AUTHOR=Giron Leila B. , Dweep Harsh , Yin Xiangfan , Wang Han , Damra Mohammad , Goldman Aaron R. , Gorman Nicole , Palmer Clovis S. , Tang Hsin-Yao , Shaikh Maliha W. , Forsyth Christopher B. , Balk Robert A. , Zilberstein Netanel F. , Liu Qin , Kossenkov Andrew , Keshavarzian Ali , Landay Alan , Abdel-Mohsen Mohamed TITLE=Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.686240 DOI=10.3389/fimmu.2021.686240 ISSN=1664-3224 ABSTRACT=

A disruption of the crosstalk between the gut and the lung 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. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.