Association of human leukocyte antigen class II alleles with epithelial cell apoptosis and extracellular matrix production in acute COVID-19.

Introduction: Pathogenic mechanisms and long-term consequences of COVID-19 require attention in studies on SARS-CoV-2. The association of the severity of COVID-19 with genetic factors, such as human leukocyte antigen (HLA) genes, remains underexplored. Our study assessed the relationships between HLA class II alleles and COVID-19 severity and blood-based indicators of systemic inflammation and organ damage, serum markers of epithelial cell apoptosis such as caspase-cleaved CK18 fragment M30 (CK18-M30) and the extracellular matrix product hyaluronic acid (HA). Material and methods: The study included 101 hospitalized COVID-19 patients (mean age 60 ±14 years). Clinical tests were performed at admission to the hospital. The levels of CK18-M30 and HA were detected in serum by enzyme-linked immunosorbent assay (ELISA). HLA typing was performed in HLA-DRB1, -DQA1, and -DQB1 loci by the polymerase chain reaction with low-resolution sequence-specific primers. Results: Sixty-one patients had a non-severe and 40 had a severe or critical disease course (following the WHO definition). The severity was associated with older age, male gender, higher HA, CK18-M30, and some indicators of inflammation. Despite the lack of direct association between HLA alleles and the severity of COVID-19, the presence of HLA-DRB1*04 and 12 alleles in the genotype was associated with lowered or elevated HA, respectively. The HLA-DQB1*03:01 allele was associated with lowered CK18-M30, aspartate aminotransferase, and ferritin. In addition, HLA-DQB1*06:01 was associated with elevated alanine aminotransferase. Conclusions: Associations of HLA class II alleles with markers of epithelial cell apoptosis and extracellular matrix production indirectly support the influence of HLA genes on acute COVID-19 severity.

Seroprevalence of diphtheria and measles antibodies and their association with demographics, self-reported immunity, and immunogenetic factors in healthcare workers in Latvia.

Latvia is among European countries with outbreaks of diphtheria and measles. Healthcare workers (HCW) are exposed to infections and can transmit them to unvaccinated patients. We assessed the seroprevalence of antibodies against diphtheria and measles and their association with demographics, self-reported immunity, the presence of the HLA-B27 allele, and level of interferon regulatory factor 5 (IRF5) in Latvian HCW. Anti-diphtheria and anti-measles IgG antibodies and the level of IRF5 in serum were tested by enzyme immunoassay. The presence of the HLA-B27 allele was detected by a real-time polymerase chain reaction. The study involved 176 HCW, including 29% doctors and 44% nurses. Among HCW, 95.5% were seropositive for diphtheria. However, only 65.9% had full seroprotection against it. The seronegativity for measles (21.6%) was higher than for diphtheria (4.5%) without differences in gender and medical staff groups. Older age was associated with waning immunity against diphtheria and a higher rate of seropositivity for measles. Considered immunogenetic factors did not affect the level of antibodies, and variability of the level of IRF5 in serum can reflect ageing processes. Self-reported vaccination status had a low informative value regarding full seroprotection against diphtheria and seropositivity for measles indicating the need for pre-vaccination IgG screening in planning the booster vaccination.

Post-COVID-19 Liver Injury: Comprehensive Imaging With Multiparametric Ultrasound.

