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In the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, epithelial populations in the distal lung expressing Angiotensin-converting enzyme 2 (ACE2) are infrequent, and therefore, the model of viral expansion and immune cell engagement remains incompletely understood. Using human lungs to investigate early host-viral pathogenesis, we found that SARS-CoV-2 had a rapid and specific tropism for myeloid populations. Human alveolar macrophages (AMs) reliably expressed ACE2 allowing both spike-ACE2-dependent viral entry and infection. In contrast to Influenza A virus, SARS-CoV-2 infection of AMs was productive, amplifying viral titers. While AMs generated new viruses, the interferon responses to SARS-CoV-2 were muted, hiding the viral dissemination from specific antiviral immune responses. The reliable and veiled viral depot in myeloid cells in the very early phases of SARS-CoV-2 infection of human lungs enables viral expansion in the distal lung and potentially licenses subsequent immune pathologies.

Ancestral SARS coronavirus-2 (SARS-CoV-2) and variants of concern (VOC) caused a global pandemic with a spectrum of disease severity. The mechanistic explaining variations related to airway epithelium are relatively understudied. Here, we biobanked airway organoids (AO) by preserving stem cell function. We optimized viral infection with H1N1/PR8 and comprehensively characterized epithelial responses to SARS-CoV-2 infection in phenotypically stable AO from 20 different subjects. We discovered Tetraspanin-8 (TSPAN8) as a facilitator of SARS-CoV-2 infection. TSPAN8 facilitates SARS-CoV-2 infection rates independently of ACE2-Spike interaction. In head-to-head comparisons with Ancestral SARS-CoV-2, Delta and Omicron VOC displayed lower overall infection rates of AO but triggered changes in epithelial response. All variants shared highest tropism for ciliated and goblet cells. TSPAN8-blocking antibodies diminish SARS-CoV-2 infection and may spur novel avenues for COVID-19 therapy.

Rationale: Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on the lung endothelium are not well defined. We hypothesized that the lung endotheliopathy of COVID-19 is caused by circulating host factors and direct endothelial infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: We aimed to determine the effects of SARS-CoV-2 or sera from patients with COVID-19 on the permeability and inflammatory activation of lung microvascular endothelial cells. Methods: Human lung microvascular endothelial cells were treated with live SARS-CoV-2; inactivated viral particles; or sera from patients with COVID-19, patients without COVID-19, and healthy volunteers. Permeability was determined by measuring transendothelial resistance to electrical current flow, where decreased resistance signifies increased permeability. Inflammatory mediators were quantified in culture supernatants. Endothelial biomarkers were quantified in patient sera. Measurements and Main Results: Viral PCR confirmed that SARS-CoV-2 enters and replicates in endothelial cells. Live SARS-CoV-2, but not dead virus or spike protein, induces endothelial permeability and secretion of plasminogen activator inhibitor 1 and vascular endothelial growth factor. There was substantial variability in the effects of SARS-CoV-2 on endothelial cells from different donors. Sera from patients with COVID-19 induced endothelial permeability, which correlated with disease severity. Serum levels of endothelial activation and injury biomarkers were increased in patients with COVID-19 and correlated with severity of illness. Conclusions: SARS-CoV-2 infects and dysregulates endothelial cell functions. Circulating factors in patients with COVID-19 also induce endothelial cell dysfunction. Our data point to roles for both systemic factors acting on lung endothelial cells and viral infection of endothelial cells in COVID-19-associated endotheliopathy.

