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First Author: Livanos et al 

Journal/preprint name: medRxiv 

Tags: Immunology/Immunity, Clinical 

Summary

Livanos et al investigated the involvement of gastrointestinal (GI) in SARS-CoV-2 pathogenesis in three large cohorts from United states and Italy. GI symptoms (nausea, vomiting or diarrhea) were inversely correlated with disease severity and mortality. Patients who presented with GI symptoms had reduction of developing severe infection with an accompanying decrease in circulating inflammatory cytokines levels (IL-6, IL-8, IL-17 and CCL28). A robust expression of ACE2 receptor was observed in small intestinal enterocytes in both COVID-19 patients and controlsand SARS-CoV-2 viral particles and proteins were detected in small intestinal tissue of patients, suggesting that these cells can harbor SARS-CoV-2 antigens. However, these virions failed to cause cytopathology when co-culture with Vero E6 cells, suggesting a low number of SARS-CoV-2 present in the GI tract. Analyzing immune cell signature of intestinal tissues from COVID-19 patients showed a reduction in pro-inflammatory DCs and pDCs but increase in effector T cells, compared with controls. In addition, the RNA-Seq analysis of lamina propria (LP) and epithelial compartment (EC) showed a transcriptional remodeling of GI tissues by SARS-CoV-2 characterized by downregulation of pathways associated with inflammation and antigen presentation, yet activation of viral response signaling genes in the EC. 

Research Highlights: 

  1. COVID-19 severity was reduced in patients with GI symptoms when compared to those without GI symptoms. 

  1. Presence of GI symptoms can be used to predict reduced disease severity and mortality 225 in patients with COVID-19 

  1. COVID-19 patients with GI symptoms have reduced levels of circulating cytokines associated with inflammation and tissue damage. 

  1. The GI mucosa was endoscopically uninflamed in COVID-19 patients regardless of the severity. 

  1. Small bowel enterocytes have robust expression of Angiotensin converting enzyme-(ACE2) and harbour SARS-CoV-2 antigens 

  1. SARS-CoV-2 viral particles and protein are detectable in intestinal tissue of COVID-19 patients, but infectious virions could not be isolated from the GI tissues. 

  1. Pro-inflammatory dendritic cells are depleted, and pro-inflammatory pathway are downregulated in the GI lamina propria in COVID-19 patients 

Impact for COVID-19 research:  

  • Understand involvement and immunological landscape of GI tissues in attenuation of SARS-CoV-2 pathogenicity 

  • For clinical setting, the study suggest that GI symptoms are inversely correlated with severity of SARS-CoV-2 illness and argues in favor that GI symptoms could be used to predict disease severity. 

Methodologies: 

  • Study Typee.g. in vitro analysis   

  • Important cell lines/viral models used: PBMCs from SARS-CoV-2 patients and healthy donors. African green monkey kidney epithelial cells (Vero E6) cells. 

  • Key Techniques:  

  1. Drop ELLA Cytokine measurement. 

  1. Multiplexed proteomic assay 

  1. Mass cytometry (CyTOF) 

  1. Virus isolation and viral infection assays 

  1. RNA isolation and RT-qPCR for Viral Determination  

  1. RNA-sequencing (RNA-seq) analysis 

  1. Integrating and clustering techniques for data analysis 

 Limitations: 

  • As authors pointed, some analysis was performed in later stage of acute infection 

  • Not a limitation but interesting that the GI was not inflamed.. 

  • Large variations if the sample collection dates for the GI biopsies with some patients, samples collected during early infection and others during later time-point.  

  • COVID severity was defined based on internal scoring system of the department. (big limitation)