Impact of Sex and Metabolic Comorbidities on Coronavirus Disease 2019 (COVID-19) Mortality Risk Across Age Groups: 66 646 Inpatients Across 613 U.S. Hospitals

Abstract

Background The relationship between common patient characteristics, such as sex and metabolic comorbidities, and mortality from COVID-19 remains incompletely understood. Emerging evidence suggests that metabolic risk factors may also vary by age. This study aimed to determine the association between common patient characteristics and mortality across age-groups among COVID-19 inpatients. Methods We performed a retrospective cohort study of patients discharged from hospitals in the Premier Healthcare Database between April – June 2020. Inpatients were identified using COVID-19 ICD-10-CM diagnosis codes. A priori-defined exposures were sex and present-on-admission hypertension, diabetes, obesity, and interactions between age and these comorbidities. Controlling for additional confounders, we evaluated relationships between these variables and in-hospital mortality in a log-binomial model. Results Among 66,646 (6.5%) admissions with a COVID-19 diagnosis, across 613 U.S. hospitals, 12,388 (18.6%) died in-hospital. In multivariable analysis, male sex was independently associated with 30% higher mortality risk (aRR, 1.30, 95% CI: 1.26 – 1.34). Diabetes without chronic complications was not a risk factor at any age (aRR 1.01, 95% CI: 0.96 – 1.06), and hypertension without chronic complications was only a risk factor in 20-39 year-olds (aRR, 1.68, 95% CI: 1.17 – 2.40). Diabetes with chronic complications, hypertension with chronic complications, and obesity were risk factors in most age-groups, with highest relative risks among 20-39 year-olds (respective aRRs 1.79, 2.33, 1.92; p-values ≤ 0.002). Conclusions Hospitalized men with COVID-19 are at increased risk of death across all ages. Hypertension, diabetes with chronic complications, and obesity demonstrated age-dependent effects, with the highest relative risks among adults aged 20-39.

Association of Toll-like receptor 7 variants with life-threatening COVID-19 disease in males: findings from a nested case-control study

“…Stokes EK et al reported that male patients show more severe clinical manifestations than females with a statistically significant (p<0.00001) higher prevalence of hospitalizations (16% versus 12%), ICU admissions (3% versus 2%), and deaths (6% versus 5%) 3 . These results are in line with other reports indicating that gender may influence disease outcome 4,5 .…”

“…. 5×105 PBMC from COVID-19 patients 6 months after recovery and six unaffected male and female controls were stimulated for hours with the TLR7 agonist imiquimod at 5 μg/mL or cell culture medium. Total RNA extraction was performed with RNeasy Plus Mini kit and gDNA eliminator mini spin columns (QIAGEN ® , Hilden, Germany), following the manufacturer's instructions.…”

Low birth weight as a potential risk factor for severe COVID-19 in adults

“…Results confirmed our working hypothesis, which was aligned with a long-standing research line in this field 11,12,18,19,37 . Besides, results confirmed previous studies showing a strong predictive value for severe COVID-19 of older age, male sex and coexisting conditions such as hypertension [3][4][5][6][7][8][25][26][27][28][29][30][31] . The fact that we studied non-elderly adults (≤ 70 years) may have limited the identification of significant associations with other reported coexisting conditions such as chronic lung disease 2,[6][7][8]27 , diabetes [2][3][4][5]7,8,25,26,30,32 , obesity 8,31,33 or cancer 3,34 .…”

“…Previous studies. Despite the large number of studies on prognostic factors for severe COVID-19 [3][4][5][6][7][8][25][26][27][28][29][30][31][32][33][34][35][36] , to our knowledge no previous study has investigated the predictive role of early life events as a risk factor for severe COVID-19 in adulthood. Results confirmed our working hypothesis, which was aligned with a long-standing research line in this field 11,12,18,19,37 .…”

Associations Between Structural and Social Determinants of Health With COVID Infection Rates at a Safety Net Hospital.

“…13 Goodman et al in a cross-sectional United States population demonstrated that men, hypertension and obesity, age 20-39 years were associated with the highest mortality in hospitalized patients. 14 Zhang et al from Wuhan epicenter demonstrated that male sex, a severe COVID-19 condition, expectoration, muscle ache, and decreased albumin were independent risk factors for mortality. 15 Currently, there is no effective therapy for COVID-19 infection and the vaccination roll-out has just begun and would take more than 6 months before showing any impact.…”