IL-6–based mortality risk model for hospitalized patients with COVID-19

Abstract

Background: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic. Because the severity of the disease is highly variable, predictive models to stratify patients according to their mortality risk are needed. Objective: Our aim was to develop a model able to predict the risk of fatal outcome in patients with COVID-19 that could be used easily at the time of patients' arrival at the hospital. Methods: We constructed a prospective cohort with 611 adult patients in whom COVID-19 was diagnosed between March 10 and April 12, 2020, in a tertiary hospital in Madrid, Spain. The analysis included 501 patients who had been discharged or had died by April 20, 2020. The capacity of several biomarkers, measured at the beginning of hospitalization, to predict mortality was assessed individually. Those biomarkers that independently contributed to improve mortality prediction were included in a multivariable risk model. Results: High IL-6 level, C-reactive protein level, lactate dehydrogenase (LDH) level, ferritin level, D-dimer level, neutrophil count, and neutrophil-to-lymphocyte ratio were all predictive of mortality (area under the curve >0.70), as were low albumin level, lymphocyte count, monocyte count, and ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO 2 /FiO 2). A multivariable mortality risk model including the SpO 2 /FiO 2 ratio, neutrophil-to-lymphocyte ratio, LDH level, IL-6 level, and age was developed and showed high accuracy for the prediction of fatal outcome (area under the curve 0.94). The optimal cutoff reliably classified patients (including patients with no initial respiratory distress) as survivors and nonsurvivors with 0.88 sensitivity and 0.89 specificity. Conclusion: This mortality risk model allows early risk stratification of hospitalized patients with COVID-19 before the appearance of obvious signs of clinical deterioration, and it can be used as a tool to guide clinical decision making. (J Allergy Clin Immunol 2020;146:799-807.)

Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients

“…Through comparing the cytokine levels in the serum samples of COVID-19 patients at longitudinal timepoints during severe illness or at recovery, we have identified differential cytokine profiles potentially associated with COVID-19 disease status. Besides IL-6, which has been reported as a potential biomarker for COVID-19 patients ( 28 , 40 ), we found that both IL-6 and IL-8 serum levels were elevated in COVID-19 patients with severe diseases. In particular, we found that serum levels of IL-6 and IL-8 were significantly higher in COVID-19 patients as compared with heath donors with the AUC, which represents the combination of detecting sensitivity and specificity, at 0.84 and 0.98, respectively.…”

An immune-based biomarker signature is associated with mortality in COVID-19 patients

“…To characterize the immunologic response in SARS-CoV-2 infection manifesting with different grades of severity, we measured the concentration of 66 biomarkers associated with monocyte/macrophage, inflammasome, NF-κB, and neutrophil activation; T cell activation and/or polarization; type I IFN and IFN response gene induction; endothelial integrity; and sepsis severity in the peripheral blood of COVID-19 patients and compared them with levels in healthy American volunteers (HVs). Cytokine and chemokine levels can vary considerably in their longitudinal trajectories during the course of COVID-19 as a function of the phase of the disease and receipt of immunomodulatory medications ( 15 , 25 ). Therefore, we focused our initial analysis on 119 patients who underwent the first blood sampling within the initial 7 days of hospitalization ( Supplemental Table 1 and Supplemental Figure 3 ).…”

Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial

“… 11 In covid-19, an increased level of interleukin 6 and C reactive protein correlates with disease severity and mortality. 12 13 Thus, blocking interleukin 6 activity might play a role in mitigating the inflammatory response and improve clinical outcomes in patients with covid-19. To test this hypothesis, we conducted a randomised controlled trial comparing tocilizumab plus standard care with standard care alone in patients admitted to hospital with severe or critical covid-19.…”