ABSTRACT
Importance The ACE D allele is more prevalent among African Americans (AA) compared to other races/ethnicities and has previously been associated with severe COVID-19 pathogenesis through excessive ACE1 activity. ACE-I/ARBs may counteract this mechanism, but their association with COVID-19 outcomes has not been specifically tested in the AA population. Objectives To determine whether the use of ACE-I/ARBs is associated with COVID-19 in-hospital mortality in AA compared with non-AA population. Design, Setting, and Participants In this observational, retrospective study, patient-level data were extracted from the Mount Sinai Health System’s (MSHS) electronic medical record (EMR) database, and 6,218 patients with a laboratory-confirmed COVID-19 diagnosis from February 24 to May 31, 2020 were identified as ACE-I/ARB users. Exposures Patients with an active prescription from January 1, 2019 up to the date of admission for ACE-I/ARB (outpatient use) and patients administered ACE-I/ARB during hospitalization (in-hospital use) were identified. Main Outcomes and Measures The primary outcome was in-hospital mortality, assessed in the entire, AA, and non-AA population. Results Of the 6,218 COVID-19 patients, 1,138 (18.3%) were ACE-I/ARB users. In a multivariate logistic regression model, ACE-I/ARB use was independently associated with reduced risk of in-hospital mortality in the entire population (OR, 0.655; 95% CI, 0.505-0.850; P=0.001), AA population (OR, 0.44; 95% CI, 0.249-0.779; P=0.005), and non-AA population (OR, 0.748, 95% CI, 0.553-1.012, P=0.06). In the AA population, in-hospital use of ACE-I/ARBs was associated with improved mortality (OR, 0.378; 95% CI, 0.188-0.766; P=0.006) while outpatient use was not (OR, 0.889; 95% CI, 0.375-2.158; P=0.812). When analyzing each medication class separately, ARB in-hospital use was significantly associated with reduced in-hospital mortality in the AA population (OR, 0.196; 95% CI, 0.074-0.516; P=0.001), while ACE-I use was not associated with impact on mortality in any population. Conclusion and Relevance In-hospital use of ARBs was associated with a significant reduction in in-hospital mortality among COVID-19-positive AA patients. These results support further investigation of ARBs to improve outcomes in AA patients at high risk for COVID-19-related mortality.
Subject(s)
COVID-19ABSTRACT
Importance: Alpha-1-adrenergic receptor antagonists (1-blockers) can abrogate pro-inflammatory cytokines and may improve outcomes among patients with respiratory infections. Repurposing readily available drugs such as 1-blockers could augment the medical response to the COVID-19 pandemic. Objective: To evaluate the association between 1-blocker exposure and COVID-19 mortality Design: Real-world evidence study Setting: Patient level data with 32,355 records tested for SARS-CoV-2 at the Mount Sinai Health System including 8,442 laboratory-confirmed cases extracted from five member hospitals in the New York City metropolitan area. Participants: 2,627 men aged 45 or older admitted with COVID-19 between February 24 and May 31, 2020 Exposures: 1-blocker use as an outpatient or while admitted for COVID-19 Main Outcomes and Measures: In-hospital mortality Results: Men exposed to 1-blockers (N=436) were older (median age 73 vs. 64 years, P<0.001) and more likely to have comorbidities than unexposed men (N=2,191). Overall, 758 (28.9%) patients died in hospital, 1,589 (60.5%) were discharged, and 280 (10.7%) were still hospitalized as of May 31, 2020. Outpatient exposure to 1-blockers was not associated with COVID-19 hospital outcomes, though there was a trend towards significance (OR 0.749, 95% CI 0.527-1.064; P=0.106). Conversely, inpatient use of 1-blockers was independently associated with improved in-hospital mortality in both multivariable logistic (OR 0.633, 95% CI 0.434-0.921; P=0.017) and Cox regression analyses (HR 0.721, 95% CI 0.572-0.908; P=0.006) adjusting for patient demographics, comorbidities, and baseline vitals and labs. Age-stratified analyses suggested greater benefit from inpatient 1-blocker use among younger age groups: Age 45-65 OR 0.384, 95% CI 0.164-0.896 (P=0.027); Age 55-75 OR 0.511, 95% CI 0.297-0.880 (P=0.015); Age 65-89 OR 0.810, 95% CI 0.509-1.289 (P=0.374). Conclusions and Relevance: Inpatient 1-blocker use was independently associated with improved COVID-19 mortality among hospitalized men. Clinical trials to assess the therapeutic value of 1-blockers in COVID-19 are warranted.
