Project description:Analysis of steady-state mRNA levels in trisomy 21 subjects ± clonal hematopoiesis. This dataset is part of the Human Trisome Project run by the Linda Crnic Institute for Down Syndrome at the University of Colorado Anschutz Medical Campus. http://www.trisome.org/
Project description:Analysis of steady-state mRNA levels in whole blood of euploid controls and subjects with trisomy 21. This dataset is part of the Human Trisome Project run by the Linda Crnic Institute for Down Syndrome at the University of Colorado Anschutz Medical Campus. http://www.trisome.org/
Project description:Vaccine Hesitancy (VH) is a relevant obstacle for the COVID-19 vaccination campaign. The aim of this study is to assess the proportion of subjects unwilling to vaccinate among patients with type 1 (T1DM) and 2 (T2DM) diabetes, exploring factors associated with VH. A purposely created interview was delivered from physicians to a consecutive series of adult (>18 years) subjects with diabetes referring to the Diabetes Outpatient Clinic of Careggi Hospital, Florence, from January 1st to April 30th 2021. Out of 502 subjects enrolled, 92 were vaccine hesitant respondents (18.3%); the corresponding figure for T1DM and T2DM was 13.0% (N = 14), and 19.9% (N = 78), respectively. After adjusting for age, higher HbA1c (1.07 [1.02-1.13], p = 0.008) and triglycerides levels (1.03 [1.01-1.06], p = 0.011) were positively associated with VH, among patients with T1DM. At multivariate analysis, after adjusting for age, creatinine, and statin use, patients with T2DM affected by obesity (9.98 [4.89-9.59], p < 0.01) and with lower levels of creatinine (0.36 [0.21-0.54], p = 0.029) were more likely to refuse COVID vaccination. Hesitancy toward COVID-19 vaccination among subjects with diabetes is not negligible and seems to be more prevalent in individuals with lower adherence to medical prescriptions and/or reduced concerns over their health. This suggests the need for specific interventions to increase awareness and counter prejudices on vaccines.
Project description:Despite tremendous efforts by the international research community to understand the pathophysiology of SARS-CoV-2 infection, the reasons behind the clinical variability, ranging from asymptomatic infection to lethal disease, are still unclear. Existing inter-individual variations of the immune responses, due to environmental exposures and genetic factors, may be critical to the development or not of symptomatic disease after infection with SARS-CoV-2, and transcriptomic differences marking such responses may be observed even later, after convalescence. Herein, we performed genome-wide transcriptional whole-blood profiling to test the hypothesis that immune response-related gene signatures may differ between healthy individuals with prior entirely asymptomatic versus clinical SARS-CoV-2 infection, all of which developed an equally robust antibody response. Among 12.789 protein-coding genes analyzed, there were only six and nine genes with significantly decreased or increased expression, respectively, in those with prior asymptomatic infection (n=17, mean age 34 years) relatively to those with clinical infection (n=15, mean age 37 years). All six genes with decreased expression (IFIT3, IFI44L, RSAD2, FOLR3, PI3, ALOX15), are involved in innate immune response while the first two are interferon-induced proteins. Among genes with increased expression six are involved in immune response (GZMH, CLEC1B, CLEC12A), viral mRNA translation (GCAT), energy metabolism (CACNA2D2) and oxidative stress response (ENC1). Notably, 8/15 differentially expressed genes are regulated by interferons. Our results suggest that an intrinsically weaker expression of some innate immunityrelated genes may be associated with an asymptomatic disease course in SARS-CoV-2 infection. Whether a certain gene signature predicts, or not, those who will develop a more efficient immune response upon exposure to SARS-CoV-2, with implications for prioritization for vaccination, warrant further study.
Project description:Analysis of steady-state mRNA levels in whole blood of subjects with Down syndrome (trisomy 21) and qualifying moderate-to-severe immune skin conditions. This dataset is part of the Human Trisome Project run by the Linda Crnic Institute for Down Syndrome at the University of Colorado Anschutz Medical Campus. http://www.trisome.org/
Project description:There is a critical need for safe and effective drugs for COVID-19. Only remdesivir has received authorization for COVID-19 and has been shown to improve outcomes but not decrease mortality. However, the dose of remdesivir is limited by hepatic and kidney toxicity. ACE2 is the critical cell surface receptor for SARS-CoV-2. Here, we investigated additive effect of combination therapy using remdesivir with recombinant soluble ACE2 (high/low dose) on Vero E6 and kidney organoids, targeting two different modalities of SARS-CoV-2 life cycle: cell entry via its receptor ACE2 and intracellular viral RNA replication. This combination treatment markedly improved their therapeutic windows against SARS-CoV-2 in both models. By using single amino-acid resolution screening in haploid ES cells, we report a singular critical pathway required for remdesivir toxicity, namely Adenylate Kinase 2. The data provided here demonstrate that combining two therapeutic modalities with different targets, common strategy in HIV treatment, exhibit strong additive effects at sub-toxic concentrations. Our data lay the groundwork for the study of combinatorial regimens in future COVID-19 clinical trials.
Project description:IntroductionThe endothelial protein C receptor (EPCR) is a protein that regulates the protein C anticoagulant and anti-inflammatory pathways. A soluble form of EPCR (sEPCR) circulates in plasma and inhibits activated protein C (APC) activities. The clinical impact of sEPCR and its involvement in COVID-19 has not been explored. In this study, we investigated whether sEPCR levels were related to COVID-19 patients' requirement for hospitalization.MethodsPlasma sEPCR levels were measured on hospital admission in 84 COVID-19 patients, and in 11 non-hospitalized SARS-CoV2-positive patients approximately 6 days after reported manifestation of their symptoms. Multiple logistic regression analysis was performed to identify potential risk factors for hospitalization and receiver operating characteristic (ROC) curves were generated to assess their value.ResultsIn our cohort, hospitalized patients had considerably higher sEPCR levels upon admission compared with outpatients [107.5 (76.7-156.3) vs. 44.6 (12.1-84.4) ng/mL; P < 0.0001)]. The ROC curve using hospitalization as the classification variable and sEPCR levels as the prognostic variable generated an area under the curve at 0.845 (95% CI = 0.710-0.981, P < 0.001). Additionally, we investigated the predictive value of sEPCR combined with BMI, age, or D-dimers.ConclusionsIn our cohort, sEPCR levels in COVID-19 patients upon hospital admission appear considerably elevated compared with outpatients; this could lead to impaired APC activities and might contribute to the pro-coagulant phenotype reported in such patients. sEPCR measurement might be useful as a point-of-care test in SARS-CoV2-positive patients.