TY - JOUR
T1 - An inflammatory cytokine signature predicts COVID-19 severity and survival
AU - Del Valle, Diane Marie
AU - Kim-Schulze, Seunghee
AU - Huang, Hsin Hui
AU - Beckmann, Noam D.
AU - Nirenberg, Sharon
AU - Wang, Bo
AU - Lavin, Yonit
AU - Swartz, Talia H.
AU - Madduri, Deepu
AU - Stock, Aryeh
AU - Marron, Thomas U.
AU - Xie, Hui
AU - Patel, Manishkumar
AU - Tuballes, Kevin
AU - Van Oekelen, Oliver
AU - Rahman, Adeeb
AU - Kovatch, Patricia
AU - Aberg, Judith A.
AU - Schadt, Eric
AU - Jagannath, Sundar
AU - Mazumdar, Madhu
AU - Charney, Alexander W.
AU - Firpo-Betancourt, Adolfo
AU - Mendu, Damodara Rao
AU - Jhang, Jeffrey
AU - Reich, David
AU - Sigel, Keith
AU - Cordon-Cardo, Carlos
AU - Feldmann, Marc
AU - Parekh, Samir
AU - Merad, Miriam
AU - Gnjatic, Sacha
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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 < 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.
AB - 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 < 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.
UR - http://www.scopus.com/inward/record.url?scp=85089784099&partnerID=8YFLogxK
U2 - 10.1038/s41591-020-1051-9
DO - 10.1038/s41591-020-1051-9
M3 - Article
C2 - 32839624
AN - SCOPUS:85089784099
SN - 1078-8956
VL - 26
SP - 1636
EP - 1643
JO - Nature Medicine
JF - Nature Medicine
IS - 10
ER -