Replication of LZTFL1 gene region as a susceptibility locus for COVID-19 in Latvian population.

The severity of COVID-19 disease is partly determined by host genetic factors that have been reported by GWAS. We evaluated nine previously reported genome-wide significant associations regardless of the disease severity in a representative sample from the population of Latvia. Our cohort consisted of 475 SARS-CoV-2 positive cases, from which 146 were hospitalized individuals and 2217 controls. We found three variants from Neanderthal introgression event at the 3p21.31 region to be significantly associated with increased risk of SARS-CoV-2 infection and hospitalization status. The strongest association was displayed by rs71325088 with Bonferroni adjusted P=0.007, OR=1.46 [95% CI 1.17-1.81]. We performed fine-mapping by exploring 1 Mb region at 3p21.31 locus and identified 9 SNPs with even lower p-values with the strongest association estimated for rs2191031 P=5e-05, OR = 1.40[CI 95% 1.19-1.64] located in the LZTFL1. We show clear replication of 3p.21.31 locus in an independent cohort which favors further functional investigation of leading variants.

Tryptophan and arginine metabolism is significantly altered at the time of admission in hospital for severe COVID-19 patients: findings from longitudinal targeted metabolomics analysis

The heterogeneity in severity and outcome of COVID-19 cases points out the urgent need for early molecular characterization of patients followed by risk-stratified care. The main objective of this study was to evaluate the fluctuations of serum metabolomic profiles of COVID-19 patients with severe illness during the different disease stages in a longitudinal manner. We demonstrate a distinct metabolomic signature in serum samples of 32 hospitalized patients at the acute phase compared to the recovery period, suggesting the tryptophan (tryptophan, kynurenine, and 3-hydroxy-DL-kynurenine) and arginine (citrulline and ornithine) metabolism as contributing pathways in the immune response to SARS-CoV-2 with a potential link to the clinical severity of the disease. In addition, we provide evidence for glutamine metabolism in M2 macrophages as a complementary process and contribution of phenylalanine and tyrosine in the molecular mechanisms underlying the severe course of the infection. In conclusion, our results provide several functional metabolic markers for disease progression and severe outcome with potential clinical application. ImportanceAlthough the host defense mechanisms against SARS-CoV-2 infection are still poorly described, they are of central importance in shaping the course of the disease and the possible outcome. Metabolomic profiling may complement the lacking knowledge of the molecular mechanisms underlying clinical manifestations and pathogenesis of COVID-19. Moreover, early identification of metabolomics{square}based biomarker signatures is proved to serve as an effective approach for the prediction of disease outcome. Here we provide the list of metabolites describing the severe, acute phase of the infection and bring the evidence of crucial metabolic pathways linked to aggressive immune responses. Finally, we suggest metabolomic phenotyping as a promising method for developing personalized care strategies in COVID-19 patients.

Clinical characteristics of COVID-19 patients in Latvia under low incidence in Spring 2020

BackgroundCOVID-19 is a new infectious disease with severe disease course and high mortality in some groups. Blood tests on admission to the hospital can be useful for stratification of patients and timely correction. Our study investigated the clinical features of COVID-19 patients in Latvia and differences in blood tests in groups with different disease severity. MethodsThe retrospective study included 100 patients hospitalized in Riga East Clinical University Hospital in Spring 2020. The severity of the disease course was classified by the presence of pneumonia and its combination with respiratory failure. We have assessed blood cells count, hemoglobin, hematocrit, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), alanine aminotransferase, lactate dehydrogenase (LDH), troponin T, electrolytes, creatinine, glomerular filtration rate (GFR), D-dimer, prothrombin time, prothrombin index, oxygen saturation, and temperature on admission to the hospital. ResultsPatients were from 18 to 99 (57{+/-}18 years, 57% males). Comorbidities were found in 74% of patients. The mild, moderate, and severe groups included 35, 44, and 16 patients, respectively. In the severe group, the mortality rate was 50%. The progression to severe COVID-19 was associated positively with temperature, ESR, CRP, creatinine, LDH, and troponin T and negatively associated with oxygen saturation, eosinophils, and GFR on admission to the hospital. ConclusionsCOVID-19 severity associates with lower renal function and a higher level of inflammation and tissue damage. Eosinophils, CRP, ESR, LDH, troponin T, creatinine, and GFR are blood indicators for monitoring patients condition.

Age-related trends of lesser pelvic architecture in females and males: a computed tomography pelvimetry study / 대한해부학회지

The pelvis and the spine form a system balancing human skeleton. Within this system, the pelvis adapts to age-related changes in the spine. Previous studies were predominantly focused on changes of pelvic parameters in the sagittal plane. The aim of this study was to reveal age-related changes of lesser pelvic dimensions at different levels of the pelvic cavity in the sagittal and coronal planes and to explore sexual dimorphism in age-related tendencies. The computed tomography pelvimetry was performed on the three-dimensional workstation. The research sample included 211 females aged 18 to 84 years and 181 males aged 18 to 82 years, who underwent an examination at the Riga East University Hospital, Clinical Center “Gailezers,” Latvia. Three pelvic angles and transverse and sagittal diameters of the lesser pelvis were measured at four levels: the inlet, two axial planes in the mid-cavity, and the outlet. The results demonstrated that more pronounced age-related changes occurred in the inlet and the outlet of the lesser pelvis. The mid-cavity was less changing. The transverse diameter between acetabular centers and the sagittal diameter at the level of ischial spines were independent of age. In general, the common age-related trends were observed for pelvic parameters in females and males. A single exception was the proportion of diameters at the level of ischial spines, which decreased in males only. For parameters associated with pelvic floor diseases, age-related changes occurred in the direction of pathology.