Gut Barrier Integrity and COVID-19 Severity

Gut microbiome is known to release enzymes that degrade plasma glycans which regulate inflammation.

The overactive immune response to an infection with COVID-19 is known to lead to significant lung inflammation. This inflammation can lead to a disruption in gut barrier integrity and can increase the permeability to gut microbes and their products. This in turn can exacerbate the inflammation further, and can result in a positive feedback loop.

It is believed that this crosstalk between the gut and the lungs can be a driver in the severity of a COVID-19 infection. Recently, investigators attempted to study this potential link between the loss of gut barrier integrity and COVID-19 severity. The data was presented during the Conference on Retroviruses and Opportunistic Infections (CROI) 2021 virtual sessions.

Investigators employed a multi-omic systems biology approach to analyze plasma samples from 60 age and gender-matched COVID-19 patients with varying levels of disease severity. Using the diagnostic enzyme-linked immunosorbent assay (ELISA), they measured their markers and drivers of tight junction permeability and microbial translocation against 20 SARS-CoV-2 negative controls.

Inflammation and immune activation markers were also measured with ELISA, as well as a multiplex cytokine array. Additionally, they measured untargeted metabolomic and lipidomic analyses using mass spectrometry and plasma glycomes using capillary electrophoresis and lectin microarrays. Multiple comparisons were accounted for using a false discovery rate (FDR).

Findings from the study showed that severe COVID-19 is associated with a dramatic increase in the level of the only known physiological driver of intestinal tight junction permeability called zonulin. This increased permeability was associated with translocation of bacterial and fungal products into the blood. The level of intestinal permeability and microbial translocation was correlated with increased systemic inflammation.

Other findings demonstrated that a severe COVID-19 infection disrupted the levels of metabolomic and lipidomic markers of gut and gut microbiota, and led to a loss of the anti-complement activation galactosylated glycans from plasma and IgG glycoproteins.

“Our data provide multiple layers of evidence that a previously unappreciated factor with significant clinical implications, disruption in gut barrier integrity, is a potential force that contributes to COVID-19 severity,” the authors wrote.