Increasing evidence suggests that gut dysbiosis is associated with coronavirus disease 2019 (COVID-19) infection and may persist long after disease resolution. The excessive use of antimicrobials in patients with COVID-19 can lead to additional destruction of the microbiota, as well as to the growth and spread of antimicrobial resistance. The problem of bacterial resistance to antibiotics encourages the search for alternative methods of limiting bacterial growth and restoring the normal balance of the microbiota in the human body. Bacteriophages are promising candidates as potential regulators of the microbiota. In the present study, two complex phage cocktails targeting multiple bacterial species were used in the rehabilitation of thirty patients after COVID-19, and the effectiveness of the bacteriophages against the clinical strain of Klebsiella pneumoniae was evaluated for the first time using real-time visualization on a 3D Cell Explorer microscope. Application of phage cocktails for two weeks showed safety and the absence of adverse effects. An almost threefold statistically significant decrease in the anaerobic imbalance ratio, together with an erythrocyte sedimentation rate (ESR), was detected. This work will serve as a starting point for a broader and more detailed study of the use of phages and their effects on the microbiome.

Objective(s) : Since there is increasing evidence of serious deterioration in long-term Quality of Life (QoL) in COVID-19 intensive care unit (ICU) survivors, we identified predictors of poor quality of life in these patients. Design : Prospective cohort study. Setting : Research hospital repurposed in to a COVID-19 center. Participants : Consecutive patients admitted in COVID-19 ICU between March and June 2020. Interventions : A SF-36 questionnaire, which includes physical and mental items, was used 6 months after patients discharge. Measurements and Main Results : 403 patients were managed in the ICU with a hospital mortality of 181/403 (44.9%) while 16 (4.0%) further patients died within 6 months. Among the 125 questionnaire responders, only 32.0% and 52% had a normal quality of life in terms of the physical and mental component of health. Multivariable analysis identified low-molecular-weight heparin treatment in ICU as the only modifiable factor associated with an increase in physical component of QoL OR: 3.341 (95%CI 1.298-8.599), p=0.012, while age ≥52 years OR 0.223 and female sex OR 0.321 were significantly associated with a decrease in the physical component. Medical history of cerebrovascular insufficiency was significantly associated with a decrease in mental component of QoL OR: 0.125, while the only factor associated with an increase in the mental health component was BMI ≥ 27.6 kg / m2 OR 7.466. Conclusions : In COVID-19 intensive care unit survivors we identified treatment with low molecular weight heparin as a predictor of improved physical component of QoL at 6-months.

The increased plasma levels of von Willebrand factor (VWF) in patients with COVID-19 was reported in many studies, and its correlation with disease severity and mortality suggest its important role in the pathogenesis of thrombosis in COVID-19. We performed histological and immunohistochemical studies of the lungs of 29 patients who died from COVID-19. We found a significant increase in the intensity of immunohistochemical reaction for VWF in the pulmonary vascular endothelium when the disease duration was more than 10 days. In the patients who had thrombotic complications, the VWF immunostaining in the pulmonary vascular endothelium was significantly more intense than in nonsurvivors without thrombotic complications. Duration of disease and thrombotic complications were found to be independent predictors of increased VWF immunostaining in the endothelium of pulmonary vessels. We also revealed that bacterial pneumonia was associated with increased VWF staining intensity in pulmonary arterial, arteriolar, and venular endothelium, while lung ventilation was an independent predictor of increased VWF immunostaining in arterial endothelium. The results of the study demonstrated an important role of endothelial VWF in the pathogenesis of thrombus formation in COVID-19.

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COVID-19-related thrombosis affects the venous and arterial systems. Data from 156 autopsies of COVID-19 patients were retrospectively analyzed to investigate the pattern of thrombotic complications and factors associated with pulmonary artery thrombosis and thromboembolism. Thrombotic complications were observed in a significant proportion (n = 68, 44%), with pulmonary artery thrombosis the most frequently identified thrombotic event (42, 27%). Multivariate analysis revealed that the length of hospital stay (OR 1.1, p = 0.004), neutrophil infiltration in the alveolar spaces (OR 3.6, p = 0.002), and the absence of hyaline membranes (OR 0.1, p = 0.01) were associated with thrombotic complications. Neutrophil infiltration in the alveolar spaces (OR 8, p < 0.001) and the absence of hyaline membranes (OR 0.1, p = 0.003) were also independent predictors of pulmonary artery thrombosis. The association of pulmonary artery thrombosis with an absence of hyaline membranes suggests it occurs later in the course of COVID-19 infection. As neutrophil infiltration in the alveolar spaces may indicate bacterial infection, our studies suggest the consideration of bacterial infections in these critically ill patients.

Postoperative complications in cardiovascular surgery remain an important unresolved problem, in particular in patients with aortic aneurysm. The role of the altered microbiota in such patients is of great interest. The aim of this pilot study was to determine whether the development of postoperative complications in patients with aortic aneurysm is related with initial or acquired disorders of microbiota metabolism by monitoring the level of some aromatic microbial metabolites (AMMs) circulating in the blood before the surgery and in the early postoperative period. The study comprised patients with aortic aneurysm (n = 79), including patients without complications (n = 36) and patients with all types of complications (n = 43). The serum samples from the patients were collected before and 6 h after the end of the surgery. The most significant results were obtained for the sum of three sepsis-associated AMMs. This level was higher before the surgery in comparison with that of healthy volunteers (n = 48), p < 0.001, and it was also higher in the early postoperative period in patients with all types of complications compared to those without complications, p = 0.001; the area under the ROC curve, the cut-off value, and the odds ratio were 0.7; 2.9 µmol/L, and 5.5, respectively. Impaired microbiota metabolism is important in the development of complications after complex reconstructive aortic surgery, which is the basis for the search for a new prevention strategy.

Despite the enormous interest in COVID-19, there is no clear understanding of the mechanisms underlying the neurological symptoms in COVID-19. Microglia have been hypothesized to be a potential mediator of the neurological manifestations associated with COVID-19. In most existing studies to date, morphological changes in internal organs, including the brain, are considered in isolation from clinical data and defined as a consequence of COVID-19. We performed histological immunohistochemical (IHC) studies of brain autopsy materials of 18 patients who had died from COVID-19. We evaluated the relationship of microglial changes with the clinical and demographic characteristics of the patients. The results revealed neuronal alterations and circulatory disturbances. We found an inverse correlation between the integral density Iba-1 (microglia/macrophage-specific marker) IHC staining and the duration of the disease (R = −0.81, p = 0.001), which may indicate a reduced activity of microglia and do not exclude their damage in the long-term course of COVID-19. The integral density of Iba-1 IHC staining was not associated with other clinical and demographic factors. We observed a significantly higher number of microglial cells in close contact with neurons in female patients, which confirms gender differences in the course of the disease, indicating the need to study the disease from the standpoint of personalized medicine.