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An inflammatory cytokine signature predicts COVID-19 severity and survival

Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically... Full description

Journal Title: Nature medicine 2020-10, Vol.26 (10), p.1636-1643
Main Author: Del Valle, Diane Marie
Other Authors: Kim-Schulze, Seunghee , Huang, Hsin-Hui , Beckmann, Noam D , Nirenberg, Sharon , Wang, Bo , Lavin, Yonit , Swartz, Talia H , Madduri, Deepu , Stock, Aryeh , Marron, Thomas U , Xie, Hui , Patel, Manishkumar , Tuballes, Kevin , Van Oekelen, Oliver , Rahman, Adeeb , Kovatch, Patricia , Aberg, Judith A , Schadt, Eric , Jagannath, Sundar , Mazumdar, Madhu , Charney, Alexander W , Firpo-Betancourt, Adolfo , Mendu, Damodara Rao , Jhang, Jeffrey , Reich, David , Sigel, Keith , Cordon-Cardo, Carlos , Feldmann, Marc , Parekh, Samir , Merad, Miriam , Gnjatic, Sacha
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
Link: https://www.ncbi.nlm.nih.gov/pubmed/32839624
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title: An inflammatory cytokine signature predicts COVID-19 severity and survival
format: Article
creator:
  • Del Valle, Diane Marie
  • Kim-Schulze, Seunghee
  • Huang, Hsin-Hui
  • Beckmann, Noam D
  • Nirenberg, Sharon
  • Wang, Bo
  • Lavin, Yonit
  • Swartz, Talia H
  • Madduri, Deepu
  • Stock, Aryeh
  • Marron, Thomas U
  • Xie, Hui
  • Patel, Manishkumar
  • Tuballes, Kevin
  • Van Oekelen, Oliver
  • Rahman, Adeeb
  • Kovatch, Patricia
  • Aberg, Judith A
  • Schadt, Eric
  • Jagannath, Sundar
  • Mazumdar, Madhu
  • Charney, Alexander W
  • Firpo-Betancourt, Adolfo
  • Mendu, Damodara Rao
  • Jhang, Jeffrey
  • Reich, David
  • Sigel, Keith
  • Cordon-Cardo, Carlos
  • Feldmann, Marc
  • Parekh, Samir
  • Merad, Miriam
  • Gnjatic, Sacha
subjects:
  • Aged
  • Betacoronavirus
  • Comorbidity
  • Coronavirus Infections - immunology
  • Coronavirus Infections - mortality
  • Coronavirus Infections - physiopathology
  • Coronavirus Infections - therapy
  • Coronaviruses
  • COVID-19
  • Cytokines
  • Cytokines - immunology
  • Female
  • Health aspects
  • Hospital patients
  • Hospitalization
  • Humans
  • Inflammation
  • Interleukin-1beta - immunology
  • Interleukin-6 - immunology
  • Interleukin-8 - immunology
  • Interleukins
  • Male
  • Medical colleges
  • Medical research
  • Medicine, Experimental
  • Middle Aged
  • Pandemics
  • Physiological aspects
  • Pneumonia, Viral - immunology
  • Pneumonia, Viral - mortality
  • Pneumonia, Viral - physiopathology
  • Pneumonia, Viral - therapy
  • Prognosis
  • SARS-CoV-2
  • Severe acute respiratory syndrome
  • Severity of Illness Index
  • Survival Rate
  • Tumor necrosis factor
  • Tumor Necrosis Factor-alpha - immunology
ispartof: Nature medicine, 2020-10, Vol.26 (10), p.1636-1643
description: Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P 
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
url: Link


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titleAn inflammatory cytokine signature predicts COVID-19 severity and survival
creatorDel Valle, Diane Marie ; Kim-Schulze, Seunghee ; Huang, Hsin-Hui ; Beckmann, Noam D ; Nirenberg, Sharon ; Wang, Bo ; Lavin, Yonit ; Swartz, Talia H ; Madduri, Deepu ; Stock, Aryeh ; Marron, Thomas U ; Xie, Hui ; Patel, Manishkumar ; Tuballes, Kevin ; Van Oekelen, Oliver ; Rahman, Adeeb ; Kovatch, Patricia ; Aberg, Judith A ; Schadt, Eric ; Jagannath, Sundar ; Mazumdar, Madhu ; Charney, Alexander W ; Firpo-Betancourt, Adolfo ; Mendu, Damodara Rao ; Jhang, Jeffrey ; Reich, David ; Sigel, Keith ; Cordon-Cardo, Carlos ; Feldmann, Marc ; Parekh, Samir ; Merad, Miriam ; Gnjatic, Sacha
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descriptionSeveral studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.
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subjectAged ; Betacoronavirus ; Comorbidity ; Coronavirus Infections - immunology ; Coronavirus Infections - mortality ; Coronavirus Infections - physiopathology ; Coronavirus Infections - therapy ; Coronaviruses ; COVID-19 ; Cytokines ; Cytokines - immunology ; Female ; Health aspects ; Hospital patients ; Hospitalization ; Humans ; Inflammation ; Interleukin-1beta - immunology ; Interleukin-6 - immunology ; Interleukin-8 - immunology ; Interleukins ; Male ; Medical colleges ; Medical research ; Medicine, Experimental ; Middle Aged ; Pandemics ; Physiological aspects ; Pneumonia, Viral - immunology ; Pneumonia, Viral - mortality ; Pneumonia, Viral - physiopathology ; Pneumonia, Viral - therapy ; Prognosis ; SARS-CoV-2 ; Severe acute respiratory syndrome ; Severity of Illness Index ; Survival Rate ; Tumor necrosis factor ; Tumor Necrosis Factor-alpha - immunology
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24Jhang, Jeffrey
25Reich, David
26Sigel, Keith
27Cordon-Cardo, Carlos
28Feldmann, Marc
29Parekh, Samir
30Merad, Miriam
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0An inflammatory cytokine signature predicts COVID-19 severity and survival
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descriptionSeveral studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.
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titleAn inflammatory cytokine signature predicts COVID-19 severity and survival
authorDel Valle, Diane Marie ; Kim-Schulze, Seunghee ; Huang, Hsin-Hui ; Beckmann, Noam D ; Nirenberg, Sharon ; Wang, Bo ; Lavin, Yonit ; Swartz, Talia H ; Madduri, Deepu ; Stock, Aryeh ; Marron, Thomas U ; Xie, Hui ; Patel, Manishkumar ; Tuballes, Kevin ; Van Oekelen, Oliver ; Rahman, Adeeb ; Kovatch, Patricia ; Aberg, Judith A ; Schadt, Eric ; Jagannath, Sundar ; Mazumdar, Madhu ; Charney, Alexander W ; Firpo-Betancourt, Adolfo ; Mendu, Damodara Rao ; Jhang, Jeffrey ; Reich, David ; Sigel, Keith ; Cordon-Cardo, Carlos ; Feldmann, Marc ; Parekh, Samir ; Merad, Miriam ; Gnjatic, Sacha
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abstractSeveral studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.
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