Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis

Treating Adolescents with Social Anxiety Disorder in School: An Attention Control Trial

Background: Anxiety disorders are often undetected and untreated in adolescents. This study evaluates the relative efficacy of a school-based, cognitive-behavioral intervention compared to an educational-supportive treatment for adolescents with social anxiety disorder. Methods: Thirty-six students (30 females), ages 14 to 16, were randomized to a 12-week specific intervention, Skills for Social and Academic Success (SASS), or a credible attention control matched for structure and contact, conducted in school. Results: Independent evaluations and adolescent self-reports indicated significant reduction in social anxiety for SASS compared to the control group. Parent reports of their children\u27s social anxiety did not discriminate between treatments. In the specific intervention, 59%, compared to 0% in the control, no longer met criteria for social anxiety disorder following treatment. Superiority of the SASS intervention was maintained 6 months after treatment cessation. Conclusions: The study provides evidence that intervention for social anxiety disorder that emphasizes exposure and social skills is efficacious. Results indicate that clinical improvement is sustained for at least 6 months, and that, overall, adolescents with social anxiety disorder do not respond to non-specific treatment. This investigation has public health implications by demonstrating that effective interventions can be transported to nonclinical settings

The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system

10.1073/pnas.1314702110Proceedings of the National Academy of Sciences of the United States of America1105120651-20656PNAS