5 research outputs found
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Resistin-Like Molecule Alpha Lentivirus and Utilizing Community Engaged Research to Tackle COVID-19 Health Disparities
Macrophage-derived proteins play critical roles throughout all stages of the immune response to a variety of pathogens. Depending on the immunological challenge and the subsequent cytokines produced in response, macrophages will become classically (IFNγ) or alternatively activated (IL-4), with an entire spectrum of macrophage phenotypes existing between these two classifications. Upon activation, macrophages will produce a diverse array of proteins and cytokines to guide the immune response depending on the stimulus. Resistin-like molecule alpha (RELMα) is an example of such a protein that is secreted by alternatively activated M2-macrophages. Our laboratory has previously identified a variety of roles for RELMα in vivo and in vitro. However, knowledge gaps remain with regards to potential cell-extrinsic versus cell-intrinsic differences of immune regulating proteins on cell behavior and function. These include whether there is a difference in how a cell behaves when it expresses the protein or whether it encounters it extracellularly, or whether the function differs dependent on the cell-type, given that RELM is expressed by immune and non-immune cells. To begin addressing these questions, new tools are needed that allow overexpression in cell lines and primary cells. In the first part of this thesis, I sought to generate a RELMα over-expressing lentivirus to be later utilized in the efficient transduction of both cell lines and primary cells.Community-based research has the potential to improve the possibility of reducing certain health disparities. The COVID-19 pandemic brought health disparities to the forefront, many of which existed before and were exacerbated by it. It then becomes the responsibility of researchers to engage within a community-based framework to use these opportunities and address the factors driving these disparities. Research conducted at the UC Riverside School of Medicine on COVID-19 in Riverside County has identified such disparities in the population, where Hispanic individuals were more likely to be severely infected with COVID-19. When opportunity arises in which community-engaged research should be performed, we offer the methodology and framework that was used in planning for our community-engaged research symposium that fostered a rich environment of academic and community collaboration. In the second part of my thesis, I will go into the community-engaged research I performed that allowed for the successful execution of a community-focused COVID-19 symposium
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Health disparities in COVID-19: immune and vascular changes are linked to disease severity and persist in a high-risk population in Riverside County, California
BackgroundHealth disparities in underserved communities, such as inadequate healthcare access, impact COVID-19 disease outcomes. These disparities are evident in Hispanic populations nationwide, with disproportionately high infection and mortality rates. Furthermore, infected individuals can develop long COVID with sustained impacts on quality of life. The goal of this study was to identify immune and endothelial factors that are associated with COVID-19 outcomes in Riverside County, a high-risk and predominantly Hispanic community, and investigate the long-term impacts of COVID-19 infection.Methods112 participants in Riverside County, California, were recruited according to the following criteria: healthy control (n = 23), outpatients with moderate infection (outpatient, n = 33), ICU patients with severe infection (hospitalized, n = 33), and individuals recovered from moderate infection (n = 23). Differences in outcomes between Hispanic and non-Hispanic individuals and presence/absence of co-morbidities were evaluated. Circulating immune and vascular biomarkers were measured by ELISA, multiplex analyte assays, and flow cytometry. Follow-up assessments for long COVID, lung health, and immune and vascular changes were conducted after recovery (n = 23) including paired analyses of the same participants.ResultsCompared to uninfected controls, the severe infection group had a higher proportion of Hispanic individuals (n = 23, p = 0.012) than moderate infection (n = 8, p = 0.550). Disease severity was associated with changes in innate monocytes and neutrophils, lymphopenia, disrupted cytokine production (increased IL-8 and IP-10/CXCL10 but reduced IFNλ2/3 and IFNγ), and increased endothelial injury (myoglobin, VCAM-1). In the severe infection group, a machine learning model identified LCN2/NGAL, IL-6, and monocyte activation as parameters associated with fatality while anti-coagulant therapy was associated with survival. Recovery from moderate COVID infection resulted in long-term immune changes including increased monocytes/lymphocytes and decreased neutrophils and endothelial markers. This group had a lower proportion of co-morbidities (n = 8, p = 1.0) but still reported symptoms associated with long COVID despite recovered pulmonary function.ConclusionThis study indicates increased severity of COVID-19 infection in Hispanic individuals of Riverside County, California. Infection resulted in immunological and vascular changes and long COVID symptoms that were sustained for up to 11 months, however, lung volume and airflow resistance was recovered. Given the immune and behavioral impacts of long COVID, the potential for increased susceptibility to infections and decreased quality of life in high-risk populations warrants further investigation
Health disparities in COVID-19: immune and vascular changes are linked to disease severity and persist in a high-risk population in Riverside County, California
Abstract Background Health disparities in underserved communities, such as inadequate healthcare access, impact COVID-19 disease outcomes. These disparities are evident in Hispanic populations nationwide, with disproportionately high infection and mortality rates. Furthermore, infected individuals can develop long COVID with sustained impacts on quality of life. The goal of this study was to identify immune and endothelial factors that are associated with COVID-19 outcomes in Riverside County, a high-risk and predominantly Hispanic community, and investigate the long-term impacts of COVID-19 infection. Methods 112 participants in Riverside County, California, were recruited according to the following criteria: healthy control (n = 23), outpatients with moderate infection (outpatient, n = 33), ICU patients with severe infection (hospitalized, n = 33), and individuals recovered from moderate infection (n = 23). Differences in outcomes between Hispanic and non-Hispanic individuals and presence/absence of co-morbidities were evaluated. Circulating immune and vascular biomarkers were measured by ELISA, multiplex analyte assays, and flow cytometry. Follow-up assessments for long COVID, lung health, and immune and vascular changes were conducted after recovery (n = 23) including paired analyses of the same participants. Results Compared to uninfected controls, the severe infection group had a higher proportion of Hispanic individuals (n = 23, p = 0.012) than moderate infection (n = 8, p = 0.550). Disease severity was associated with changes in innate monocytes and neutrophils, lymphopenia, disrupted cytokine production (increased IL-8 and IP-10/CXCL10 but reduced IFNλ2/3 and IFNγ), and increased endothelial injury (myoglobin, VCAM-1). In the severe infection group, a machine learning model identified LCN2/NGAL, IL-6, and monocyte activation as parameters associated with fatality while anti-coagulant therapy was associated with survival. Recovery from moderate COVID infection resulted in long-term immune changes including increased monocytes/lymphocytes and decreased neutrophils and endothelial markers. This group had a lower proportion of co-morbidities (n = 8, p = 1.0) but still reported symptoms associated with long COVID despite recovered pulmonary function. Conclusion This study indicates increased severity of COVID-19 infection in Hispanic individuals of Riverside County, California. Infection resulted in immunological and vascular changes and long COVID symptoms that were sustained for up to 11 months, however, lung volume and airflow resistance was recovered. Given the immune and behavioral impacts of long COVID, the potential for increased susceptibility to infections and decreased quality of life in high-risk populations warrants further investigation