ABSTRACT
Background: We conducted a retrospective cohort study on COVID-19 patients with and without dementia by extracting data from the HCA Healthcare Enterprise Data Warehouse between January-September 2020. Aims: To describe the role of patients' baseline characteristics specifically dementia in determining overall health outcomes in COVID-19 patients. Methods: We grouped in-patients who had ICD-10 codes for dementia (DM) with age and gender-matched (1:2) patients without dementia (ND). Our primary outcome variables were in-hospital mortality, length of stay, Intensive Care Unit (ICU) admission, ICU-free days, mechanical ventilation (MV) use, MV-free days and 90-day re-admission. Results: Matching provided similar age and sex in DM and ND groups. BMI (median, 25.8 vs. 27.6) and proportion of patients who had smoked (23.3 vs. 31.3%) were lower in DM than in ND patients. The median (IQR) Elixhauser Comorbidity Index was higher in dementia patients 7 (5-10) vs. 5 (3-7, p < 0.01). Higher mortality was observed in DM group (30.8%) vs. ND group (26.4%, p < 0.01) as an unadjusted univariate analysis. The 90-day readmission was not different (32.1 vs. 31.8%, p = 0.8). In logistic regression analysis, the odds of dying were not different between patients in DM and ND groups (OR = 1.0; 95% CI 0.86-1.17), but the odds of ICU admissions were significantly lower for dementia patients (OR = 0.58, 95% CI 0.51-0.66). Conclusions: Our data showed that COVID-19 patients with dementia did not fare substantially worse, but in fact, fared better when certain metrics were considered.
ABSTRACT
TMPRSS13 is a member of the type II transmembrane serine protease (TTSP) family. Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. Importantly, the catalytic competence of TMPRSS13 is essential for stem region cleavage, suggesting an autonomous mechanism of action. Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. Mutation of R223 causes a reduction in the aforementioned functional processing steps of TMPRSS13. These data provide further insight into the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13. Additionally, the data suggest the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions.