Neighborhood Poverty and Clinic Attendance in the Michigan Screening and Intervention for Glaucoma and Eye Health through Telemedicine Program.

PRECIS: Higher neighborhood-level poverty is associated with greater odds of missing a free eye disease screening appointment, underscoring the importance of community-based interventions to address upstream social determinants of health. PURPOSE: To investigate the association between neighborhood-level characteristics and attendance for a free eye disease screening. PATIENTS AND METHODS: The MI-SIGHT program is conducted in two community clinics in Southeastern Michigan. Participant-level demographics were extracted from electronic health records. Neighborhood level-characteristics including Area Deprivation Index (ADI), median household income (HHI), percent of households with >30% rent burden, percent of households without vehicles, percent of households in subsidized housing, and energy burden were obtained from the Wisconsin Neighborhood Atlas and the United States census. Logistic regression was used to model the probability of clinic visit attendance, which was the main outcome measure. RESULTS: 1431 participants were scheduled for screening appointments between July 2020 to November 2021, with a no-show rate of 23%. Individuals lived an average of 7.7 miles from each clinic (SD=8.1) and in neighborhoods with a mean ADI of 6.8 (SD=3.2, 1-10 scale where 10 is the most deprived). After adjusting for age, sex, race, and ethnicity, participants from neighborhoods with higher deprivation were more likely to have missed clinic visits. For example, there was an 8% higher odds of missed clinic visits for every 1-point increase in ADI (odds ratio, OR=1.08, P=0.020) and an 18% higher odds of a missed visit with every 10% increase in households without a vehicle (OR=1.18, P=0.013). CONCLUSION: Higher neighborhood-level poverty was associated with greater odds of missing a free eye disease screening appointment after adjusting for individual characteristics. Increased neighborhood-level resources are likely needed to bolster engagement in preventive eye care.

Eye Care in Federally Qualified Health Centers.

PURPOSE: To assess changes in vision care availability at Federally Qualified Health Centers (FQHCs) between 2017 and 2021 and whether neighborhood-level demographic social risk factors (SRFs) associated with eye care services provided by FQHCs. DESIGN: Secondary data analysis of the Health Resources and Services Administration (HRSA) data and 2017-2021 American Community Survey (ACS). PARTICIPANTS: Federally Qualified Health Centers. METHODS: Patient and neighborhood characteristics for SRFs were summarized. Differences in FQHCs providing and not providing vision care were compared via Wilcoxon-Mann-Whitney tests for continuous measures and chi-square tests for categorical measures. Logistic regression models were used to test the associations between neighborhood measures and FQHCs providing vision care, adjusted for patient characteristics. MAIN OUTCOME MEASURES: Odds ratios (ORs) with 95% confidence intervals (CIs) for neighborhood-level predictors of FQHCs providing vision care services. RESULTS: Overall, 28.5% of FQHCs (n = 375/1318) provided vision care in 2017 versus 32% (n = 435/1362) in 2021 with some increases and decreases in both the number of FQHCs and those with and without vision services. Only 2.6% of people who accessed FQHC services received eye care in 2021. Among the 435 FQHCs that provided vision care in 2021, 27.1% (n = 118) had added vision services between 2017 and 2021, 71.5% (n = 311) had been offering vision services since at least 2017, and 1.4% (n = 6) were newly established. FQHCs providing vision care in 2021 were more likely to be in neighborhoods with a higher percentage of Hispanic/Latino individuals (OR, 1.08, 95% CI, 1.02-1.14, P = 0.0094), Medicaid-insured individuals (OR, 1.08, 95% CI, 1.02-1.14, P = 0.0120), and no car households (OR, 1.07, 95% CI, 1.01-1.13, P = 0.0142). However, FQHCs with vision care, compared to FQHCs without vision care, served a lower percentage of Hispanic/Latino individuals (27.2% vs. 33.9%, P = 0.0007), Medicaid-insured patients (42.8% vs. 46.8%, P < 0.0001), and patients living at or below 100% of the federal poverty line (61.3% vs. 66.3%, P < 0.0001). CONCLUSIONS: Vision care services are available at a few FQHCs, localized to a few states. Expanding eye care access at FQHCs would meet patients where they seek care to mitigate vision loss to underserved communities. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Place-Based Measures of Inequity and Vision Difficulty and Blindness.

Importance: Known social risk factors associated with poor visual and systemic health in the US include segregation, income inequality, and persistent poverty. Objective: To investigate the association of vision difficulty, including blindness, in neighborhoods with measures of inequity (Theil H index, Gini index, and persistent poverty). Design, Setting, and Participants: This cross-sectional study used data from the 2012-2016 American Community Survey and 2010 US census tracts as well as Theil H index, Gini index, and persistent poverty measures from PolicyMap. Data analysis was completed in July 2023. Main Outcomes and Measures: The main outcome was the number of census tract residents reporting vision difficulty and blindness (VDB) and the association with the Theil H index, Gini index, or persistent poverty, assessed using logistic regression. Results: In total, 73 198 census tracts were analyzed. For every 0.1-unit increase in Theil H index and Gini index, there was an increased odds of VDB after controlling for census tract-level median age, the percentage of the population that identified as female sex, the percentage of the population that identified as a member of a racial or ethnic minority group, state, and population size (Theil H index: odds ratio [OR], 1.14 [95% CI, 1.14-1.14; P < .001]; Gini index: OR, 1.15 [95% CI, 1.15-1.15; P < .001]). Persistent poverty was associated with an increased odds of VDB after controlling for census tract-level median age, the percentage of the population that identified as female sex, the percentage of the population that identified as a member of a racial or ethnic minority group, state, and population size compared with nonpersistent poverty (OR, 1.36; 95% CI, 1.35-1.36; P < .001). Conclusions and Relevance: In this cross-sectional study, residential measures of inequity through segregation, income inequality, or persistent poverty were associated with a greater number of residents living with VDB. It is essential to understand and address how neighborhood characteristics can impact rates of VDB.

Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality.

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.RESULTSIncreasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, formation of neutrophil extracellular traps, and T cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma Igs and B cells and dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to failure of viral clearance in patients with fatal illness.CONCLUSIONOur longitudinal multiomics profiling study revealed temporal coordination across diverse omics that potentially explain the disease progression, providing insights that can inform the targeted development of therapies for patients hospitalized with COVID-19, especially those who are critically ill.TRIAL REGISTRATIONClinicalTrials.gov NCT04378777.FUNDINGNIH (5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-18); NIAID, NIH (3U19AI1289130, U19AI128913-04S1, and R01AI122220); and National Science Foundation (DMS2310836).

Measuring resilience for Chinese-speaking populations: a systematic review of Chinese resilience scales.

Introduction: Despite the rapid growth of interdisciplinary resilience research in Chinese contexts, no study has systematically reviewed individual-level measurement scales for Chinese-speaking populations. We report a systematic review of scales developed for or translated/adapted to Chinese-speaking contexts, where we assessed how widely used scales fare in terms of their psychometric qualities. Methods: Studies included in this review must have been published in peer-reviewed English or Chinese journals between 2015-2020 and included self-reported resilience scales in Chinese-speaking populations. Searches were conducted in PsycINFO, CNKI (completed in May 2021), and PubMed (completed in January 2024). We developed coding schemes for extracting relevant data and adapted and applied an existing evaluation framework to assess the most frequently used resilience scales by seven methodological criteria. Results: Analyses of 963 qualified studies suggested that Chinese resilience scales were used in a diverse range of study contexts. Among 85 unique kinds of resilience measures, we highlighted and evaluated the three most frequently used translated scales and three locally developed scales (nine scales in total including variations such as short forms). In short, resilience studies in Chinese contexts relied heavily on the translated 25-item Connor-Davidson Resilience Scale, which scored moderately on the overall quality. The locally developed Resilience Scale for Chinese Adolescents and Essential Resilience Scale received the best ratings but could use further development. Discussion: We discussed how future work may advance widely used scales, and specified seven methodological recommendations for future resilience scale development with existing and new scales in and beyond the Chinese study contexts. We further addressed issues and challenges in measuring resilience as a process and called on researchers to further develop/evaluate process measures for Chinese-speaking populations.

Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology.

