Plasma microbiome in COVID-19 subjects: an indicator of gut barrier defects and dysbiosis
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Abstract
The gut is a well-established route of infection and target for viral damage by SARS-CoV-2. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal ( GI ) symptoms. We asked whether the analysis of plasma could provide insight into gut barrier dysfunction in patients with COVID-19 infection. Plasma samples of COVID-19 patients (n=30) and healthy control (n=16) were collected during hospitalization. Plasma microbiome was analyzed using 16S rRNA sequencing, metatranscriptomic analysis, and gut permeability markers including FABP-2, PGN and LPS in both patient cohorts. Almost 65% (9 out 14) COVID-19 patients showed abnormal presence of gut microbes in their bloodstream. Plasma samples contained predominately Proteobacteria, Firmicutes, and Actinobacteria . The abundance of gram-negative bacteria ( Acinetobacter, Nitrospirillum, Cupriavidus, Pseudomonas, Aquabacterium, Burkholderia, Caballeronia, Parabhurkholderia, Bravibacterium, and Sphingomonas ) was higher than the gram-positive bacteria ( Staphylococcus and Lactobacillus ) in COVID-19 subjects. The levels of plasma gut permeability markers FABP2 (1282±199.6 vs 838.1±91.33; p=0.0757), PGN (34.64±3.178 vs 17.53±2.12; p<0.0001), and LPS (405.5±48.37 vs 249.6±17.06; p=0.0049) were higher in COVID-19 patients compared to healthy subjects. These findings support that the intestine may represent a source for bacteremia and may contribute to worsening COVID-19 outcomes. Therapies targeting the gut and prevention of gut barrier defects may represent a strategy to improve outcomes in COVID-19 patients.
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SciScore for 10.1101/2021.04.06.438634: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: During hospitalization of the COVID-19 patients at UAB hospital, blood samples were collected under sterile conditions following Institutional Review Board guidelines. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources 16S rRNA sequencing was performed using an Illumina MiSeq v2 chemistry with paired-end 250 base pair reads as per the Earth Microbiome Project’s protocol20. Earth Microbiome Project’ssuggested: NoneInitial quality in the form of Phred q scores was determined using Qiime2, while cumulative expected error for each position … SciScore for 10.1101/2021.04.06.438634: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: During hospitalization of the COVID-19 patients at UAB hospital, blood samples were collected under sterile conditions following Institutional Review Board guidelines. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources 16S rRNA sequencing was performed using an Illumina MiSeq v2 chemistry with paired-end 250 base pair reads as per the Earth Microbiome Project’s protocol20. Earth Microbiome Project’ssuggested: NoneInitial quality in the form of Phred q scores was determined using Qiime2, while cumulative expected error for each position was determined with VSEARCH22. Phredsuggested: (Phred, RRID:SCR_001017)Statistical analysis: Data were evaluated for presence of outliers and adherence to a normal distribution using GraphPad Prism, version 8.1 software. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This study has limitations including the absence of plasma microbiome samples in control subjects and the rather small size for COVID-19 subjects. Despite the limitations, we show conclusively that gut barrier leakage occurs in COVID-19 subjects. Taken together, we summarized our observations and show the presence of pathogenic bacteria in the plasma of COVID-19 subjects (Fig. 5). SARS-CoV-2 infection disrupts the gut barrier and leads to elevation of systemic bacterial lipopolysaccharide and peptidoglycan and serves to enhance systemic inflammation. Therefore, leaky gut and microbial dysbiosis could contribute to cytokine storm in patients severely ill with COVID-19.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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