Severe COVID-19 Is Fueled by Disrupted Gut Barrier Integrity

Giron, L. B.; Dweep, H.; Yin, X.; Wang, H.; Damra, M.; Goldman, A. R.; Gorman, N.; Palmer, C. S.; Tang, H.-Y.; Shaikh, M. W.; Forsyth, C. B.; Balk, R. A.; Zilberstein, N. F.; Liu, Q.; Kossenkov, A.; Keshavarzian, A.; Landay, A.; Abdel-Mohsen, M.

A disruption of the crosstalk between gut microbiota and the lung (gut-lung axis) has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. To test the possibility that a disrupted gut contributes to Coronavirus disease 2019 (COVID-19) severity, we used a systems biology approach to analyze plasma from COVID-19 patients with varying disease severity and controls. Severe COVID-19 is associated with a dramatic increase in tight junction permeability and translocation of bacterial and fungal products into blood. This intestinal disruption and microbial translocation correlate strongly with increased systemic inflammation and complement activation, lower gut metabolic function, and higher mortality. Our study highlights a previously unappreciated factor with significant clinical implications, disruption in gut barrier integrity, as a force that contributes to COVID-19 severity.