Age is a major risk factor for severe coronavirus disease 2019 (COVID-19), yet the mechanisms behind this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host immune response in the blood and the upper airway, as well as the nasal microbiome in a prospective, multicenter cohort of 1031 vaccine-naïve patients hospitalized for COVID-19 between 18 and 96 years old. We performed mass cytometry, serum protein profiling, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays, and blood and nasal transcriptomics. We found that older age correlated with increased SARS-CoV-2 viral abundance upon hospital admission, delayed viral clearance, and increased type I interferon gene expression in both the blood and upper airway. We also observed age-dependent up-regulation of innate immune signaling pathways and down-regulation of adaptive immune signaling pathways. Older adults had lower naïve T and B cell populations and higher monocyte populations. Over time, older adults demonstrated a sustained induction of pro-inflammatory genes and serum chemokines compared with younger individuals, suggesting an age-dependent impairment in inflammation resolution. Transcriptional and protein biomarkers of disease severity differed with age, with the oldest adults exhibiting greater expression of pro-inflammatory genes and proteins in severe disease. Together, our study finds that aging is associated with impaired viral clearance, dysregulated immune signaling, and persistent and potentially pathologic activation of pro-inflammatory genes and proteins.

Activated sputum eosinophils associated with exacerbations in children on mepolizumab.

BACKGROUND: MUPPITS-2 was a randomized, placebo-controlled clinical trial that demonstrated mepolizumab (anti-IL-5) reduced exacerbations and blood and airway eosinophils in urban children with severe eosinophilic asthma. Despite this reduction in eosinophilia, exacerbation risk persisted in certain patients treated with mepolizumab. This raises the possibility that subpopulations of airway eosinophils exist that contribute to breakthrough exacerbations. OBJECTIVE: We aimed to determine the effect of mepolizumab on airway eosinophils in childhood asthma. METHODS: Sputum samples were obtained from 53 MUPPITS-2 participants. Airway eosinophils were characterized using mass cytometry and grouped into subpopulations using unsupervised clustering analyses of 38 surface and intracellular markers. Differences in frequency and immunophenotype of sputum eosinophil subpopulations were assessed based on treatment arm and frequency of exacerbations. RESULTS: Median sputum eosinophils were significantly lower among participants treated with mepolizumab compared with placebo (58% lower, 0.35% difference [95% CI 0.01, 0.74], P = .04). Clustering analysis identified 3 subpopulations of sputum eosinophils with varied expression of CD62L. CD62Lint and CD62Lhi eosinophils exhibited significantly elevated activation marker and eosinophil peroxidase expression, respectively. In mepolizumab-treated participants, CD62Lint and CD62Lhi eosinophils were more abundant in participants who experienced exacerbations than in those who did not (100% higher for CD62Lint, 0.04% difference [95% CI 0.0, 0.13], P = .04; 93% higher for CD62Lhi, 0.21% difference [95% CI 0.0, 0.77], P = .04). CONCLUSIONS: Children with eosinophilic asthma treated with mepolizumab had significantly lower sputum eosinophils. However, CD62Lint and CD62Lhi eosinophils were significantly elevated in children on mepolizumab who had exacerbations, suggesting that eosinophil subpopulations exist that contribute to exacerbations despite anti-IL-5 treatment.

A comparison of the epidemiology of kidney replacement therapy between Europe and the United States: 2021 data of the ERA Registry and the USRDS.

BACKGROUND AND HYPOTHESIS: This paper compares the most recent data on the incidence and prevalence of kidney replacement therapy (KRT), kidney transplantation rates, and mortality on KRT from Europe to those from the United States (US), including comparisons of treatment modalities (haemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KTx)). METHODS: Data were derived from the annual reports of the European Renal Association (ERA) Registry and the United States Renal Data System (USRDS). The European data include information from national and regional renal registries providing the ERA Registry with individual patient data. Additional analyses were performed to present results for all participating European countries together. RESULTS: In 2021, the KRT incidence in the US (409.7 per million population (pmp)) was almost 3-fold higher than in Europe (144.4 pmp). Despite the substantial difference in KRT incidence, approximately the same proportion of patients initiated HD (Europe: 82%, US: 84%), PD (14%; 13% respectively), or underwent pre-emptive KTx (4%; 3% respectively). The KRT prevalence in the US (2436.1 pmp) was 2-fold higher than in Europe (1187.8 pmp). Within Europe, approximately half of all prevalent patients were living with a functioning graft (47%), while in the US, this was one third (32%). The number of kidney transplantations performed was almost twice as high in the US (77.0 pmp) compared to Europe (41.6 pmp). The mortality of patients receiving KRT was 1.6-fold higher in the US (157.3 per 1000 patient years) compared to Europe (98.7 per 1000 patient years). CONCLUSIONS: The US had a much higher KRT incidence, prevalence, and mortality compared to Europe, and despite a higher kidney transplantation rate, a lower proportion of prevalent patients with a functioning graft.

Host-Microbe Multiomic Profiling Reveals Age-Dependent COVID-19 Immunopathology.

