ABSTRACT
PURPOSE: Since the declaration of COVID-19 as a pandemic, a wide between-country variation was observed regarding in-hospital mortality and its predictors. Given the scarcity of local research and the need to prioritize the provision of care, this study was conducted aiming to measure the incidence of in-hospital COVID-19 mortality and to develop a simple and clinically applicable model for its prediction. METHODS: COVID-19-confirmed patients admitted to the designated isolation areas of Ain-Shams University Hospitals (April 2020-February 2021) were included in this retrospective cohort study (n = 3663). Data were retrieved from patients' records. Kaplan-Meier survival and Cox proportional hazard regression were used. Binary logistic regression was used for creating mortality prediction models. RESULTS: Patients were 53.6% males, 4.6% current smokers, and their median age was 58 (IQR 41-68) years. Admission to intensive care units was 41.1% and mortality was 26.5% (972/3663, 95% CI 25.1-28.0%). Independent mortality predictors-with rapid mortality onset-were age ≥ 75 years, patients' admission in critical condition, and being symptomatic. Current smoking and presence of comorbidities particularly, obesity, malignancy, and chronic haematological disorders predicted mortality too. Some biomarkers were also recognized. Two prediction models exhibited the best performance: a basic model including age, presence/absence of comorbidities, and the severity level of the condition on admission (Area Under Receiver Operating Characteristic Curve (AUC) = 0.832, 95% CI 0.816-0.847) and another model with added International Normalized Ratio (INR) value (AUC = 0.842, 95% CI 0.812-0.873). CONCLUSION: Patients with the identified mortality risk factors are to be prioritized for preventive and rapid treatment measures. With the provided prediction models, clinicians can calculate mortality probability for their patients. Presenting multiple and very generic models can enable clinicians to choose the one containing the parameters available in their specific clinical setting, and also to test the applicability of such models in a non-COVID-19 respiratory infection.
Subject(s)
COVID-19 , Male , Humans , Middle Aged , Aged , Female , Retrospective Studies , SARS-CoV-2 , Hospitals, University , Egypt , Hospital MortalityABSTRACT
Background: A deep understanding of the causes of liability to SARS-CoV-2 is essential to develop new diagnostic tests and therapeutics against this serious virus in order to overcome this pandemic completely. In the light of the discovered role of antimicrobial peptides [such as human b-defensin-2 (hBD-2) and cathelicidin LL-37] in the defense against SARS-CoV-2, it became important to identify the damaging missense mutations in the genes of these molecules and study their role in the pathogenesis of COVID-19. Methods: We conducted a comprehensive analysis with multiple in silico approaches to identify the damaging missense SNPs for hBD-2 and LL-37; moreover, we applied docking methods and molecular dynamics analysis to study the impact of the filtered mutations. Results: The comprehensive analysis reveals the presence of three damaging SNPs in hBD-2; these SNPs were predicted to decrease the stability of hBD-2 with a damaging impact on hBD-2 structure as well. G51D and C53G mutations were located in highly conserved positions and were associated with differences in the secondary structures of hBD-2. Docking-coupled molecular dynamics simulation analysis revealed compromised binding affinity for hBD-2 SNPs towards the SARS-CoV-2 spike domain. Different protein-protein binding profiles for hBD-2 SNPs, in relation to their native form, were guided through residue-wise levels and differential adopted conformation/orientation. Conclusions: The presented model paves the way for identifying patients prone to COVID-19 in a way that would guide the personalization of both the diagnostic and management protocols for this serious disease.