Differential COVID-19 Symptoms Given Pandemic Locations, Time, and Comorbidities During the Early Pandemic.

BACKGROUND: COVID-19 pandemic is disaster to public health worldwide. Better perspective on COVID's features early in its course-prior to the development of vaccines and widespread variants-may prove useful in the understanding of future pandemics. Ontology provides a standardized integrative method for knowledge modeling and computer-assisted reasoning. In this study, we systematically extracted and analyzed clinical phenotypes and comorbidities in COVID-19 patients found at different countries and regions during the early pandemic using an ontology-based bioinformatics approach, with the aim to identify new insights and hidden patterns of the COVID-19 symptoms. RESULTS: A total of 48 research articles reporting analysis of first-hand clinical data from over 40,000 COVID-19 patients were surveyed. The patients studied therein were diagnosed with COVID-19 before May 2020. A total of 18 commonly-occurring phenotypes in these COVID-19 patients were first identified and then classified into different hierarchical groups based on the Human Phenotype Ontology (HPO). This meta-analytic approach revealed that fever, cough, and the loss of smell and taste were ranked as the most commonly-occurring phenotype in China, the US, and Italy, respectively. We also found that the patients from Europe and the US appeared to have more frequent occurrence of many nervous and abdominal symptom phenotypes (e.g., loss of smell, loss of taste, and diarrhea) than patients from China during the early pandemic. A total of 22 comorbidities, such as diabetes and kidney failure, were found to commonly exist in COVID-19 patients and positively correlated with the severity of the disease. The knowledge learned from the study was further modeled and represented in the Coronavirus Infectious Disease Ontology (CIDO), supporting semantic queries and analysis. Furthermore, also considering the symptoms caused by new viral variants at the later stages, a spiral model hypothesis was proposed to address the changes of specific symptoms during different stages of the pandemic. CONCLUSIONS: Differential patterns of symptoms in COVID-19 patients were found given different locations, time, and comorbidity types during the early pandemic. The ontology-based informatics provides a unique approach to systematically model, represent, and analyze COVID-19 symptoms, comorbidities, and the factors that influence the disease outcomes.

Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017.

This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers.

Acute increase in blood pressure during inhalation of coarse particulate matter air pollution from an urban location.

Particulate matter (PM) air pollution is a leading global risk factor for cardiovascular mortality. Although exposure to fine PM <2.5 µm raises arterial blood pressure (BP), few studies have evaluated the impact of coarse PM which differs in size (2.5-10 µm), sources, and chemistry. Twenty-nine healthy adults (30.4 ± 8.2 years) underwent a randomized double-blind crossover study involving 2-hour exposures to concentrated ambient coarse PM (164.2 ± 80.4 µg/m(3)) at an urban location (Dearborn, Michigan) versus filtered air. Cardiovascular outcomes were measured during, immediately, and 2 hours after exposures. Both systolic (1.9 mm Hg; 95% confidence interval: 0.96, 2.8; P < .001) and diastolic (1.9 mm Hg; 95% confidence interval: 1.1, 2.7; P < .001) BP levels were higher throughout coarse PM compared with filtered air exposures by mixed-model analyses. Heart rate variability, endothelial function, and arterial compliance were not significantly affected. Brief exposure to coarse PM in an urban environment raises arterial BP. These findings add mechanistic support to the contention that coarse PM may be capable of promoting cardiovascular events.

Bradykinin type 2 receptor BE1 genotype influences bradykinin-dependent vasodilation during angiotensin-converting enzyme inhibition.

To test the hypothesis that the bradykinin receptor 2 (BDKRB2) BE1+9/-9 polymorphism affects vascular responses to bradykinin, we measured the effect of intra-arterial bradykinin on forearm blood flow and tissue-type plasminogen activator (t-PA) release in 89 normotensive, nonsmoking, white American subjects in whom degradation of bradykinin was blocked by enalaprilat. BE1 genotype frequencies were +9/+9:+9/-9:-9/-9=19:42:28. BE1 genotype was associated with systolic blood pressure (121.4+/-2.8, 113.8+/-1.8, and 110.6+/-1.8 mm Hg in +9/+9, +9/-9, and -9/-9 groups, respectively; P=0.007). In the absence of enalaprilat, bradykinin-stimulated forearm blood flow, forearm vascular resistance, and net t-PA release were similar among genotype groups. Enalaprilat increased basal forearm blood flow (P=0.002) and decreased basal forearm vascular resistance (P=0.01) without affecting blood pressure. Enalaprilat enhanced the effect of bradykinin on forearm blood flow, forearm vascular resistance, and t-PA release (all P<0.001). During enalaprilat, forearm blood flow was significantly lower and forearm vascular resistance was higher in response to bradykinin in the +9/+9 compared with +9/-9 and -9/-9 genotype groups (P=0.04 for both). t-PA release tended to be decreased in response to bradykinin in the +9/+9 group (P=0.08). When analyzed separately by gender, BE1 genotype was associated with bradykinin-stimulated t-PA release in angiotensin-converting enzyme inhibitor-treated men but not women (P=0.02 and P=0.77, respectively), after controlling for body mass index. There was no effect of BE1 genotype on responses to the bradykinin type 2 receptor-independent vasodilator methacholine during enalaprilat. In conclusion, the BDKRB2 BE1 polymorphism influences bradykinin type 2 receptor-mediated vasodilation during angiotensin-converting enzyme inhibition.