Multi-ethnic Investigation of Risk and Immune Determinants of COVID-19 Outcomes

ObjectivesTo compare risk factors for COVID-19 mortality among hospitalized Hispanic, Non-Hispanic Black, and White patients. DesignRetrospecitve cohort study SettingFive hosptials within a single academic health system Participants3,086 adult patients with self-reported race/ethnicity information presenting to the emergency department and hospitalized with COVID-19 up to April 13, 2020. Main outcome measuresIn-hospital mortality ResultsWhile older age (multivariable OR 1.06, 95% CI 1.05-1.07) and baseline hypoxia (multivariable OR 2.71, 95% CI 2.17-3.36) were associated with increased mortality overall and across all races/ethnicities, Non-Hispanic Black (median age 67, IQR 58-76) and Hispanic (median age 63, IQR 50-74) patients were younger and had different comorbidity profiles compared to Non-Hispanic White patients (median age 73, IQR 62-84; p<0.05 for both comparisons). Among inflammatory markers associated with COVID-19 mortality, there was a significant interaction between the Non-Hispanic Black population and interleukin-1-beta (interaction p-value 0.04). ConclusionsThis analysis of a multi-ethnic cohort highlights the need for inclusion and consideration of diverse popualtions in ongoing COVID-19 trials targeting inflammatory cytokines.

An inflammatory cytokine signature helps predict COVID-19 severity and death.

The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. 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 IL-6, IL-8, TNF-α, and IL-1ß in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. 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. Importantly, when adjusting for disease severity score, 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 propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF-α levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.