Plasma microbiome in COVID-19 subjects: an indicator of gut barrier defects and dysbiosis

Prasad, R.; Patton, M. J.; Floyd, J. L.; Vieira, C. P.; Fortmann, S. D.; DuPont, M.; Harbour, A.; Chen See, J. R.; Wright, J.; Lamendella, R.; Stevens, B. R.; Grant, M. B.

doi:10.1101/2021.04.06.438634

bioRxiv · 10.1101/2021.04.06.438634

Plasma microbiome in COVID-19 subjects: an indicator of gut barrier defects and dysbiosis

Prasad, R.·Patton, M. J.·Floyd, J. L.·Vieira, C. P.·Fortmann, S. D.·DuPont, M.·Harbour, A.·Chen See, J. R.·Wright, J.·Lamendella, R.·Stevens, B. R.·Grant, M. B.

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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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Prasad, R., Patton, M. J., Floyd, J. L., Vieira, C. P., Fortmann, S. D., DuPont, M., Harbour, A., Chen See, J. R., Wright, J., Lamendella, R., Stevens, B. R., Grant, M. B.. 2021-04-06. Plasma microbiome in COVID-19 subjects: an indicator of gut barrier defects and dysbiosis. https://doi.org/10.1101/2021.04.06.438634

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