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Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.
Abby Lee; Grant Castaneda; Wei Li; Chengyu Chen; Neil Shende; Jaideep Chakladar; Pam Taub; Eric Chang; Weg Ongkeko. COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation. Viruses 2021, 13, 1018 .
AMA StyleAbby Lee, Grant Castaneda, Wei Li, Chengyu Chen, Neil Shende, Jaideep Chakladar, Pam Taub, Eric Chang, Weg Ongkeko. COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation. Viruses. 2021; 13 (6):1018.
Chicago/Turabian StyleAbby Lee; Grant Castaneda; Wei Li; Chengyu Chen; Neil Shende; Jaideep Chakladar; Pam Taub; Eric Chang; Weg Ongkeko. 2021. "COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation." Viruses 13, no. 6: 1018.
The intra-tumor microbiota has been increasingly implicated in cancer pathogenesis. In this study, we aimed to examine the microbiome in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and determine its compositional differences with relation to age and gender. After grouping 497 LUAD and 433 LUSC patients by age and gender and removing potential contaminants, we identified differentially abundant microbes in each patient cohort vs. adjacent normal samples. We then correlated dysregulated microbes with patient survival rates, immune infiltration, immune and cancer pathways, and genomic alterations. We found that most age and gender cohorts in both LUAD and LUSC contained unique, significantly dysregulated microbes. For example, LUAD-associated Escherichia coli str. K-12 substr. W3110 was dysregulated in older female and male patients and correlated with both patient survival and genomic alterations. For LUSC, the most prominent bacterial species that we identified was Pseudomonas putida str. KT2440, which was uniquely associated with young LUSC male patients and immune infiltration. In conclusion, we found differentially abundant microbes implicated with age and gender that are also associated with genomic alterations and immune dysregulations. Further investigation should be conducted to determine the relationship between gender and age-associated microbes and the pathogenesis of lung cancer.
Lindsay M. Wong; Neil Shende; Wei Tse Li; Grant Castaneda; Lauren Apostol; Eric Y. Chang; Weg M. Ongkeko. Comparative Analysis of Age- and Gender-Associated Microbiome in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma. Cancers 2020, 12, 1447 .
AMA StyleLindsay M. Wong, Neil Shende, Wei Tse Li, Grant Castaneda, Lauren Apostol, Eric Y. Chang, Weg M. Ongkeko. Comparative Analysis of Age- and Gender-Associated Microbiome in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma. Cancers. 2020; 12 (6):1447.
Chicago/Turabian StyleLindsay M. Wong; Neil Shende; Wei Tse Li; Grant Castaneda; Lauren Apostol; Eric Y. Chang; Weg M. Ongkeko. 2020. "Comparative Analysis of Age- and Gender-Associated Microbiome in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma." Cancers 12, no. 6: 1447.
The COVID-19 pandemic is marked by a wide range of clinical disease courses, ranging from asymptomatic to deadly. There have been many studies seeking to explore the correlations between COVID-19 clinical outcomes and various clinical variables, including age, sex, race, underlying medical problems, and social habits. In particular, the relationship between smoking and COVID-19 outcome is controversial, with multiple conflicting reports in the current literature. In this study, we aim to analyze how smoking may affect the SARS-CoV-2 infection rate. We analyzed sequencing data from lung and oral epithelial samples obtained from The Cancer Genome Atlas (TCGA). We found that the receptor and transmembrane protease necessary for SARS-CoV-2 entry into host cells, ACE2 and TMPRSS2, respectively, were upregulated in smoking samples from both lung and oral epithelial tissue. We then explored the mechanistic hypothesis that smoking may upregulate ACE2 expression through the upregulation of the androgen pathway. ACE2 and TMPRSS2 upregulation were both correlated to androgen pathway enrichment and the specific upregulation of central pathway regulatory genes. These data provide a potential model for the increased susceptibility of smoking patients to COVID-19 and encourage further exploration into the androgen and tobacco upregulation of ACE2 to understand the potential clinical ramifications.
Jaideep Chakladar; Neil Shende; Wei Tse Li; Mahadevan Rajasekaran; Eric Y. Chang; Weg M. Ongkeko. Smoking-Mediated Upregulation of the Androgen Pathway Leads to Increased SARS-CoV-2 Susceptibility. International Journal of Molecular Sciences 2020, 21, 3627 .
AMA StyleJaideep Chakladar, Neil Shende, Wei Tse Li, Mahadevan Rajasekaran, Eric Y. Chang, Weg M. Ongkeko. Smoking-Mediated Upregulation of the Androgen Pathway Leads to Increased SARS-CoV-2 Susceptibility. International Journal of Molecular Sciences. 2020; 21 (10):3627.
Chicago/Turabian StyleJaideep Chakladar; Neil Shende; Wei Tse Li; Mahadevan Rajasekaran; Eric Y. Chang; Weg M. Ongkeko. 2020. "Smoking-Mediated Upregulation of the Androgen Pathway Leads to Increased SARS-CoV-2 Susceptibility." International Journal of Molecular Sciences 21, no. 10: 3627.