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 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.
ABSTRACT
Covid-19 death has a different relationship with age than is the case for other severe respiratory pathogens. The Covid-19 death rate increases exponentially with age, and the main risk factors are age itself, as well as having underlying conditions such as hypertension, diabetes, cardiovascular disease, severe chronic respiratory disease and cancer. Furthermore, the almost complete lack of deaths in children suggests that infection alone is not sufficient to cause death; rather, one must have gone through a number of changes, either as a result of undefined aspects of aging, or as a result of chronic disease. These characteristics of Covid-19 death are consistent with the multistep model of disease, a model which has primarily been used for cancer, and more recently for amyotrophic lateral sclerosis (ALS). We applied the multi-step model to data on Covid-19 case fatality rates (CFRs) from China, South Korea, Italy, Spain and Japan. In all countries we found that a plot of ln (CFR) against ln (age) was approximately linear with a slope of about 5. As a comparison, we also conducted similar analyses for selected other respiratory diseases. SARS showed a similar log-log age-pattern to that of Covid-19, albeit with a lower slope, whereas seasonal and pandemic influenza showed quite different age-patterns. Thus, death from Covid-19 and SARS appears to follow a distinct age-pattern, consistent with a multistep model of disease that in the case of Covid-19 is probably defined by comorbidities and age producing immune-related susceptibility. Identification of these steps would be potentially important for prevention and therapy for SARS-COV-2 infection.
ABSTRACT
Objetivos: Se evalúa una intervención realizada en el lugar del trabajo para facilitar el abandono del hábito tabáquico y reducir la prevalencia de fumadores entre el personal del Ayuntamiento de Sabadell. Población y métodos: Estudio preintervención y postintervención. Se realizó una encuesta para conocer la prevalencia y las características de los fumadores e invitarles a participar en un programa de deshabituación. El programa constaba de una visita individual con historia clínica, medida de monóxido de carbono en aire espirado y prescripción de terapia con sustitutos de nicotina y 12 sesiones de terapia grupal para reforzar la abstinencia a lo largo de 1 año. A los 6, 12 y 24 meses se realizaron controles para conocer la abstinencia. Con una encuesta postintervención se valoró el impacto del programa. Resultados: Se enviaron 1.203 cuestionarios con una tasa de respuesta del 51%. Un 33% (n = 204) era fumador y 101 personas iniciaron el programa. La abstinencia a los 12 meses fue del 45% y a los 24 meses del 33%, sin que se observaran diferencias según el sexo. La dependencia moderada o baja a la nicotina se asoció con una mayor probabilidad de estar abstinente a los 6 meses (odds ratio [OR] = 6,7; p = 0,01) y a los 12 meses (OR = 5,4; p = 0,05) ajustando por sexo, edad y seguimiento del tratamiento con sustitutos de nicotina. La prevalencia de fumadores en el cuestionario postintervención fue del 19%. Un 26% (n = 10) de los que habían dejado de fumar en el último año sin participar en el programa declaró haberlo dejado gracias a él. Conclusiones: Los resultados indican que este tipo de programa en un entorno laboral puede contribuir de forma notable a reducir el tabaquismo
Aims: To evaluate the effects of a worksite smoking cessation program conducted to reduce the prevalence of smokers among staff of the town council of Sabadell (Spain). Population and methods: A pre-post intervention study was conducted. A survey was performed to determine the prevalence and characteristics of smokers and to invite them to participate in a smoking cessation program. The intervention involved an individual visit with medical history, measurement of carbon monoxide in expired air and prescription of nicotine replacement therapy followed by 12 sessions of group therapy over 1 year to reinforce abstinence. Follow-up to evaluate abstinence took place at 6, 12 and 24 months. A post-intervention survey was carried out to evaluate the program's effectiveness. Results: A total of 1,203 questionnaires were sent with a response rate of 51%. Thirty-three percent of the subjects (n = 204) were smokers and 101 smokers enrolled in the program. Abstinence rates at 12 and 24 months were 45% and 33% respectively with no differences between sexes. Low and moderate nicotine dependence was associated with a greater probability of abstinence at 6 (OR = 6.7; p = 0.01) and 12 months (OR = 5.4: p = 0.05), adjusted by sex, age, and compliance with nicotine replacement therapy. The prevalence of smokers in the post-intervention questionnaire was 19%. In addition, 26% (n = 10) of subjects who quit smoking in the 12-month study period without participating in the program reported quitting because of the program. Conclusions: The results indicate that worksite smoking cessation programs can substantially contribute to reducing the prevalence of smoking
