

journal = "Cell Reports Medicine",

issn = "2666-3791",

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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 2021, 'People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden', Cell Reports Medicine, vol. 2, no. 12, 100476. https://doi.org/10.1016/j.xcrm.2021.100476

TY - JOUR

T1 - People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden

AU - Cillo, Anthony R.

AU - Somasundaram, Ashwin

AU - Shan, Feng

AU - Cardello, Carly

AU - Workman, Creg J.

AU - Kitsios, Georgios D.

AU - Ruffin, Ayana T.

AU - Kunning, Sheryl

AU - Lampenfeld, Caleb

AU - Onkar, Sayali

AU - Grebinoski, Stephanie

AU - Deshmukh, Gaurav

AU - Methe, Barbara

AU - Liu, Chang

AU - Nambulli, Sham

AU - Andrews, Lawrence P.

AU - Duprex, W. Paul

AU - Joglekar, Alok V.

AU - Benos, Panayiotis V.

AU - Ray, Prabir

AU - Ray, Anuradha

AU - McVerry, Bryan J.

AU - Zhang, Yingze

AU - Lee, Janet S.

AU - Das, Jishnu

AU - Singh, Harinder

AU - Morris, Alison

AU - Bruno, Tullia C.

AU - Vignali, Dario A.A.

PY - 2021/12/21

Y1 - 2021/12/21

N2 - 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.

AB - 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.

KW - COVID-19

KW - COVID-19 outcome

KW - gene modules

KW - inflammatory cytokines

KW - inflammatory monocytes

KW - machine learning

KW - severe COVID-19

KW - single-cell RNA-seq

KW - type I interferon

UR - http://www.scopus.com/inward/record.url?scp=85121125509&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2021.100476

DO - 10.1016/j.xcrm.2021.100476

M3 - Article

C2 - 34873589

AN - SCOPUS:85121125509

SN - 2666-3791

VL - 2

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 12

M1 - 100476

ER -

People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden

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