Mechanisms of socioeconomic differences in COVID-19 screening and hospitalizations.

BACKGROUND: Social and ecological differences in early SARS-CoV-2 pandemic screening and outcomes have been documented, but the means by which these differences have arisen are not well understood. OBJECTIVE: To characterize socioeconomic and chronic disease-related mechanisms underlying these differences. DESIGN: Observational cohort study. SETTING: Outpatient and emergency care. PATIENTS: 12900 Cleveland Clinic Health System patients referred for SARS-CoV-2 testing between March 17 and April 15, 2020. INTERVENTIONS: Nasopharyngeal PCR test for SARS-CoV-2 infection. MEASUREMENTS: Test location (emergency department, ED, vs. outpatient care), COVID-19 symptoms, test positivity and hospitalization among positive cases. RESULTS: We identified six classes of symptoms, ranging in test positivity from 3.4% to 23%. Non-Hispanic Black race/ethnicity was disproportionately represented in the group with highest positivity rates. Non-Hispanic Black patients ranged from 1.81 [95% confidence interval: 0.91-3.59] times (at age 20) to 2.37 [1.54-3.65] times (at age 80) more likely to test positive for the SARS-CoV-2 virus than non-Hispanic White patients, while test positivity was not significantly different across the neighborhood income spectrum. Testing in the emergency department (OR: 5.4 [3.9, 7.5]) and cardiovascular disease (OR: 2.5 [1.7, 3.8]) were related to increased risk of hospitalization among the 1247 patients who tested positive. LIMITATIONS: Constraints on availability of test kits forced providers to selectively test for SARS-Cov-2. CONCLUSION: Non-Hispanic Black patients and patients from low-income neighborhoods tended toward more severe and prolonged symptom profiles and increased comorbidity burden. These factors were associated with higher rates of testing in the ED. Non-Hispanic Black patients also had higher test positivity rates.

Association of Lymphopenia With Risk of Mortality Among Adults in the US General Population.

Importance: Immune dysregulation can increase the risk of infection, malignant neoplasms, and cardiovascular disease, but improved methods are needed to identify and quantify immunologic hazard in the general population. Objective: To determine whether lymphopenia is associated with reduced survival in outpatients. Design, Setting, and Participants: This retrospective cohort study of the National Health and Nutrition Examination Survey (NHANES) included participants enrolled from January 1, 1999, to December 31, 2010, a large outpatient sample representative of the US adult population. Associations were evaluated between lymphopenia and other immunohematologic (IH) markers, clinical features, and survival during 12 years of follow-up, completed on December 31, 2011. Spearman correlations, Cox proportional hazards regression models, and Kaplan-Meier curves were used in univariable and multivariable models, allowing for nonlinear associations with bivariate cubic polynomials. Data were analyzed from September 1, 2018, through July 24, 2019. Exposures: Absolute lymphocyte counts (ALC), red blood cell distribution width (RDW), and C-reactive protein (CRP) level. Main Outcomes and Measures: All-cause survival. Results: Among the 31 178 participants, the median (interquartile range) age at baseline was 45 (30-63) years, 16 093 (51.6%) were women, 16 260 (52.2%) were nonwhite, and overall 12-year rate of survival was 82.8%. Relative lymphopenia (≤1500/µL) and severe lymphopenia (≤1000/µL) were observed in 20.1% and 3.0%, respectively, of this general population and were associated with increased risk of mortality (age- and sex-adjusted hazard ratios [HRs], 1.3 [95% CI, 1.2-1.4] and 1.8 [95% CI, 1.6-2.1], respectively) due to cardiovascular and noncardiovascular causes. Lymphopenia was also associated with worse survival in multivariable models, including traditional clinical risk factors, and this risk intensified when accompanied by bone marrow dysregulation (elevated RDW) and/or inflammation (elevated CRP level). Ten-year mortality ranged from 3.8% to 62.1% based on lymphopenia status, tertile of CRP level, and tertile of RDW. A high-risk IH profile was nearly twice as common as type 2 diabetes (19.3% and 10.0% of participants, respectively) and associated with a 3-fold risk of mortality (HR, 3.2; 95% CI, 2.6-4.0). Individuals aged 70 to 79 years with low IH risk had a better 10-year survival (74.1%) than those who were a decade younger with a high-risk IH profile (68.9%). Conclusions and Relevance: These findings suggest that lymphopenia is associated with reduced survival independently of and additive to traditional risk factors, especially when accompanied by altered erythropoiesis and/or heightened inflammation. Immune risk may be analyzed as a multidimensional entity derived from routine tests, facilitating precision medicine and population health interventions.