About: Tissue-specific tolerance in fatal Covid-19

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Tissue-specific tolerance in fatal Covid-19
Creator	Armstrong, Stuart Hiscox, Julian Dorward, David Hartley, Catherine Penrice-Randal, Rebekah »more»
source	MedRxiv
abstract	Successful host defence against a pathogen can involve resistance or tolerance, with implications for prioritising either antimicrobial or immunomodulatory therapeutic approaches. Hyper-inflammation occurs in Covid-19 and is associated with worse outcomes. The efficacy of dexamethasone in preventing mortality in critical Covid-19 suggests that inflammation has a causal role in death. Whether this deleterious inflammation is primarily a direct response to the presence of SARS-CoV-2 requiring enhanced resistance, or an independent immunopathologic process necessitating enhanced tolerance, is unknown. Here we report an aberrant immune response in fatal Covid-19, principally involving the lung and reticuloendothelial system, that is not clearly topologically associated with the virus, indicating tissue-specific tolerance of SARS-CoV-2. We found that inflammation and organ dysfunction in fatal Covid-19 did not map to the widespread tissue and cellular distribution of SARS-CoV-2 RNA and protein, both between and within tissues. A monocyte/myeloid-rich vasculitis was identified in the lung, along with an influx of macrophages/monocytes into the parenchyma. In addition, stereotyped abnormal reticulo-endothelial responses (reactive plasmacytosis and iron-laden macrophages) were present and dissociated from the presence of virus in lymphoid tissues. Our results support virus-independent immunopathology being one of the primary mechanisms underlying fatal Covid-19. This supports prioritising pathogen tolerance as a therapeutic strategy in Covid-19, by better understanding non-injurious organ-specific viral tolerance mechanisms and targeting aberrant macrophage and plasma cell responses.
has issue date	2020-07-04(xsd:dateTime)
bibo:doi	10.1101/2020.07.02.20145003
has license	medrxiv
sha1sum (hex)	91c35e5b90d488530c9d1e3a29c235037e1fe9c0
schema:url	https://doi.org/10.1101/2020.07.02.20145003
resource representing a document's title	Tissue-specific tolerance in fatal Covid-19
resource representing a document's body	covid:91c35e5b90d488530c9d1e3a29c235037e1fe9c0#body_text
is schema:about of	named entity 'efficacy' named entity 'independent' named entity 'process' named entity 'direct' named entity 'Covid' »more»

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