About: Rapid endothelialitis and vascular inflammation characterise SARS-CoV-2 infection in a human lung-on-chip model

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About: Rapid endothelialitis and vascular inflammation characterise SARS-CoV-2 infection in a human lung-on-chip model Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Rapid endothelialitis and vascular inflammation characterise SARS-CoV-2 infection in a human lung-on-chip model
Creator	Dhar ^1, Neeraj Mancini, Gian-Filippo Mckinney, John Sharma ^1, Kunal Sordet-Dessimoz, Jessica »more»
source	BioRxiv
abstract	Background Severe manifestations of COVID-19 include hypercoagulopathies and systemic endothelialitis. The underlying dynamics of damage to the vasculature, and whether it is a direct consequence of endothelial infection or an indirect consequence of immune cell mediated cytokine storms is unknown. This is in part because in vitro infection models are typically monocultures of epithelial cells or fail to recapitulate vascular physiology. Methods We establish a vascularised lung-on-chip infection model consisting of a co-culture of primary human alveolar epithelial cells (‘epithelial’) and human lung microvascular endothelial cells (‘endothelial’), with the optional addition of CD14+ macrophages to the epithelial side. A combination of qRT-PCR, RNAscope, immunofluorescence, and ELISA measurements are used to study the dynamics of viral replication and host responses to a low dose infection of SARS-CoV-2 delivered to the apical surface of the epithelial face maintained at an air-liquid interface. Findings SARS-CoV-2 inoculation does not lead to a productive amplification of infectious virions. However, both genomic and antisense viral RNA can be found in endothelial cells within 1-day post infection (dpi) and persist upto 3 dpi. This generates an NF-KB inflammatory response typified by IL-6 secretion and a weak antiviral interferon response even in the absence of immune cells. Endothelial inflammation leads to a progressive loss of barrier integrity, a subset of cells also shows a transient hyperplasic phenotype. Administration of Tocilizumab slows the loss of barrier integrity but does not reduce the occurrence of the latter. Interpretation Endothelial infection can occur through basolateral transmission from infected epithelial cells at the air-liquid interface. SARS-CoV-2 mediated inflammation occurs despite the lack of rapid viral replication and the consequences are cell-type dependent. Infected endothelial cells might be a key source of circulating IL-6 in COVID-19 patients. Vascular damage occurs independently of immune-cell mediated cytokine storms, whose effect would only exacerbate the damage. Finding Core support from EPEL.
has issue date	2020-08-10(xsd:dateTime)
bibo:doi	10.1101/2020.08.10.243220
has license	biorxiv
sha1sum (hex)	43424528252ae927415662de056ed7aa70793835
schema:url	https://doi.org/10.1101/2020.08.10.243220
resource representing a document's title	Rapid endothelialitis and vascular inflammation characterise SARS-CoV-2 infection in a human lung-on-chip model
schema:publication	bioRxiv
resource representing a document's body	covid:43424528252ae927415662de056ed7aa70793835#body_text
is schema:about of	named entity 'leads' named entity 'day' named entity 'Tocilizumab' named entity 'human lung' named entity 'CD14' »more»

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