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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.

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]

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) 2024 APA, all rights reserved).