Subject(s)
COVID-19 , Respiratory Tract InfectionsABSTRACT
Epidemiological studies suggest that men exhibit a higher mortality rate to COVID-19 than women, yet the underlying biology is largely unknown. Here, we seek to delineate sex differences in the gene expression of viral entry proteins ACE2 and TMPRSS2, and host transcriptional responses to SARS-CoV-2 through large-scale analysis of genomic and clinical data. We first compiled 220,000 human gene expression profiles from three databases and completed the meta-information through machine learning and manual annotation. Large scale analysis of these profiles indicated that male samples show higher expression levels of ACE2 and TMPRSS2 than female samples, especially in the older group (>60 years) and in the kidney. Subsequent analysis of 6,031 COVID-19 patients at Mount Sinai Health System revealed that men have significantly higher creatinine levels, an indicator of impaired kidney function. Further analysis of 782 COVID-19 patient gene expression profiles taken from upper airway and blood suggested men and women present distinct expression changes. Computational deconvolution analysis of these profiles revealed male COVID-19 patients have enriched kidney-specific mesangial cells in blood compared to healthy patients. Together, this study suggests biological differences in the kidney between sexes may contribute to sex disparity in COVID-19.
Subject(s)
COVID-19 , Kidney DiseasesABSTRACT
COVID-19 is a novel threat to human health worldwide. There is an urgent need to understand patient characteristics of having COVID-19 disease and evaluate markers of critical illness and mortality. Objective: To assess association of clinical features on patient outcomes. Design, Setting, and Participants: In this observational case series, patient-level data were extracted from electronic medical records for 28,336 patients tested for SARS-CoV-2 at the Mount Sinai Health System from 2/24/ to 4/15/2020, including 6,158 laboratory-confirmed cases. Exposures: Confirmed COVID-19 diagnosis by RT-PCR assay from nasal swabs. Main Outcomes and Measures: Effects of race on positive test rates and mortality were assessed. Among positive cases admitted to the hospital (N = 3,273), effects of patient demographics, hospital site and unit, social behavior, vital signs, lab results, and disease comorbidities on discharge and death were estimated. Results: Hispanics (29%) and African Americans (25%) had disproportionately high positive case rates relative to population base rates (p<2e-16); however, no differences in mortality rates were observed in the hospital. Outcome differed significantly between hospitals (Gray's T=248.9; p<2e-16), reflecting differences in average baseline age and underlying comorbidities. Significant risk factors for mortality included age (HR=1.05 [95% CI, 1.04-1.06]; p=1.15e-32), oxygen saturation (HR=0.985 [95% CI, 0.982-0.988]; p=1.57e-17), care in ICU areas (HR=1.58 [95% CI, 1.29-1.92]; p=7.81e-6), and elevated creatinine (HR=1.75 [95% CI, 1.47-2.10]; p=7.48e-10), alanine aminotransferase (ALT) (HR=1.002, [95% CI 1.001-1.003]; p=8.86e-5) and body-mass index (BMI) (HR=1.02, [95% CI 1.00-1.03]; p=1.09e-2). Asthma (HR=0.78 [95% CI, 0.62-0.98]; p=0.031) was significantly associated with increased length of hospital stay, but not mortality. Deceased patients were more likely to have elevated markers of inflammation. Baseline age, BMI, oxygen saturation, respiratory rate, white blood cell (WBC) count, creatinine, and ALT were significant prognostic indicators of mortality. Conclusions and Relevance: While race was associated with higher risk of infection, we did not find a racial disparity in inpatient mortality suggesting that outcomes in a single tertiary care health system are comparable across races. We identified clinical features associated with reduced mortality and discharge. These findings could help to identify which COVID-19 patients are at greatest risk and evaluate the impact on survival.