A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling Article Swipe

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Jason A. Hackney , Haridha Shivram , Jason A. Vander Heiden , Christopher C. Overall , Luz D. Orozco , Xia Gao , Eugene S. Kim , Nathaniel R. West , Aditi Qamra , Diana Chang , Arindam Chakrabarti , David F. Choy , Alexis J. Combes , Tristan Courau , Gabriela K. Fragiadakis , Arjun A. Rao , Arja Ray , Jessica Tsui , Kenneth H. Hu , Nicholas F. Kuhn , Matthew F. Krummel , David J. Erle , Kirsten N. Kangelaris , Aartik Sarma , Zoe M. Lyon , Carolyn S. Calfee , Prescott G. Woodruff , Rajani Ghale , Eran Mick , Ashley Byrne , Beth Shoshana Zha , Charles Langelier , Carolyn M. Hendrickson , Monique G.P. van der Wijst , George C. Hartoularos , Tianna Grant , Raymund Bueno , David Lee , John R. Greenland , Yang Sun , Richard K. Perez , Anton Ogorodnikov , Alyssa Ward , Chun Ye , Yumiko Abe‐Jones , Michael Adkisson , K. Mark Ansel , Saurabh Asthana , Alexander J. Beagle , Sharvari Bhide , Cathy Cai , Saharai Caldera , Lorena Espinar , Sidney Carrillo , Suzanna Chak , Stephanie A. Christenson , Zachary Collins , Spyros Darmanis , Angela M. Detweiler , Catherine DeVoe , Walter L. Eckalbar , Jeremy Giberson , Ana Gonzalez , Gracie Gordon , Paula Hayakawa Serpa , Alejandra Jáuregui , Chayse Jones , Serena Ke , Divya Kushnoor , Tasha Lea , Deanna Lee , Aleksandra Leligdowicz , Yale Liu , Salman Mahboob , Lenka Maliskova , Michael A. Matthay , Elizabeth W. McCarthy , Priscila Muñoz-Sandoval , Norma Neff , Nguyễn Hoàng Việt , Nishita Nigam , Randy Parada , Maíra Phelps , Logan Pierce , Priya A. Prasad , Sadeed Rashid , Gabriella C. Reeder , Nicklaus Rodriguez , Bushra Samad , Andrew Schroeder , Cole Shaw , Alan Shen , Austin Sigman , Pratik Sinha , Matthew H. Spitzer , Sara Sunshine , Kevin Tang , Luz Torres Altamirano , Alexandra Tsitsiklis , Erden Tumurbaatar ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1016/j.isci.2023.107813

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGE^hi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. IL-6 signaling blockade by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of EN-RAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

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Infectious Diseases (Medical Specialty)

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Blockade Coronavirus disease 2019 (COVID-19) 2019-20 coronavirus outbreak Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Myeloid cells Medicine Pandemic Immunology Myeloid Virology Internal medicine Receptor Outbreak Disease Infectious disease (medical specialty)

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Type: article
Language: en
Landing Page: https://doi.org/10.1016/j.isci.2023.107813
PDF: https://doi.org/10.1016/j.isci.2023.107813
OA Status: gold
Cited By: 9
References: 93
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DOI: https://doi.org/10.1016/j.isci.2023.107813

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Title: A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling

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Language: en

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Publication year: 2023

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Publication date: 2023-09-01

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Authors: Jason A. Hackney, Haridha Shivram, Jason A. Vander Heiden, Christopher C. Overall, Luz D. Orozco, Xia Gao, Eugene S. Kim, Nathaniel R. West, Aditi Qamra, Diana Chang, Arindam Chakrabarti, David F. Choy, Alexis J. Combes, Tristan Courau, Gabriela K. Fragiadakis, Arjun A. Rao, Arja Ray, Jessica Tsui, Kenneth H. Hu, Nicholas F. Kuhn, Matthew F. Krummel, David J. Erle, Kirsten N. Kangelaris, Aartik Sarma, Zoe M. Lyon, Carolyn S. Calfee, Prescott G. Woodruff, Rajani Ghale, Eran Mick, Ashley Byrne, Beth Shoshana Zha, Charles Langelier, Carolyn M. Hendrickson, Monique G.P. van der Wijst, George C. Hartoularos, Tianna Grant, Raymund Bueno, David Lee, John R. Greenland, Yang Sun, Richard K. Perez, Anton Ogorodnikov, Alyssa Ward, Chun Ye, Yumiko Abe‐Jones, Michael Adkisson, K. Mark Ansel, Saurabh Asthana, Alexander J. Beagle, Sharvari Bhide, Cathy Cai, Saharai Caldera, Lorena Espinar, Sidney Carrillo, Suzanna Chak, Stephanie A. Christenson, Zachary Collins, Spyros Darmanis, Angela M. Detweiler, Catherine DeVoe, Walter L. Eckalbar, Jeremy Giberson, Ana Gonzalez, Gracie Gordon, Paula Hayakawa Serpa, Alejandra Jáuregui, Chayse Jones, Serena Ke, Divya Kushnoor, Tasha Lea, Deanna Lee, Aleksandra Leligdowicz, Yale Liu, Salman Mahboob, Lenka Maliskova, Michael A. Matthay, Elizabeth W. McCarthy, Priscila Muñoz-Sandoval, Norma Neff, Nguyễn Hoàng Việt, Nishita Nigam, Randy Parada, Maíra Phelps, Logan Pierce, Priya A. Prasad, Sadeed Rashid, Gabriella C. Reeder, Nicklaus Rodriguez, Bushra Samad, Andrew Schroeder, Cole Shaw, Alan Shen, Austin Sigman, Pratik Sinha, Matthew H. Spitzer, Sara Sunshine, Kevin Tang, Luz Torres Altamirano, Alexandra Tsitsiklis, Erden Tumurbaatar

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Concepts: Blockade, Coronavirus disease 2019 (COVID-19), 2019-20 coronavirus outbreak, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Myeloid cells, Medicine, Pandemic, Immunology, Myeloid, Virology, Internal medicine, Receptor, Outbreak, Disease, Infectious disease (medical specialty)

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Cited by: 9

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