Age is a major risk factor for severe coronavirus disease-2019 (COVID-19), yet the mechanisms responsible for this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host and viral dynamics in a prospective, multicenter cohort of 1,031 patients hospitalized for COVID-19, ranging from 18 to 96 years of age. We performed blood transcriptomics and nasal metatranscriptomics, and measured peripheral blood immune cell populations, inflammatory protein expression, anti-SARS-CoV-2 antibodies, and anti-interferon (IFN) autoantibodies. We found that older age correlated with an increased SARS-CoV-2 viral load at the time of admission, and with delayed viral clearance over 28 days. This contributed to an age-dependent increase in type I IFN gene expression in both the respiratory tract and blood. We also observed age-dependent transcriptional increases in peripheral blood IFN-γ, neutrophil degranulation, and Toll like receptor (TLR) signaling pathways, and decreases in T cell receptor (TCR) and B cell receptor signaling pathways. Over time, older adults exhibited a remarkably sustained induction of proinflammatory genes (e.g., CXCL6) and serum chemokines (e.g., CXCL9) compared to younger individuals, highlighting a striking age-dependent impairment in inflammation resolution. Augmented inflammatory signaling also involved the upper airway, where aging was associated with upregulation of TLR, IL17, type I IFN and IL1 pathways, and downregulation TCR and PD-1 signaling pathways. Metatranscriptomics revealed that the oldest adults exhibited disproportionate reactivation of herpes simplex virus and cytomegalovirus in the upper airway following hospitalization. Mass cytometry demonstrated that aging correlated with reduced naïve T and B cell populations, and increased monocytes and exhausted natural killer cells. Transcriptional and protein biomarkers of disease severity markedly differed with age, with the oldest adults exhibiting greater expression of TLR and inflammasome signaling genes, as well as proinflammatory proteins (e.g., IL6, CXCL8), in severe COVID-19 compared to mild/moderate disease. Anti-IFN autoantibody prevalence correlated with both age and disease severity. Taken together, this work profiles both host and microbe in the blood and airway to provide fresh insights into aging-related immune changes in a large cohort of vaccine-naïve COVID-19 patients. We observed age-dependent immune dysregulation at the transcriptional, protein and cellular levels, manifesting in an imbalance of inflammatory responses over the course of hospitalization, and suggesting potential new therapeutic targets.

"Not just rebellious, it's revolutionary": Do-it-yourself hormone replacement therapy as Liberatory Harm Reduction.

For some transgender people, hormone replacement therapy (HRT) is "an ontological necessity for a livable life" (Fondén, 2020, p. 29). Some trans people engage in do-it-yourself (DIY) HRT (aka "DIYers") because of care barriers, including medication costs, difficulty accessing healthcare providers, and mistrust in professionalized medical systems. Although DIY HRT is often framed as highly risky, we analyzed in-depth interviews with 36 U.S. DIYers to understand how they themselves perceived their goals, challenges, and risk mitigation using the Liberatory Harm Reduction and lay expertise frameworks. Participants emphasized experiences of transphobia within medical spaces. In contrast, participants characterized DIY HRT as a community-driven, accessible, and empowering practice. Through self-organized online forums and mutual aid, DIYers constructed adaptive health-promoting practices that challenge biomedical conceptualizations of risk and affirm trans agency.

Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop.

Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes the major points and conclusions from this NIAID workshop. As a group, the investigators underscored the imperatives for rigorous analytic frameworks, integration of different omics data types, cross-disciplinary interaction, strategies for overcoming current limitations, and the overarching goal to improve scientific understanding and care of asthma and allergic diseases.

Spatial Vision Inequalities: A Literature Review of the Impact of Place on Vision and Eye Health Outcomes.

"Neighborhood and built environment" is one of the five domains of social determinants of health that has been outlined by Healthy People 2030, and this domain impacts an individual's well-being, health, and quality of life. Social risk factors (SRFs) in the neighborhood and built environment domain include unstable or unsafe housing, poor access to transportation, lack of green spaces, pollution, safety concerns, and neighborhood measures of inequity. In this narrative literature review, we assess the relationship between neighborhood and built environment SRFs and eye health and vision outcomes. We explain how mapping neighborhood-level SRFs may be used to advance health equity in the field of eye health and vision care.

Relationship between Unstable Housing, Food Insecurity, and Vision Status in the MI-SIGHT Community Eye Disease Screening Program.

