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integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs.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.

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2 + TMPRSS2 + cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

Growing evidence supports a role for the gut microbiome in the pathogenesis and course of food allergy. Gut dysbiosis may precede the development of food allergy, and the timing of such dysbiosis is critical. Gut microbiota associated with individual food allergies may be distinct. Murine models suggest that gut microbiota affect food allergy susceptibility by modulating type 2 immunity, influencing immune maturation and tolerance, regulating basophil populations, and promoting intestinal barrier function. Ongoing and future interventional clinical trials of probiotics, prebiotics, synbiotics, and fecal microbiota transfer can help translate our understanding of the gut microbiome in food allergy to clinical practice. Robust and consistent study design, multidimensional profiling, and systems biology approaches will further advance our understanding of the microbiome in food allergy.

Background: The novel coronavirus and its effect on our society are unprecedented. Given the recent pandemic, numerous measures have been taken to protect our communities. We sought to understand our school community's knowledge and the measures that were taken by our school for our safety.Objective: Our objective was to describe the overall understanding and attitudes of 8–12th grade students from a single institution during the initial phase of the Wisconsin's Governor's stay-at-home order.Methods: A voluntary web-based survey was communicated to 8–12th grade students through their online school portal. Data were collected and analyzed using SurveyMonkey.Results: There was a 20.2% response rate. Answers regarding the coronavirus, spread, and response to the coronavirus pandemic showed a high level of understanding of the virus and the actions necessary to prevent its spread.Conclusion: Eight-twelfth grade students have a high level of understanding of the virus, its effects, and the safety measures implemented to protect society.

TP53 is the most frequently mutated gene across many cancers and is associated with shorter survival in non-small cell lung cancer (NSCLC). To understand how TP53-mutant (TP53mut) malignant cells interact with the tumor microenvironment (TME) at a molecular, cellular, and tissue level, we built a multi-omic cellular and spatial tumor atlas of 23 treatment-naive NSCLC human tumors. We identified significant differences in malignant expression programs and spatial cell-cell interactions between TP53mut and TP53WT tumors and found that highly-entropic TP53mut malignant cells lose alveolar identity and coincide with an increased abundance of exhausted T cells and immune checkpoint interactions with implications for response to checkpoint blockade. We also identified a multicellular, pro-metastatic, hypoxic tumor niche, where highly-plastic, TP53mut malignant cells expressing epithelial to mesenchymal transition (EMT) programs associate with SPP1+ myeloid cells and collagen-expressing cancer-associated fibroblasts. Our approach can be further applied to investigate mutation-specific TME changes in other solid tumors.