An inflammatory cytokine signature predicts COVID-19 severity and survival.

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

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.