PURPOSE: Assess rate of visual impairment (VI) from uncorrected refractive error (URE) and associations with demographic and socioeconomic factors among low-income patients presenting to the Michigan Screening and Intervention for Glaucoma and Eye Health through Telemedicine (MI-SIGHT) program. DESIGN: Cross-sectional study. PARTICIPANTS: Adults ≥ 18 years without acute ocular symptoms. METHODS: MI-SIGHT program participants received a telemedicine-based eye disease screening and ordered glasses through an online optical shop. Participants were categorized based on refractive error (RE) status: VI from URE (presenting visual acuity [PVA] ≤ 20/50, best corrected visual acuity [BCVA] ≥ 20/40), URE without VI (PVA ≥ 20/40, had ≥ 2 lines of improvement to BCVA), and no or adequately corrected RE (PVA ≥ 20/40, < 2 line improvement to BCVA). Patient demographics, self-reported visual function, and satisfaction with glasses obtained through the program were compared between groups using analysis of variance, Kruskal-Wallis, chi-square, and Fisher exact testing. MAIN OUTCOME MEASURES: PVA, BCVA, and presence of VI (defined as PVA ≤ 20/50). RESULTS: Of 1171 participants enrolled in the MI-SIGHT program during the first year, the average age was 55.1 years (standard deviation = 14.5), 37.7% were male, 54.1% identified as Black, and 1166 (99.6%) had both PVA and BCVA measured. VI was observed in 120 (10.3%); 96 had VI from URE (8.2%), 168 (14.4%) had URE without VI, and 878 (75.3%) had no or adequately corrected RE. A smaller percentage of participants with VI from URE reported having a college degree and a larger percentage reported income < $10 000 compared to participants with no or adequately corrected RE (3.2% versus 14.2%, P = 0.02; 45.5% versus 21.6%, respectively, P < 0.0001. Visual function was lowest among participants with VI from URE, followed by those with URE without VI, and then those with no or adequately corrected RE (VFQ9 composite score 67.3 ± 19.6 versus 77.0 ± 14.4 versus 82.2 ± 13.3, respectively; P < 0.0001). 71.2% (n = 830) ordered glasses for an average cost of $36.80 ± $32.60; 97.7% were satisfied with their glasses. CONCLUSIONS: URE was the main cause of VI at 2 clinics serving low-income communities and was associated with reduced vision-related quality of life. An online optical shop with lower prices made eyeglasses accessible to low-income patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Enhancing Immunogenicity of a Thermostable, Efficacious SARS-CoV-2 Vaccine Formulation through Oligomerization and Adjuvant Choice.

Currently deployed SARS-CoV-2 vaccines all require storage at refrigerated or sub-zero temperatures. We demonstrate that after month-long incubation at 37 °C, solubilization, and formulation with squalene-in-water emulsion adjuvant, a stabilized receptor binding domain retains immunogenicity and protective efficacy. We also examine the effects of trimerization of the stabilized RBD, as well as of additional adjuvants, on both B and T-cell responses. The additional emulsion or liposome-based adjuvants contained a synthetic TLR-4 ligand and/or the saponin QS-21. Trimerization enhanced immunogenicity, with significant antibody titers detectable after a single immunization. Saponin-containing adjuvants elicited enhanced immunogenicity relative to both emulsion and aluminum hydroxide adjuvanted formulations lacking these immunostimulants. Trimeric RBD formulated with liposomal based adjuvant containing both TLR-4 ligand and saponin elicited a strongly Th1 biased response, with ~10-fold higher neutralization titers than the corresponding aluminum hydroxide adjuvanted formulation. The SARS-CoV-2 virus is now endemic in humans, and it is likely that periodic updating of vaccine formulations in response to viral evolution will continue to be required to protect vulnerable individuals. In this context, it is desirable to have efficacious, thermostable vaccine formulations to facilitate widespread vaccine coverage, including in low- and middle-income countries, where global access rights to clinically de-risked adjuvants will be important moving forward.

Emulsion and liposome-based adjuvanted R21 vaccine formulations mediate protection against malaria through distinct immune mechanisms.

