Novel genes and sex differences in COVID-19 severity.

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.

Limitations on Participation and Their Relation to Social Determinants of Health Among Occupational Therapists and Occupational Therapy Students During Coronavirus Lockdown.

IMPORTANCE: For the first time in recent history, people worldwide have faced severe restrictions in occupations because of the measures adopted by governments to contain the coronavirus disease 2019 (COVID-19) crisis. OBJECTIVE: To determine the limitations on participation of occupational therapists and occupational therapy students during "lockdown" and their impact on social determinants of health. DESIGN: A cross-sectional, descriptive study conducted via an online survey. PARTICIPANTS: A total of 488 occupational therapists and occupational therapy students in North America, South America, and Europe. Outcomes and Measures: A questionnaire consisting of the World Health Organization Disability Assessment Schedule 2.0 of the International Classification of Functioning, Disability and Health and items developed to assess the impact of lockdown on daily life was emailed to occupational therapy professional associations, organizations, and universities between April and June 2020. It was available in English, Spanish, and Portuguese and met all the parameters listed in the Declaration of Helsinki. RESULTS: The roles and routines of people across the developed world have been affected by lockdown measures. The study shows marked differences between participants in the domains of getting along and life activities, as well as influence on the environment. Moreover, South American participants experienced these difficulties to a greater extent than European participants. CONCLUSIONS AND RELEVANCE: This study quantifies the limitations in the participation of occupational therapists and occupational therapy students and the relationship of occupation to social determinants of health. What This Article Adds: The results of this research corroborate the relationship between health and occupation and highlight elements, such as the environment and context, that are important in occupational therapy. Therapists' ability to analyze occupation in relation to contextual and cultural factors will benefit clients.