OBJECTIVES: This study aimed to define patterns of liver injury after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using multiparametric ultrasound (mpUS) in a variable patient population with differing severities of COVID-19. METHODS: Ninety patients were enrolled into the study: 56 had SARS-CoV-2 3-9 months prior to enrolment; 34 served as a clinically healthy control group. All patients underwent an mpUS evaluation of the liver (elastography, dispersion and attenuation imaging). Seventy-six patients had abdominal magnetic resonance (MR) and noncontrast enhanced thoracic computed tomography (CT) scans performed at the same day. All patients were screened for biochemical markers of liver injury. RESULTS: Liver elasticity, viscosity, and steatosis values were significantly altered in patients after COVID-19, with particularly higher fibrosis scores compared to the control group (P < .001). Increased biochemical markers of liver injury correlated with changes in mpUS (P < .05), but not with findings on CT or MR findings. Seventeen of 34 hospitalized patients had a moderate or severe course of the disease course with more pronounced changes in mpUS. Increased body mass index was found to influence liver injury and correlated with more severe forms of COVID-19 (P < .001). CONCLUSIONS: COVID-19 can cause liver injury observable using mpUS. More severe forms of COVID-19 and patient obesity are related to increased values of liver damage observed. In comparison to MRI and CT, mpUS appears to be more sensitive to involvement of liver parenchyma. Further research is warranted to establish this promising method for evaluating post-COVID-19 liver involvement in the aftermath of the pandemic.

Amino Acid 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 suggest that glutamine deprivation may further result in inhibited M2 macrophage polarization as a complementary process, and highlight the 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. IMPORTANCE Although 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-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.

Expression of ORAI1 and STIM1 genes in blood of patients with pulmonary tuberculosis.

This study aimed to detect the expression level of ORAI1 and STIM1 genes in blood of patients with bilateral pulmonary tuberculosis (TB) in comparison with the control group. Both genes encode proteins providing store-operated Ca2+ entry (SOCE) into the cells, including immune cells, to activate transcriptional factors for producing cytokines and inflammation-restricting proteins. The study included 45 patients with confirmed TB, aged 20 to 86, and 35 volunteers, aged from 21 to 73, without active TB infection. The expression of ORAI1 and STIM1 genes in blood was performed by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as the referent gene. Inflammation was assessed by levels of interferon γ (IFN-γ) and interleukin 18 (IL-18) in serum (ELISA method). The results showed lower expression of ORAI1 in blood and higher levels of IFN-γ and IL-18 in serum of TB patients than that of the control group and no differences in expression of the STIM1 gene. It indicates some impairment in the SOCE mechanism of immune cells, which is associated with TB.

Intriguing findings of liver fibrosis following COVID-19.

BACKGROUND: Studies on a new coronavirus disease (COVID-19) show the elevation of liver enzymes and liver fibrosis index (FIB-4) independently on pre-existing liver diseases. It points to increased liver fibrogenesis during acute COVID-19 with possible long-term consequences. This study aimed to assess liver fibrosis in COVID-19 patients by serum hyaluronic acid (HA) and FIB-4. METHODS: The study included the acute COVID-19 group (66 patients, 50% females, mean age 58.3 ± 14.6), the post-COVID group (58 patients in 3-6 months after the recovery, 47% females, mean age 41.2 ± 13.4), and a control group (17 people, 47% females, mean age 42.8 ± 11.0). Ultrasound elastography was performed in the post-COVID and control groups. RESULTS: Sixty-five percent of the acute COVID-19 group had increased FIB-4 (> 1.45), and 38% of patients had FIB-4 ≥ 3.25. After matching by demographics, 52% of acute COVID-19 and 5% of the post-COVID group had FIB-4 > 1.45, and 29% and 2% of patients had FIB-4 ≥ 3.25, respectively. Increased serum HA (≥ 75 ng/ml) was observed in 54% of the acute COVID-19 and 15% of the post-COVID group. In the acute COVID-19 group, HA positively correlated with FIB-4, AST, ALT, LDH, IL-6, and ferritin and negatively with blood oxygen saturation. In the post-COVID group, HA did not correlate with FIB-4, but it was positively associated with higher liver stiffness and ALT. CONCLUSION: More than half of acute COVID-19 patients had increased serum HA and FIB-4 related to liver function tests, inflammatory markers, and blood oxygen saturation. It provides evidence for the induction of liver fibrosis by multiple factors during acute COVID-19. Findings also indicate possible liver fibrosis in about 5% of the post-COVID group.

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

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.