Asthma is associated with chronic changes in the airway epithelium, a key target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many epithelial changes, including goblet cell metaplasia, are driven by the type 2 cytokine IL-13, but the effects of IL-13 on SARS-CoV-2 infection are unknown. We found that IL-13 stimulation of differentiated human bronchial epithelial cells (HBECs) cultured at air-liquid interface reduced viral RNA recovered from SARS-CoV-2-infected cells and decreased double-stranded RNA, a marker of viral replication, to below the limit of detection in our assay. An intact mucus gel reduced SARS-CoV-2 infection of unstimulated cells, but neither a mucus gel nor SPDEF, which is required for goblet cell metaplasia, were required for the antiviral effects of IL-13. Bulk RNA sequencing revealed that IL-13 regulated 41 of 332 (12%) mRNAs encoding SARS-CoV-2-associated proteins that were detected in HBECs (>1.5-fold change; false discovery rate

For the first time, data on children and adolescents with disabilities in Ireland are reported based on the Active Healthy Kids Global Alliance Para Report Card methodology. The most recent data from the last 10 years were used in the grading process (A+ to F), and indicators with insufficient data were graded as incomplete. Of the 10 indicators from the Global Matrix Para Report Cards, grades were assigned to Overall Physical Activity (F), Organized Sport (D), Active Transport (D−), Sedentary Behaviors (D−), Family & Peers (C), School (C−), Community & Environment (B−), and Government (B). Irish disability sport organizations were invited to assess the research-led audit and provided commentary around the final grading. The contextual discussion of the grades is presented through the lens of strengths, weaknesses, opportunities, and threats with the purpose being to provide direction for the reduction of physical activity disparities among children with disabilities. [ABSTRACT FROM AUTHOR]

This Open Forum is relevant for investigators who conduct research with historically understudied and marginalized populations. The authors introduce a U.S. Department of Veterans Affairs clinical trial that experienced challenges with recruitment of African American or Black veterans and was terminated for not achieving its recruitment goals. The role of power dynamics in clinical research is discussed, specifically how unequal distributions of power may create recruitment challenges. The authors summarize three lessons learned and offer recommendations for sharing power equitably between investigators and potential participants. By recounting these experiences, the authors seek to promote culturally sensitive, veteran-centered approaches to recruitment in future clinical trials. [ABSTRACT FROM AUTHOR]

As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model overexpressing the ACE2 receptor (ACE2-OE) that supports robust viral replication while maintaining 3D architecture and cellular diversity of the airway epithelium. ACE2-OE organoids were infected with SARS-CoV-2 variants and subjected to single-cell RNA-sequencing. Interferon-lambda was upregulated in cells with low-level infection while the NF-kB inhibitor alpha gene (encoding IkBa) was consistently upregulated in infected cells, and its expression positively correlated with infection levels. Confocal microscopy showed more IkBa expression in infected than bystander cells, but found concurrent nuclear translocation of NF-kB that IkBa usually prevents. Overexpressing a nondegradable IkBa mutant reduced NF-kB translocation and increased viral infection. These data demonstrate the functionality of ACE2-OE organoids in SARS-CoV-2 research and underscore that the strength of the NF-kB feedback loop in infected cells controls viral replication. [ABSTRACT FROM AUTHOR]

The article presents the Type 2 Asthma Mediator IL-13 Inhibits SARS-CoV-2 Infection of Bronchial Epithelium.

Background The impact of the COVID-19 public health social measures (PHSM) on health behaviours is poorly understood. We aimed to identify factors associated with changes in alcohol and tobacco consumption during the strictest period of PHSM 'lockdown'. Methods Logistic regression analysis was conducted using secondary data from the Central Statistics Office Social Impact Survey collected during the first lockdown in Ireland (23 April– 1 May 2020). Results Of the 1362 (33.8%) individuals that responded to the survey, 80.6% were current drinkers and 26.0% were smokers. The majority of smokers (60.9%) and drinkers (60.6%) reported no change in consumption. However, 30.5% of smokers and 22.2% of drinkers reported increased consumption. Being concerned about household stress from confinement [adjusted odds ratio (aOR) 1.9, 95% confidence interval (CI) 1.3–2.9, P  = 0.002], working from home (aOR 2.1, 95 CI 1.4–3.3, P  < 0.001) and urban living (aOR 2.0, 95 CI 1.5–2.9, P  < 0.001) were associated with increases in alcohol consumption. Feeling very nervous (aOR 2.2, 95% CI 1.2–4.0, P  = 0.009), feeling downhearted/depressed (aOR 2.4, 95% CI 1.3–4.4, P  = 0.004), being concerned about someone else's health (aOR 2.0, 95% CI 1.1–3.9, P  = 0.031), working from home (aOR 2.3, 95% CI 1.0–5.3, P  = 0.046) and increases in alcohol consumption (aOR 3.6, 95% CI 1.7–7.7, P  = 0.023) were associated with increases in tobacco consumption. Conclusion A mixed picture was evident in terms of changes in consumption among current smokers and drinkers. Increased consumption was more commonly reported than reductions. Increased consumption was associated with psychological distress and socio-economic factors. Policies and services should consider a response to widening inequalities in harmful consumption. [ABSTRACT FROM AUTHOR]

