RESUMO
ObjectiveTo investigate if obstructive sleep apnoea (OSA) is an independent risk factor for severe COVID-19. To examine whether the risk for contracting COVID-19 is elevated among OSA patients. Design and settingRegistry based retrospective case-control study using Finnish nationwide health registries and the FinnGen Study cohort. ParticipantsInformation regarding OSA diagnosis and COVID-19 infection was extracted from the FinnGen study (N=260,405) with a total of 305 patients who had a recorded PCR-validated COVID-19 infection including 26 (8.5%) individuals who were also OSA patients. Severe COVID-19 (N=83; 27.2%) was defined as an infection requiring hospitalization. Among the hospitalized individuals there were 16 (19.3%) with OSA diagnosis. In addition, we also included in our analysis previously reported risk factors for both severe COVID-19 or risk factors and comorbidities for OSA from FinnGen. Main outcome measuresOSA diagnosis, information concerning COVID-19 infection such as hospitalization, were derived from Finnish National Hospital Discharge Registry, Causes of Death Registry and the National Infectious Diseases Registry. ResultsWe show that OSA is a risk factor for COVID-19 hospitalization independent from age, sex, body mass index (BMI), hypertension, diabetes, coronary heart disease (CHD), asthma and chronic obstructive pulmonary disease (COPD), (p-unadjusted=1.04x10-4, OR-adjusted=5.24 [95%CI 1.33 to 23.43], p-adjusted=0.022). OSA was not associated with the risk of contracting COVID-19 (p=0.49). ConclusionWhile an OSA patients risk of contracting COVID-19 is the same as non-OSA individuals, the OSA patients have a five-fold risk to be hospitalized when affected by COVID-19 than non-OSA individuals. Our findings suggest that, in assessment of patients with suspected or confirmed COVID-19 infection, OSA needs to be recognized as one of the comorbidity risk factors for developing a severe form of the disease.
RESUMO
The ASXL genes (ASXL1, ASXL2, and ASXL3) participate in body patterning during embryogenesis and encode proteins involved in epigenetic regulation and assembly of transcription factors to specific genomic loci. Germline de novo truncating variants in ASXL1 and ASXL3 have been respectively implicated in causing Bohring-Opitz and Bainbridge-Ropers syndromes, which result in overlapping features of severe intellectual disability and dysmorphic features. ASXL2 has not yet been associated with a human Mendelian disorder. In this study, we performed whole-exome sequencing in six unrelated probands with developmental delay, macrocephaly, and dysmorphic features. All six had de novo truncating variants in ASXL2. A careful review enabled the recognition of a specific phenotype consisting of macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties, hypotonia, and developmental disabilities. Although overlapping features with Bohring-Opitz and Bainbridge-Ropers syndromes exist, features that distinguish the ASXL2-associated condition from ASXL1- and ASXL3-related disorders are macrocephaly, absence of growth retardation, and more variability in the degree of intellectual disabilities. We were also able to demonstrate with mRNA studies that these variants are likely to exert a dominant-negative effect, given that both alleles are expressed in blood and the mutated ASXL2 transcripts escape nonsense-mediated decay. In conclusion, de novo truncating variants in ASXL2 underlie a neurodevelopmental syndrome with a clinically recognizable phenotype. This report expands the germline disorders that are linked to the ASXL genes.