Adjuvanted protein vaccines offer high efficacy, yet most potent adjuvants remain proprietary. Several adjuvant compounds are being developed by the Vaccine Formulation Institute in Switzerland for global open access clinical use. In the context of the R21 malaria vaccine, in a mouse challenge model, we characterize the efficacy and mechanism of action of four Vaccine Formulation Institute adjuvants: two liposomal (LQ and LMQ) and two squalene emulsion-based adjuvants (SQ and SMQ), containing QS-21 saponin (Q) and optionally a synthetic TLR4 agonist (M). Two R21 vaccine formulations, R21/LMQ and R21/SQ, offer the highest protection (81%-100%), yet they trigger different innate sensing mechanisms in macrophages with LMQ, but not SQ, activating the NLRP3 inflammasome. The resulting in vivo adaptive responses have a different TH1/TH2 balance and engage divergent innate pathways while retaining high protective efficacy. We describe how modular changes in vaccine formulation allow for the dissection of the underlying immune pathways, enabling future mechanistically informed vaccine design.

Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants.

Hospitalized COVID-19 patients exhibit diverse clinical outcomes, with some individuals diverging over time even though their initial disease severity appears similar. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity. In this study, we carried out deep immunophenotyping and conducted longitudinal multi-omics modeling integrating ten distinct assays on a total of 1,152 IMPACC participants and identified several immune cascades that were significant drivers of differential clinical outcomes. Increasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, NETosis, and T-cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma immunoglobulins and B cells, as well as dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to the failure of viral clearance in patients with fatal illness. Our longitudinal multi-omics profiling study revealed novel temporal coordination across diverse omics that potentially explain disease progression, providing insights that inform the targeted development of therapies for hospitalized COVID-19 patients, especially those critically ill.

Relationship of Heterologous Virus Responses and Outcomes in Hospitalized COVID-19 Patients.

The clinical trajectory of COVID-19 may be influenced by previous responses to heterologous viruses. We examined the relationship of Abs against different viruses to clinical trajectory groups from the National Institutes of Health IMPACC (Immunophenotyping Assessment in a COVID-19 Cohort) study of hospitalized COVID-19 patients. Whereas initial Ab titers to SARS-CoV-2 tended to be higher with increasing severity (excluding fatal disease), those to seasonal coronaviruses trended in the opposite direction. Initial Ab titers to influenza and parainfluenza viruses also tended to be lower with increasing severity. However, no significant relationship was observed for Abs to other viruses, including measles, CMV, EBV, and respiratory syncytial virus. We hypothesize that some individuals may produce lower or less durable Ab responses to respiratory viruses generally (reflected in lower baseline titers in our study), and that this may carry over into poorer outcomes for COVID-19 (despite high initial SARS-CoV-2 titers). We further looked at longitudinal changes in Ab responses to heterologous viruses, but found little change during the course of acute COVID-19 infection. We saw significant trends with age for Ab levels to many of these viruses, but no difference in longitudinal SARS-CoV-2 titers for those with high versus low seasonal coronavirus titers. We detected no difference in longitudinal SARS-CoV-2 titers for CMV seropositive versus seronegative patients, although there was an overrepresentation of CMV seropositives among the IMPACC cohort, compared with expected frequencies in the United States population. Our results both reinforce findings from other studies and suggest (to our knowledge) new relationships between the response to SARS-CoV-2 and Abs to heterologous viruses.

Assessing Communicative Resilience in Suicide Prevention for LGBTQ+ Communities: A Qualitative Analysis of Community Conversations.

PURPOSE: Since LGBTQ + communities experience disproportionate rates of suicidality; it is important to identify strategies for suicide prevention. Research shows that supportive interpersonal communication and identity affirmation helps prevent suicide. The purpose of this analysis is to explore the role of communicative resilience in suicide prevention among LGBTQ + communities. APPROACH: This analysis is part of a community-based participatory research project. SETTING: In November 2021, a Community-Academic Partnership hosted a virtual town hall, via Zoom, immediately followed by five Community Conversation (CC) groups. PARTICIPANTS: Participants were aged 18 years or older and identified as an LGBTQ + community member or active ally. We define active ally as an individual who, through their personal relationships, service to the community, or professional work, actively advocates for and supports members of LGBTQ + communities. METHOD: CC groups were audio-recorded and transcribed (n= 25 participants). Transcripts were inductively coded for thematic analysis and identified themes were deductively coded using Communication Theory of Resilience (CTR) to identify observations of communicative resilience (MaxQDA2020). RESULTS: Themes aligned with CTR, including importance of peer and professional support, affirming identities, reducing stigma, cultivating hope, and advocating for equitable policies. CONCLUSION: Findings demonstrate that through communication, members of LGBTQ + communities enact processes of resilience that support and promote suicide prevention. These findings support community mobilization, communicative resilience, and advocacy to help save lives.