RESUMO
Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic [~]0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
RESUMO
BACKGROUND: The comparative accuracy and discriminatory power of three validated rules for predicting clinically relevant outcomes other than mortality in patients hospitalized with community-acquired pneumonia (CAP) are unknown. METHODS: We prospectively compared the newly developed severe community-acquired pneumonia (SCAP) score, pneumonia severity index (PSI), and the British Thoracic Society confusion, urea > 7 mmol/L, respiratory rate > or = 30 breaths/min, BP < 90 mm Hg systolic or < 60 mm Hg diastolic, age > or = 65 years (CURB-65) rule in an internal validation cohort of 1,189 consecutive adult inpatients with CAP from one hospital and an external validation cohort of 671 consecutive adult inpatients from three other hospitals. Major adverse outcomes were admission to ICU, need for mechanical ventilation, progression to severe sepsis, or treatment failure. Mean hospital length of stay (LOS) was also evaluated. The rules were compared based on sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic. RESULTS: The rate of all adverse outcomes and hospital LOS increased directly with increasing SCAP, PSI, or CURB-65 scores (p < 0.001) in both cohorts. Patients classified as high risk by the SCAP score showed higher rates of adverse outcomes (ICU admission, 35.8%; mechanical ventilation, 16.4%; severe sepsis, 98.5%; treatment failure, 22.4%) than PSI and CURB-65 high-risk classes. The discriminatory power of SCAP, as measured by AUC, was 0.75 for ICU admission, 0.76 for mechanical ventilation, 0.79 for severe sepsis, and 0.61 for treatment failure in the external validation cohort. AUC differences with PSI or CURB-65 were found. CONCLUSIONS: The SCAP score is as accurate or better than other current scoring systems in predicting adverse outcomes in patients hospitalized with CAP while helping classify patients into different categories of increasing risk for potentially closer monitoring.
