TY - JOUR
T1 - Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients
AU - Giron, Leila B.
AU - Dweep, Harsh
AU - Yin, Xiangfan
AU - Wang, Han
AU - Damra, Mohammad
AU - Goldman, Aaron R.
AU - Gorman, Nicole
AU - Palmer, Clovis S.
AU - Tang, Hsin Yao
AU - Shaikh, Maliha W.
AU - Forsyth, Christopher B.
AU - Balk, Robert A.
AU - Zilberstein, Netanel F.
AU - Liu, Qin
AU - Kossenkov, Andrew
AU - Keshavarzian, Ali
AU - Landay, Alan
AU - Abdel-Mohsen, Mohamed
N1 - Publisher Copyright:
© Copyright © 2021 Giron, Dweep, Yin, Wang, Damra, Goldman, Gorman, Palmer, Tang, Shaikh, Forsyth, Balk, Zilberstein, Liu, Kossenkov, Keshavarzian, Landay and Abdel-Mohsen.
PY - 2021/6/9
Y1 - 2021/6/9
N2 - 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.
AB - 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.
KW - COVID-19
KW - glycomics
KW - inflammation
KW - lipidomics
KW - metabolomics
KW - microbial translocation
KW - SARS-CoV-2
KW - zonulin
UR - http://www.scopus.com/inward/record.url?scp=85108530940&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85108530940&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.686240
DO - 10.3389/fimmu.2021.686240
M3 - Article
C2 - 34177935
AN - SCOPUS:85108530940
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 686240
ER -