COVID-19 patients with acute respiratory distress syndrome (ARDS) have an immune imbalance when systemic inflammation and dysfunction of circulating T and B cells lead to a more severe disease. Using TREC/KREC analysis, we studied the level of mature naive T and B cells in peripheral blood of COVID-19 patients and its relationship with clinical and laboratory data. TREC/KREC analysis was performed by multiplex real-time quantitative PCR on a sample of 36 patients aged 45 years or younger. The reduced TREC/KREC level was observed in ARDS patients compared with non-ARDS patients, and similar results were found for the deceased patients. During days 6 to 20 of hospitalization, a higher neutrophil-to-lymphocyte ratio (NLR) was detected in ARDS patients compared with non-ARDS patients. TREC/KREC negatively correlated with NLR; the highest correlation was recorded for TREC per 100,000 cells with the coefficient of determination R² = 0.527. Thus, TREC/KREC analysis is a potential prognostic marker for assessing the severity and outcome in COVID-19.

Pneumonia is an acute infectious disease with high morbidity and mortality rates. Pneumonia’s development, severity and outcome depend on age, comorbidities and the host immune response. In this study, we combined theoretical and experimental investigations to characterize pneumonia and its comorbidities as well as to assess the host immune response measured by TREC/KREC levels in patients with pneumonia. The theoretical study was carried out using the Columbia Open Health Data (COHD) resource, which provides access to clinical concept prevalence and co-occurrence from electronic health records. The experimental study included TREC/KREC assays in young adults (18–40 years) with community-acquired (CAP) (n = 164) or nosocomial (NP) (n = 99) pneumonia and healthy controls (n = 170). Co-occurring rates between pneumonia, sepsis, acute respiratory distress syndrome (ARDS) and some other related conditions common in intensive care units were the top among 4170, 3382 and 963 comorbidities in pneumonia, sepsis and ARDS, respectively. CAP patients had higher TREC levels, while NP patients had lower TREC/KREC levels compared to controls. Low TREC and KREC levels were predictive for the development of NP, ARDS, sepsis and lethal outcome (AUC_TREC in the range 0.71–0.82, AUC_KREC in the range 0.67–0.74). TREC/KREC analysis can be considered as a potential prognostic test in patients with pneumonia.

The aim of the study was to investigate the serial changes in inflammatory indices derived from blood cell counts and C-reactive protein (CRP) levels in COVID-19 patients with good and poor outcomes. We retrospectively analyzed the serial changes in the inflammatory indices in 169 COVID-19 patients. Comparative analyses were performed on the first and last days of a hospital stay or death and serially from day 1 to day 30 from the symptom onset. On admission, non-survivors had higher CRP to lymphocytes ratio (CLR) and multi-inflammatory index (MII) values than survivors, while at the time of discharge/death, the largest differences were found for the neutrophil to lymphocyte ratio (NLR), systemic inflammation response index (SIRI), and MII. A significant decrease in NLR, CLR, and MII by the time of discharge was documented in the survivors, and a significant increase in NLR was documented in the non-survivors. The NLR was the only one that remained significant from days 7–30 of disease in intergroup comparisons. The correlation between the indices and the outcome was observed starting from days 13–15. The changes in the index values over time proved to be more helpful in predicting COVID-19 outcomes than those measured on admission. The values of the inflammatory indices could reliably predict the outcome no earlier than days 13–15 of the disease.

Dysregulation in cytokine production has been linked to the pathogenesis of various immune-mediated traits, in which genetic variability contributes to the etiopathogenesis. GWA studies have identified many genetic variants in or near cytokine genes, nonetheless, the translation of these findings into knowledge of functional determinants of complex traits remains a fundamental challenge. In this study we aimed at collection, analysis and interpretation of data on cytokines focused on their tissue-specific expression, eQTLs and GWAS traits. Using GO annotations, we generated a list of 314 cytokines and analyzed them with the GTEx resource. Cytokines were highly tissue-specific, 82.3% of cytokines had Tau expression metrics ≥ 0.8. In total, 3077 associations for 1760 unique SNPs in or near 244 cytokines were mapped in the NHGRI-EBI GWAS Catalog. According to the Experimental Factor Ontology resource, the largest numbers of disease associations were related to ‘Inflammatory disease’, ‘Immune system disease’ and ‘Asthma’. The GTEx-based analysis revealed that among GWAS SNPs, 1142 SNPs had eQTL effects and influenced expression levels of 999 eGenes, among them 178 cytokines. Several types of enrichment analysis showed that it was cytokines expression variability that fundamentally contributed to the molecular origins of considered immune-mediated conditions.

Traumatic brain injury (TBI) is the leading cause of global mortality and morbidity. Because TBI is accident-related, the role of genetics in predisposing to TBI has been largely unexplored. However, the likelihood of injury may not be entirely random and may be associated with certain physical and mental characteristics. In this study, we analyzed the exomes of 50 patients undergoing rehabilitation after TBI. Patients were divided into three groups according to rehabilitation outcome: improvement, no change, and deterioration/death. We focused on rare, potentially functional missense and high-impact variants in genes intolerant to these variants. The concordant results from the three independent groups of patients allowed for the suggestion of the existence of a genetic predisposition to TBI, associated with rare functional variations in intolerant genes, with a prevalent dominant mode of inheritance and neurological manifestations in the genetic phenotypes according to the OMIM database. Forty-four of the 50 patients had one or more rare, potentially deleterious variants in one or more neurological genes. Comparison of these results with those of a 50-sampled matched non-TBI cohort revealed significant differences: P = 2.6 × 10⁻³, OR = 4.89 (1.77–13.47). There were no differences in the distribution of the genes of interest between the TBI patient groups. Our exploratory study provides new insights into the impact of genetics on TBI risk and is the first to address potential genetic susceptibility to TBI.

The principal genetic demographic parameters that describe migration processes affecting the structure of the St. Petersburg population gene pool were determined on the basis of the...