IL-8 is a potent pro-inflammatory cytokine playing a key role in the recruitment and activation of neutrophils during inflammation 18, and, given the frequent neutrophilia observed in patients infected with SARS-CoV2, it is possible that IL-8 contributes to COVID-19 pathophysiology. IL-1 is also a highly active pro-inflammatory cytokine, and monotherapy blocking IL-1 activity is used to treat inflammatory diseases, including rheumatoid arthritis and inherited auto-inflammatory syndromes, such as cryopyrin-associated syndromes, and has led to sustained reduction in disease severity 17. TNF-α blockade has been used to treat more than ten different autoimmune inflammatory diseases, suggesting that this might be a potential therapeutic approach to reduce organ damage in patients with COVID-19 (ref. TNF-α is important in nearly all acute inflammatory reactions, acting as an amplifier of inflammation. Beyond IL-6, several cytokines have been shown to be elevated in CRS and to contribute to tissue damage. Several single-center studies have used IL-6 inhibitors to treat patients with COVID-19 with some clinical benefits 15 and reported failures 14. Tocilizumab, an IL-6 receptor inhibitor, is a US Food and Drug Administration (FDA)-approved treatment for CRS in patients receiving CAR T cells 14. Pathogenic inflammation, also referred to as cytokine storm, shares similarities with what was previously seen in patients infected with other severe coronaviruses, including SARS-CoV and Middle East respiratory syndrome coronavirus 12, and bears similarities to cytokine release syndrome (CRS) observed in patients with cancer treated with chimeric antigen receptor-modified (CAR) T cells 13. Consistent with this hypothesis, high levels of inflammatory markers, including C-reactive protein (CRP), ferritin and D-dimer, high neutrophil-to-lymphocyte ratio 6, 7, 8, 9 and increased levels of inflammatory cytokines and chemokines 6, 8, 9, 10, 11 have been observed in patients with severe diseases. Recent studies have suggested that, in addition to direct viral damage, uncontrolled inflammation contributes to disease severity in COVID-19 (refs. There are currently no curative or preventive therapies for COVID-19, highlighting the need to enhance current understanding of SARS-CoV-2 pathogenesis for the rational development of therapeutics. These findings are aligned with outcomes observed in the Mount Sinai Health System 2, 3. A recent study of hospitals in New York City, at the initial epicenter of the COVID-19 pandemic in the United States, reported that, during March 2020, 21% of patients hospitalized with confirmed COVID-19 died 1. 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.Īs of late July 2020, COVID-19 disease, caused by SARS-CoV-2 infection, has resulted in more than 15.5 million infections and 634,000 deaths worldwide. These findings were validated in a second cohort of patients ( n = 231). 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. 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). 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 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. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. 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. Nature Medicine volume 26, pages 1636–1643 ( 2020) Cite this article An inflammatory cytokine signature predicts COVID-19 severity and survival
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