SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Speech-in-Noise Testing:An Introduction for Audiologists

Speech-in-noise testing has been proposed as a useful part of the audiometric test battery dating back to the earliest years of the field of audiology. Many speech-in-noise tests have been developed and used to varying degrees. However, multiple barriers have prevented speech-in-noise testing from being used widely in the clinic. The purpose of this article is to provide a resource to audiologists and other hearing health professionals who want to know (1) what tests are available for use, (2) the rationale behind specific tests, and (3) important considerations when selecting one or more tests to use clinically. In addition, data are presented for four speech-in-noise tests with the purpose of comparing outcomes as a function of age and hearing status. The four tests (QuickSIN, Words in Noise [WIN], Listening in Spatialized Noise-Sentences [LiSN-S], and Coordinate Response Measure [CRM]) were completed by 30 individuals from three groups: 10 young adults with normal hearing, 10 older adults with normal hearing, and 10 older adults with hearing loss. The results suggest that, despite significant differences in performance between groups, group overlap was present such that some individuals from one group performed similar to some individuals of other groups; therefore, individual performance was more important than associated group. When selecting an appropriate speech-in-noise test to use clinically, audiologists should carefully consider the purpose of their testing and the type of information they desire as an outcome. A quick-resource table and appendix is provided to aid audiologists and other health professionals in their selection of an appropriate speech-in-noise test.</p

How does social support enhance resilience in the trauma-exposed individual?

Although most resilience science has focused on individual-level psychosocial factors that promote individual resilience, theorists and researchers have begun to examine neurobiological and systems-level factors implicated in resilience. In this commentary we argue that the development of effective interventions to enhance resilience necessitates understanding that resilience in the individual is dependent on multiple layers of society. Further, we suggest that there is a bidirectional relationship between systems-level resilience (i.e., resilience of romantic partners, family members, neighborhoods, and larger social contexts) and individual resilience. We suggest directions for future research and interventions, with the goal of stimulating research efforts that address these questions among trauma-exposed individuals

Moral distress in frontline healthcare workers in the initial epicenter of the COVID-19 pandemic in the United States: Relationship to PTSD symptoms, burnout, and psychosocial functioning.

IntroductionLittle is known about the relationship between moral distress and mental health problems. We examined moral distress in 2579 frontline healthcare workers (FHCWs) caring for coronavirus disease 2019 (COVID-19) patients during the height of the spring 2020 pandemic surge in New York City. The goals of the study were to identify common dimensions of COVID-19 moral distress; and to examine the relationship between moral distress, and positive screen for COVID-19-related posttraumatic stress disorder (PTSD) symptoms, burnout, and work and interpersonal functional difficulties.MethodData were collected in spring 2020, through an anonymous survey delivered to a purposively-selected sample of 6026 FHCWs at Mount Sinai Hospital; 2579 endorsed treating COVID-19 patients and provided complete survey responses. Physicians, house staff, nurses, physician assistants, social workers, chaplains, and clinical dietitians comprised the sample.ResultsThe majority of the sample (52.7%-87.8%) endorsed moral distress. Factor analyses revealed three dimensions of COVID-19 moral distress: negative impact on family, fear of infecting others, and work-related concerns. All three factors were significantly associated with severity and positive screen for COVID-19-related PTSD symptoms, burnout, and work and interpersonal difficulties. Relative importance analyses revealed that concerns about work competencies and personal relationships were most strongly related to all outcomes.ConclusionMoral distress is prevalent in FHCWs and includes family-, infection-, and work-related concerns. Prevention and treatment efforts to address moral distress during the acute phase of potentially morally injurious events may help mitigate risk for PTSD, burnout, and functional difficulties

Social connectedness as a determinant of mental health: A scoping review.

Public health and epidemiologic research have established that social connectedness promotes overall health. Yet there have been no recent reviews of findings from research examining social connectedness as a determinant of mental health. The goal of this review was to evaluate recent longitudinal research probing the effects of social connectedness on depression and anxiety symptoms and diagnoses in the general population. A scoping review was performed of PubMed and PsychInfo databases from January 2015 to December 2021 following PRISMA-ScR guidelines using a defined search strategy. The search yielded 66 unique studies. In research with other than pregnant women, 83% (19 of 23) studies reported that social support benefited symptoms of depression with the remaining 17% (5 of 23) reporting minimal or no evidence that lower levels of social support predict depression at follow-up. In research with pregnant women, 83% (24 of 29 studies) found that low social support increased postpartum depressive symptoms. Among 8 of 9 studies that focused on loneliness, feeling lonely at baseline was related to adverse outcomes at follow-up including higher risks of major depressive disorder, depressive symptom severity, generalized anxiety disorder, and lower levels of physical activity. In 5 of 8 reports, smaller social network size predicted depressive symptoms or disorder at follow-up. In summary, most recent relevant longitudinal studies have demonstrated that social connectedness protects adults in the general population from depressive symptoms and disorders. The results, which were largely consistent across settings, exposure measures, and populations, support efforts to improve clinical detection of high-risk patients, including adults with low social support and elevated loneliness

Positron emission tomography and neuropathologic estimates of fibrillar amyloid-β in a patient with down syndrome and Alzheimer disease

Background: Down syndrome appears to be associated with a virtually certain risk of fibrillar amyloid-β (Aβ) pathology by the age of 40 and a very high risk of dementia at older ages. The positron emission tomography (PET) ligand florbetapir F18 has been shown to characterize fibrillar Aβ in the living human brain and to provide a close correlation with subsequent Aβ neuropathology in individuals proximate to and after the end of life. The extent to which the most frequently used PET ligands can be used to detect fibrillar Aβ in patients with Down syndrome remains to be determined. Objectives: To characterize PET estimates of fibrillar Aβ burden in a Down syndrome patient very close to the end of life and to compare them with neuropathologic assessment made after his death. Design/Methods: With the family\u27s informed consent, florbetapir PET was used to study a 55-year-old Down syndrome patient with Alzheimer disease near the end of life; his brain was donated for neuropathologic assessment when he died 14 days later. Visual ratings of cerebral florbetapir uptake were performed by trained readers who were masked to the patient\u27s diagnosis as part of a larger study, and an automated algorithm was used to characterize regional-to-cerebellar standard uptake value ratios in 6 cerebral regions of interest. Neuropathologic assessments were performed masked to the patient\u27s diagnosis or PET measurements. Results: Visual ratings and automated analyses of the PET image revealed a heavy fibrillar Aβ burden in cortical, striatal, and thalamic regions, similar to that reported for patients with late-onset Alzheimer disease. This matched neuropathologic findings of frequent neuritic and diffuse plaques, as well as frequent amyloid angiopathy, except for neuropathologically demonstrated frequent cerebellar diffuse plaques and amyloid angiopathy that were not detected by the PET scan. Conclusions: Florbetapir PET can be used to detect increased cerebral-to-cerebellar fibrillar Aβ burden in a Down syndrome patient with Alzheimer disease, even in the presence of frequent amyloid angiopathy and diffuse plaques in the cerebellum. Additional studies are needed to determine the extent to which PET could be used to detect and to track fibrillar Aβ and to evaluate investigational Aβ-modifying treatments in the presymptomatic and symptomatic stages of Alzheimer disease. ©2011 American Medical Association. All rights reserved