ABSTRACT
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 genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 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 region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes 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 including non-Caucasian individuals, 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.
Subject(s)
COVID-19 , Humans , COVID-19/genetics , SARS-CoV-2/genetics , Genome-Wide Association Study , Haplotypes , Polymorphism, GeneticABSTRACT
Objectives: Multiple myeloma (MM) is one of the hematologic malignancies with a greater delay in diagnosis. Laboratories receive numerous MM screening test requests without a specific suspicion, which entails a substantial workload and reduces the efficiency of laboratories. Objective: to increase the efficacy of MM screening protocols. Methods: The results of serum protein electrophoresis (SPEP), serum protein immunofixation electrophoresis (SIFE), urine protein immunofixation electrophoresis, and serum free light chain assays of 75 patients with MM, three with amyloidosis, and a patient with solitary plasmocytoma were collected. The frequency of a set of biochemical alterations in these patients was compared with that in controls (n=120). A validation of the screening algorithm was carried out in 261 consecutive patients with a clinical or analytical suspicion of MM. Results: SPEP+SFLC or SIFE+SFLC (98% sensitivity) were the screening algorithms with the highest sensitivity. Prospectively, the SPEP + SFLC detected 27 of the 28 confirmed cases of MG and saved 15 h of work. Alterations in five of the six parameters studied were more frequent in the study group, with a cumulative value of ≥3 parameters altered (61.1 vs. 1.7%) (positive predictive value: 85%; negative predictive value: 94%). Conclusions: The SPEP+SFLC screening protocol demonstrated the highest sensitivity and was the least time-consuming protocol. In addition, this protocol improves diagnostic sensitivity and laboratory performance.
ABSTRACT
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