Identifying lake networks and knowing the degree of surface‐water connectivity among lakes can help scientists better understand and predict the movement of abiotic materials and biota within networks. Quantifying broad‐scale networks that include lake and stream connections is difficult computationally. Starting from the medium resolution National Hydrography Dataset's lakes, streams, and rivers, we applied a graph theory approach to identify lake networks, a set of lakes connected by streams both upstream and downstream. The LAGOS‐US NETWORKS v1 module contains four data tables, one of which includes derived surface‐water connectivity metrics for lakes (n = 86,511 lakes ≥ 1 ha in surface area) and networks (n = 898) within the conterminous United States, including dams. The NETWORKS module also includes a flow table as well as a bidirectional and a unidirectional distance table that provide the stream course distances between every connected lake. Finally, this module includes a detailed User Guide. [ABSTRACT FROM AUTHOR]

Macroscale studies of aquatic ecosystems are needed to address many contemporary broad‐scale problems related to global change, particularly to inform national‐scale environmental policies. In this data paper, we fill two important gaps in data availability for lakes at the scale of the conterminous U.S., the lack of: (1) high‐resolution geographic representations of lakes and their watersheds and (2) an open data platform to connect disparate U.S. national‐scale lake datasets. We describe the LAGOS‐US LOCUS v1.0 data module that includes a detailed User Guide, which is part of the LAGOS‐US extensible research‐ready open data platform. This platform can be used to study the 479,950 lakes and reservoirs larger than or equal to 1 ha across the entire conterminous U.S. at multiple scales of space and time. The LOCUS module includes spatially‐explicit information on lakes and their watersheds, including location information, physical characteristics, and identifiers of other important national‐scale datasets. [ABSTRACT FROM AUTHOR]

Objective: Military sexual trauma (MST) is prevalent among female veterans and is associated with deleterious health outcomes. Adaptive coping strategies (e.g., emotional support) are associated with more positive outcomes, while maladaptive strategies (e.g., substance use) are associated with greater impairment. However, research on factors that influence specific coping strategy use is limited. For women with a history of MST, expectancies about the effects of alcohol may enhance the use of maladaptive and reduce the use of adaptive strategies. The present study tested this hypothesis. Associations among MST status and two coping behaviors (emotional support, substance use) in female veterans were examined and the mediating role of positive alcohol expectancies on these relationships was tested., Method: A secondary analysis was conducted using self-report survey data from 186 female veterans in a Northeastern region. Measures included a brief screen for MST, the posttraumatic stress disorder (PTSD) Checklist for DSM-5, the Brief Cope, and the Brief Comprehensive Effects of Alcohol Questionnaire., Results: Among all respondents, positive alcohol expectancies were significantly associated with greater substance use coping, while PTSD symptom severity was negatively associated with emotional support coping. Though women with MST reported greater positive alcohol expectancies and PTSD symptom severity, the direct effects of MST on coping were not significant. Mediation was not supported in our sample., Conclusions: Alcohol expectancies may be a viable target for intervention to reduce alcohol use as a maladaptive coping strategy among female veterans. Similarly, treatment targeting PTSD symptoms, regardless of MST status, is important for enhancing the use of adaptive coping strategies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).