ABSTRACT
Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
Subject(s)
COVID-19 , Genome-Wide Association Study , Female , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , COVID-19/genetics , Sex Characteristics , Genetic Loci , Genetic Predisposition to DiseaseABSTRACT
Resumen Introducción: Klebsiella pneumoniae produce enzimas como Betalactamasas de Espectro Extendido (BLEE) y Carbapenemasas. Estas enzimas tienen implicancia en las Unidades de Cuidados Intensivos (UCI), porque posibilitan la supervivencia de especies bacterianas a condiciones desfavorables y por ende, facilitan su permanencia en ambiente intrahospitalario. Existe evidencia de presencia de Klebsiella pneumoniae en UCI, en muestras procedentes de: pacientes, personal de salud, habitación, lavamanos y fórmulas nutricionales. Objetivo: Evaluar el perfil de resistencia de los aislamientos de Klebsiella pneumoniae en una UCI de Paraguay. Material y métodos: Estudio descriptivo observacional, transversal. Se recolectaron 200 muestras (124 fórmulas enterales, 40 ambiente y 36 pacientes). Variables analizadas: origen de muestra, presencia del germen, producción de enzimas y perfil de resistencia. Resultados: Se aisló Klebsiella pneumoniae en 14% de las muestras. Se identificó al germen en: 25% pacientes, 12,9% fórmulas enterales y 7,5% ambiente. Se observó producción de BLEE en 85,7% de las cepas, con perfiles de resistencia idénticos, y producción de carbapenemasas en 14,3% de las cepas, con perfiles de resistencia diferentes. Conclusión: la presencia y los perfiles de resistencia de Klebsiella pneumoniae en las tres clases de muestras estudiadas, sugieren transferencia de genes de resistencia y diseminación del germen en UCI.
Abstract Introduction: Klebsiella pneumoniae produces enzymes such as Extended Spectrum Betalactamases (ESBL) and Carbapenemases. These enzymes have implica tions in Intensive Care Units (ICU), because they enable the survival of bacterial species under unfavorable conditions and, therefore, facilitate their permanence in the hospital environment. There is evidence of the presence of Klebsiella pneumoniae in the ICU, in samples from: patients, health staff, room, sink, and nutri tional formulas. Objective: To evaluate the resistance profile of Klebsiella pneumoniae isolates in an ICU in Paraguay. Material and methods: descriptive, observational, cross-sectional study. 200 samples were collected (124 enteral formulas, 40 ambient and 36 patients). Variables analyzed: sample origin, presence of the germ, enzyme production and resistance profile. Results: Klebsiella pneumoniae was isolated in 14% of the samples. The germ was identified in: 25% patients, 12.9% enteral formulas and 7.5% environment. Pro duction of ESBL was observed in 85.7% of the strains, with identical resistance profiles, and production of carbapenemases in 14.3% of the strains, with different resistance profiles. Conclusion: the presence and resistance profiles of Klebsiella pneumoniae in the three classes of samples studied, suggest transfer of resistance genes and disse mination of the germ in ICU.
