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Authors: He et al.

Link to paper: https://www.biorxiv.org/content/10.1101/2020.05.11.088500v1

Journal/ Pre-Print: bioRxiv

Tags: Bioinformatics, Cell Biology

Research Highlights 

1. A meta-analysis of scRNAseq datasets shows that in brain and heart tissue of mice and humans, ACE2 mRNA is mostly found in microvascular mural cells (pericytes, vascular smooth muscle cells) but not on endothelial cells. In the lung, ACE2 mRNA is mostly found in alveolar type-2 (AT-2) cells and multiciliated airway epithelial cells.

2. Immunofluorescence microscopy of brain and heart tissue of mice shows that Ace2 protein expression is mostly found in microvascular mural cells (pericytes, vascular smooth muscle cells) but not on endothelial cells.

3. Pericyte-deficient mice have increased Von Willebrand Factor production and release by endothelial cells, platelet aggregation, and fibrin deposition in brain microvasculature.

Summary

The authors describe a high incidence of coagulopathies in a small cohort of 20 ICU patients; no SARS-CoV2 infection models or Covid-19 patient samples are used. Based on meta-analysis of existing datasets, showing that pericytes have high ACE2 expression, they postulate that infection of pericytes causes SARS-CoV2-induced coagulopathies. Known risk factors for severe Covid-19, e.g. hypertension, diabetes, and obesity, increase endothelial permeability. Hence, pericytes would be more exposed to viral particles in the blood. Infection and immune attack of pericytes might further exacerbate vascular inflammation and permeability, and SARS-CoV2-infected pericytes would induce thrombogenicity and hypercoagulation by stimulating endothelial VWF production.

Impact for SARS-CoV2/COVID19 research efforts

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19: The authors provide a hypothesis as to why Covid-19 patients have an increased risk of hypercoagulopathy, thrombogenesis and thromboembolism.

Study Type

· In silico study / bioinformatics study

· In vivo study (mouse)

Strengths and limitations of the paper

Novelty: No novel data, just novel analysis of existing data from published/submitted papers that brings new insight on ACE2 expression, validated with imaging. The pericyte hypothesis is also novel.

Standing in the field: The high incidence of coagulopathies in severe Covid-19 patients has been confirmed in other studies.

Appropriate statistics: No, no statistical testing performed at all.

Viral model used: none

Translatability: Not yet, hypothesis needs to be tested first.

Main limitations: > The authors postulate an attractive hypothesis but have not tested it experimentally.

> Only data from brain, heart, and lung tissue were used. There is a brief mention of hepatic and kidney pericytes in the discussion section, but no data are shown.

> The authors do not discuss that there is limited evidence for infectious viral particles being present in blood, which is central to their hypothesis.