Gut barrier integrity biomarkers are associated with increased inflammation and predict disease status in hospitalized COVID-19 patients

The COVID-19 global pandemic persists as an endemic disease with case spikes and a significant continued burden on public health. One hallmark of severe COVID-19 is a dysregulated immune response that leads to systemic inflammation and contributes to disease severity but is not explained by viral replication alone. Severe COVID-19 has been shown to disrupt the gut microbiome and increase intestinal permeability which may contribute to immune dysregulation and systemic inflammation. Here, we investigated the differences in plasma biomarkers for intestinal permeability as well as circulating cytokines between healthy volunteers and patients hospitalized with COVID-19. Correlation analyses were used to characterize differences in biomarker relationships between groups, and a random forest model was used to assess their discriminative accuracy. Our results demonstrated that hospitalized COVID-19 patients have elevated concentrations of pro-inflammatory cytokines and microbial translocation markers, and the relationships between these biomarkers were significantly altered compared to healthy volunteers, especially those related to mucosa-associated homeostatic cytokines IL-17A and IL-23. Further, IL-6 and LBP were the top biomarkers for prediction accuracy in the random forest model. This work highlights the importance of managing microbial translocation in COVID-19 and its potential utility as a biomarker for disease severity.