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.

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.

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.

Aim. To evaluate the safety and efficacy of the adaptive phage therapy technique in patients with recurrent pneumonia in neurological critical care.Material and methods. The clinical study included 83 chronically critically ill patients with severe brain damage. The bacteriophage cocktail selected against specific hospital strains was administered by inhalation to 43 patients. The control group included 40 patients who received conventional antimicrobial therapy. The changes in clinical, laboratory and instrumental parameters, levels of biomarkers, microbiological and PCR tests of bronchoalveolar lavage fluid were assessed, including those in the «phage therapy with antibiotics» (n=29) and «phage therapy without antibiotics» (n=14) subgroups.Results. The groups were comparable in terms of basic parameters (age, sex, diagnosis, organ dysfunction according to APACHE II, use of vasoactive drugs) and the level of airway colonization with antibioticresistant bacterial strains. Good tolerability and absence of clinically significant side effects were observed during inhaled administration of the bacteriophage cocktail. Computed tomography on day 21 showed a significant reduction in lung damage in patients who received bacteriophages. Patients treated with bacteriophages without antibiotics had significantly lower need for mechanical ventilation. The mortality rate on day 28 did not differ significantly and was 4.7% (2/43) in the bacteriophage-treated group vs 5% (2/40) in the control group.Conclusion. The first experience of using the adaptive phage therapy technique in chronically critically ill patients in neurological intensive care demonstrated the safety of inhalational administration of the bacteriophage cocktail. The efficacy of the technique was confirmed by the treatment results obtained in the phage therapy group, which were not inferior to those in the group with conventional antibiotic therapy, while several clinical and laboratory parameters tended to improve even in patients who received bacteriophages and did not receive antibiotics.

Changes in red blood cell (RBC)-related parameters and anemia are common in both severe chronic and acute diseases. RBC-related phenotypes have a heritable component. However, it is unclear whether the contribution of genetic variability is pronounced when hematological parameters are affected by physiological stress. In this study, we analyzed RBC-related phenotypes and phenotype–genotype correlations in two exome-sequenced patient cohorts with or at a high risk for a critical illness: chronic TBI patients admitted for rehabilitation and patients with acute COVID-19. In the analysis of exome data, we focused on the cumulative effects of rare high-impact variants (qualifying variants, QVs) in specific gene sets, represented by Notch signaling pathway genes, based on the results of enrichment analysis in anemic TBI patients and three predefined gene sets for phenotypes of interest derived from GO, GWAS, and HPO resources. In both patient cohorts, anemia was associated with the cumulative effects of QVs in the GO (TBI: p = 0.0003, OR = 2.47 (1.54–4.88); COVID-19: p = 0.0004, OR = 2.12 (1.39–3.25)) and Notch pathway-derived (TBI: p = 0.0017, OR = 2.33 (1.35–4.02); COVID-19: p = 0.0012, OR =8.00 (1.79–35.74)) gene sets. In the multiple linear regression analysis, genetic variables contributed to RBC indices in patients with TBI. In COVID-19 patients, QVs in Notch pathway genes influenced RBC, HGB, and HCT levels, whereas genes from other sets influenced MCHC levels. Thus, in this exploratory study, exome data analysis yielded similar and different results in the two patient cohorts, supporting the view that genetic factors may contribute to RBC-related phenotypic performance in both severe chronic and acute health conditions.