Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients

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.

Investigating Unhealthy Alcohol Use As an Independent Risk Factor for Increased COVID-19 Disease Severity: Observational Cross-sectional Study

“…Our study further explores the effect UAU has on COVID-19 disease outcomes. Our findings are supported by prior studies that suggest that alcohol exposure may augment the activity of proinflammatory cytokines (interleukin 1β, interleukin 6, and tumor necrosis factor) in SARS-CoV-2 infection and cause pulmonary, gastrointestinal, hepatic, and neurologic organ dysfunction [15,16]. Another study demonstrated that alcohol causes severe oxidative stress due to the depletion of glutathione in the alveolar space, which leads to increased susceptibility to sepsis-mediated ARDS [17].…”

Machine learning identified distinct serum lipidomic signatures in hospitalized COVID-19-positive and COVID-19-negative patients

“…For example, Siendelar et al [36] found that a panel of 22 metabolites (including PC and LPC), predicted disease severity (as measured as need for ICU admission). Giron et al [38] reported that alterations in secondary bile acids levels, resulting from disrupted crosstalk between gut and lung, are associated with ICU admission. The reasons for these discrepancies are purely speculative.…”

Virus Infection Is an Instigator of Intestinal Dysbiosis Leading to Type 1 Diabetes

“…Respiratory infections are known to cause gastrointestinal distress, dysbiosis, and increased intestinal permeability despite an absence of virus in the GI environment (135). SARS-CoV2 patients experience noted dysbiosis and loss of intestinal integrity corresponding with more severe systemic inflammation, bacteremia, and higher mortality ratepotentially signifying a leaky gut as a contributor to worsening disease outcomes (136,137). Additionally, human immunodeficiency virus (HIV) infection has been shown to cause systemic immune activation and AIDs-related morbidity due to translocation of bacteria from the intestinal lumen (138).…”