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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