Browsing by Author "Yu, Chen"
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Item Open Access Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.(Nature communications, 2021-02-17) McClain, Micah T; Constantine, Florica J; Henao, Ricardo; Liu, Yiling; Tsalik, Ephraim L; Burke, Thomas W; Steinbrink, Julie M; Petzold, Elizabeth; Nicholson, Bradly P; Rolfe, Robert; Kraft, Bryan D; Kelly, Matthew S; Saban, Daniel R; Yu, Chen; Shen, Xiling; Ko, Emily M; Sempowski, Gregory D; Denny, Thomas N; Ginsburg, Geoffrey S; Woods, Christopher WSARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral blood samples from 46 subjects with COVID-19 and directly comparing them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a powerful transcriptomic response in peripheral blood with conserved components that are heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, which persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95 [95% CI 0.92-0.98]). The transcriptome in peripheral blood reveals both diverse and conserved components of the immune response in COVID-19 and provides for potential biomarker-based approaches to diagnosis.Item Open Access Healthcare utilization and costs associated with dabigatran compared to warfarin treatment in newly diagnosed patients with non-valvular atrial fibrillation.(Current medical research and opinion, 2015-12) Francis, Kevin; Yu, Chen; Alvrtsyan, Hasmik; Sander, Stephen; Ghosh, Sabyasachi; Rao, Yajing; Sanchez, Herman; Matchar, DavidPurpose
Real-world healthcare resource utilization and costs were compared among patients with non-valvular atrial fibrillation (NVAF) receiving either dabigatran or warfarin.Methods
A retrospective cohort study was conducted using administrative claims data from the United States Department of Defense (DOD) Military Health System. Patients with newly diagnosed AF initiated on dabigatran or warfarin were identified using ICD-9 diagnosis, procedure and drug codes. Patients were observed for 3 months prior to treatment initiation to ascertain a diagnosis of valvular heart disease and 12 months for exclusion of those with a history of anticoagulation therapy. Propensity score matching was used to balance baseline characteristics between the two treatment cohorts. Medical and pharmacy utilization and costs were compared between the dabigatran and warfarin treatment groups for 3 and 12 months following treatment initiation.Results
A total of 1102 patients with newly diagnosed NVAF initiated on dabigatran were matched with corresponding warfarin-treated patients. In the 12 months following initiation of anticoagulation, the mean medical costs for patients initiated on dabigatran were significantly lower than for patients initiated on warfarin (-$6299, p < 0.001), largely due to fewer hospitalizations (-0.162, p = 0.009). While pharmacy costs were higher ($4369, p < 0.001) for dabigatran, overall healthcare costs were significantly lower compared with patients on warfarin (12 months: -$1940, p < 0.001). Mean hospital length of stay between these two groups were similar (6.033 days for dabigatran vs 6.318 days for warfarin, p = 0.139).Conclusion
Despite higher pharmacy costs for NVAF patients initiated on dabigatran vs warfarin, this was more than offset by lower utilization of medical care resources.Item Open Access Higher persistence in newly diagnosed nonvalvular atrial fibrillation patients treated with dabigatran versus warfarin.(Circulation. Cardiovascular quality and outcomes, 2013-09) Zalesak, Martin; Siu, Kimberly; Francis, Kevin; Yu, Chen; Alvrtsyan, Hasmik; Rao, Yajing; Walker, David; Sander, Stephen; Miyasato, Gavin; Matchar, David; Sanchez, HermanBackground
Oral anticoagulation therapy is the primary tool in reducing stroke risk in patients with nonvalvular atrial fibrillation but is underused. Patients nonpersistent with therapy contribute to this underuse. The objective of this study was to compare persistence rates in newly diagnosed nonvalvular atrial fibrillation patients treated with warfarin versus dabigatran as their oral anticoagulation.Methods and results
US Department of Defense administrative claims were used to identify patients receiving warfarin or dabigatran between October 28, 2010, and June 30, 2012. Patient records were examined for a minimum of 12 months before index date to restrict the analyses to those newly diagnosed with nonvalvular atrial fibrillation and naive-to-treatment, identifying 1775 on warfarin and 3370 on dabigatran. Propensity score matching was used to identify 1745 matched pairs. Persistence was defined as time on therapy to discontinuation. Kaplan-Meier curves were used to depict persistence over time. Cox proportional hazards model was used to determine the factors significantly associated with persistence. Using a 60-day permissible medication gap, the persistence rates were higher for dabigatran than for warfarin at both 6 months (72% versus 53%) and 1 year (63% versus 39%). Patients on dabigatran with a low-to-moderate risk of stroke (CHADS2<2) or with a higher bleed risk (HEMORR2HAGES>3) had a higher likelihood of nonpersistence (hazard ratios, 1.37; 95% confidence interval, 1.17-1.60; P<0.001; and hazard ratios, 1.24; 95% confidence interval, 1.04-1.47; P=0.016).Conclusions
Patients who initiated dabigatran treatment were more persistent than patients who began warfarin treatment. Within each cohort, patients with lower stroke risk were more likely to discontinue therapy.Item Open Access Mucosal Associated Invariant T (MAIT) Cell Responses Differ by Sex in COVID-19.(Med (New York, N.Y.), 2021-04-13) Yu, Chen; Littleton, Sejiro; Giroux, Nicholas S; Mathew, Rose; Ding, Shengli; Kalnitsky, Joan; Yang, Yuchen; Petzold, Elizabeth; Chung, Hong A; Rivera, Grecia O; Rotstein, Tomer; Xi, Rui; Ko, Emily R; Tsalik, Ephraim L; Sempowski, Gregory D; Denny, Thomas N; Burke, Thomas W; McClain, Micah T; Woods, Christopher W; Shen, Xiling; Saban, Daniel RSexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, yet the mechanisms governing this disparity remain incompletely understood. We carried out sex-balanced sampling of peripheral blood mononuclear cells from confirmed COVID-19 inpatients and outpatients, uninfected close contacts, and healthy controls for 36-color flow cytometry and single cell RNA-sequencing. Our results revealed a pronounced reduction of circulating mucosal associated invariant T (MAIT) cells in infected females. Integration of published COVID-19 airway tissue datasets implicate that this reduction represented a major wave of MAIT cell extravasation during early infection in females. Moreover, female MAIT cells possessed an immunologically active gene signature, whereas male counterparts were pro-apoptotic. Collectively, our findings uncover a female-specific protective MAIT profile, potentially shedding light on reduced COVID-19 susceptibility in females.