Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.
The microbial populations in the gut microbiome have recently been associated with COVID-19 disease severity. However, a causal impact of the gut microbiome on COVID-19 patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. Antibiotics and other treatments during COVID-19 can potentially confound microbiome associations. We therefore first demonstrate that the gut microbiome is directly affected by SARS-CoV-2 infection in a dose-dependent manner in a mouse model, causally linking viral infection and gut microbiome dysbiosis. Comparison with stool samples collected from 97 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, paralleling our observations in the animal model. Specifically, we observed blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species in hospitalized COVID-19 patients. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data obtained from these patients suggest that bacteria translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID 19.
The microbial populations in the gut microbiome have recently been associated with COVID-19 disease severity. However, a causal impact of the gut microbiome on COVID-19 patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. Antibiotics and other treatments during COVID-19 can potentially confound microbiome associations. We therefore first demonstrate that the gut microbiome is directly affected by SARS-CoV-2 infection in a dose-dependent manner in a mouse model, causally linking viral infection and gut microbiome dysbiosis. Comparison with stool samples collected from 101 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, paralleling our observations in the animal model. Specifically, we observed blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species in hospitalized COVID-19 patients. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data obtained from these patients suggest that bacteria translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.
DETERMINATION OF TOTAL ADRENAL CHOLESTEROLshortening in the prothrombin time, equivalent to a 50% increase in prothrombin, is accomplished by an eluate without prothrombin and containing an infinitesimal amount of thrombin, suggests that the substances responsible are accessory to the main reaction and not direct contributors to the thrombin One might speculate endlessly over the synergism of SA and AHF shown in Fig. 2.We were surprised to find that supernormal prothrombic activity could not be obtained without -4HF, despite the use of a potent brain thromboplastin. Possibly the simplest and least controversial inference which might be drawn from the experiments of Fig. 2 is that AHF, under certain conditions, is merely another of the numerous variables in the prothrombin time test.1. An eluate from BaS04-adsorption of normal serum is shown to have a marked effect on the clotting time in hemophilia without altering the defect in prothrombin utilization. 2. The eluate is shown to operate chiefly by reducing the latent period of prothrombin utilization. 3. The effect of this eluate on AHF assays is discussed. 4. The necessity of platelets for prothrombin conver-pool. Summary.sion is demonstrated again under different experimental conditions. 5. AHF is shown to be required for the demonstration of maximal prothrombic activity in the prothrombin time test.
molecules to circulation in order to maintain the high-viscosity needed for efficient lubrication by synovial fluid. One example of this challenge is that most contrast-enhanced clinical imaging protocols define cartilage defects by exclusion of systemically delivered small molecule contrast agents. This architecture presents a challenge to effective drug delivery for treating OA. We hypothesized that cationic TAT-PTDs (Peptide Transduction Domains) would enable in vivo drug delivery into synovial joints because of electrostatic attraction between the cationic TAT PTD and anionic cartilage glycosaminoglycans. Methods: To address our hypothesis, we utilized a non-invasive in vivo model of post-traumatic OA. In this model, joints are subjected to a single mechanical overload which results in upregulation of IL-6 mRNA. 24 hours prior to injury, we treated the animals with siRNA complexed to a TAT-PTD fusion protein for delivery of siRNA. The fusion protein, TAT PTD-DRBD (Protein Transduction Domain coupled to a Double-stranded RNA Binding Domain), was complexed to siRNA at a 1:8 molar ratio of siRNA to protein. Controls included both untreated and off-target-treated joints. Therapeutic compounds and controls were delivered via 12 mL injection to the selected knee joint using a medial approach. Joints were injured by a single mechanical overload applied at 500 mm/s which results in a mid-substance tear of the ACL. Joints were harvested for qPCR 1 week after injury.
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