Title: An inflammatory cytokine signature predicts COVID-19 severity and survival
Author: Diane Marie Del Valle, Seunghee Kim-Schulze, Hsin-Hui Huang, Noam D. Beckmann, Sharon Nirenberg, Bo Wang, Yonit Lavin, Talia H. Swartz, Deepu Madduri, Aryeh Stock, Thomas U. Marron, Hui Xie, Manishkumar Patel, Kevin Tuballes, Oliver Van Oekelen, Adeeb Rahman, Patricia Kovatch, Judith A. Aberg, Eric Schadt, Sundar Jagannath, Madhu Mazumdar, Alexander W. Charney, Adolfo Firpo-Betancourt, Damodara Rao Mendu, Jeffrey Jhang, David Reich, Keith Sigel, Carlos Cordon-Cardo, Marc Feldmann, Samir Parekh, Miriam Merad, Sacha Gnjatic
Abstract: 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.