An inflammatory cytokine signature predicts COVID-19 severity and survival

• Published in: Nature medicine Vol. 26; no. 10; pp. 1636 - 1643
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2020; Nature Publishing Group
• Subjects: 631/250/127/1213; 631/250/127/1220; 631/326/2521; 692/308/409; 692/308/53; Aged; Betacoronavirus; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer Research; Clinical trials; Comorbidity; Coronavirus Infections - immunology; Coronavirus Infections - mortality; Coronavirus Infections - physiopathology; Coronavirus Infections - therapy; Coronaviruses; COVID-19; Cytokines; Cytokines - immunology; Female; Hospitalization; Humans; Hypoxia; Infectious Diseases; Inflammation; Inflammatory response; Interleukin 6; Interleukin 8; Interleukin-1beta - immunology; Interleukin-6 - immunology; Interleukin-8 - immunology; Laboratories; Laboratory tests; Male; Metabolic Diseases; Middle Aged; Molecular Medicine; Neurosciences; Pandemics; Patients; Physiological aspects; Pneumonia, Viral - immunology; Pneumonia, Viral - mortality; Pneumonia, Viral - physiopathology; Pneumonia, Viral - therapy; Resource allocation; Respiratory diseases; SARS-CoV-2; Serum levels; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Survival; Survival Rate; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Viral diseases; United States
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-020-1051-9

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. Elevated levels of serum IL-6 and TNF-α at the time of hospitalization are independent and significant predictors of clinical outcome in two cohorts of patients with COVID-19.