Background: We present data on risk factors for severe outcomes among patients with coronavirus disease 2019 (COVID-19) in the southeast United States (U.S.). Objective: To determine risk factors associated with hospitalization, intensive care unit (ICU) admission, and mortality among patients with confirmed COVID-19. Design: A retrospective cohort study. Setting: Fulton County in Atlanta Metropolitan Area, Georgia, U.S. Patients: Community-based individuals of all ages that tested positive for SARS-CoV-2. Measurements: Demographic characteristics, comorbid conditions, hospitalization, ICU admission, death (all-cause mortality), and severe COVID-19 disease, defined as a composite measure of hospitalization and death. Results: Between March 2 and May 31, 2020, we included 4322 individuals with various COVID-19 outcomes. In a multivariable logistic regression random-effects model, patients in age groups ≥45 years compared to those <25 years were associated with severe COVID-19. Males compared to females (adjusted odds ratio [aOR] 1.4, 95% confidence interval [CI]: 1.1-1.6), non-Hispanic blacks (aOR 1.9, 95%CI: 1.5-2.4) and Hispanics (aOR 1.7, 95%CI: 1.2-2.5) compared to non-Hispanic whites were associated with increased odds of severe COVID-19. Those with chronic renal disease (aOR 3.6, 95%CI: 2.2-5.8), neurologic disease (aOR 2.8, 95%CI: 1.8-4.3), diabetes (aOR 2.0, 95%CI: 1.5-2.7), chronic lung disease (aOR 1.7, 95%CI: 1.2-2.3), and ″other chronic diseases″ (aOR 1.8, 95%CI: 1.3-2.6) compared to those without these conditions were associated with increased odds of having severe COVID-19. Conclusions: Multiple risk factors for hospitalization, ICU admission, and death were observed in this cohort from an urban setting in the southeast U.S. Improved screening and early, intensive treatment for persons with identified risk factors is urgently needed to reduce COVID-19 related morbidity and mortality.

The metabolic signaling pathways that drive pathologic tissue inflammation and damage in humans with pulmonary tuberculosis (TB) are not well understood. Using combined methods in plasma high-resolution metabolomics, lipidomics and cytokine profiling from a multicohort study of humans with pulmonary TB disease, we discovered that IL-1β-mediated inflammatory signaling was closely associated with TCA cycle remodeling, characterized by accumulation of TCA cycle intermediates such as succinate and decreases in itaconate. This inflammatory metabolic network was particularly active in persons with multidrug-resistant (MDR)-TB after receiving 2 months of ineffective treatment and was only reversed after 1 year of appropriate anti-TB chemotherapy. Both succinate and IL-1β were closely associated with increases in proinflammatory lipid signaling, including increases in the products of phospholipase A2, increased arachidonic acid formation, and metabolism of arachidonic acid to proinflammatory eicosanoids. Together, these results indicate that decreased itaconate and accumulation of succinate and other TCA cycle intermediates are important drivers of IL-1β-mediated proinflammatory eicosanoid signaling in humans with pulmonary TB disease. Host-directed therapies that mitigate such metabolic reprograming may have potential to limit excessive pulmonary inflammation and tissue damage.