About: Genetic inhibition of interleukin-6 receptor signaling and Covid-19

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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	Genetic inhibition of interleukin-6 receptor signaling and Covid-19
Creator	Affiliations, Holmes, Michael Bovijn, Jonas Lindgren, Cecilia
source	MedRxiv
abstract	There are few effective therapeutic options for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Early evidence has suggested that IL-6R blockers may confer benefit, particularly in severe coronavirus disease 2019 (Covid-19). We leveraged large-scale human genetic data to investigate whether IL6-R blockade may confer therapeutic benefit in Covid-19. A genetic instrument consisting of seven genetic variants in or close to IL6R was recently shown to be linked to altered levels of c-reactive protein (CRP), fibrinogen, circulating IL-6 and soluble IL-6R, concordant to known effects of pharmacological IL-6R blockade. We investigated the effect of these IL6R variants on risk of hospitalization for Covid-19 and other SARS-CoV-2-related outcomes using data from The Covid-19 Host Genetics Initiative. The IL6R variants were strongly associated with serum CRP levels in UK Biobank. Meta-analysis of scaled estimates revealed a lower risk of rheumatoid arthritis (OR 0.93 per 0.1 SD lower CRP, 95% CI, 0.90-0.96, P = 9.5 x 10-7), recapitulating this established indication for IL-6R blockers (e.g. tocilizumab and sarilumab). The IL-6R instrument was associated with lower risk of hospitalization for Covid-19 (OR 0.88 per 0.1 SD lower CRP, 95% CI, 0.78-0.99, P = 0.03). We found a consistent association when using a population-based control group (i.e. all non-cases; OR 0.91 per 0.1 SD lower CRP, 95% CI, 0.87-0.96, P = 4.9 x 10-4). Evaluation of further SARS-CoV-2-related outcomes suggested association with risk of SARS-CoV-2 infection, with no evidence of association with Covid-19 complicated by death or requiring respiratory support. We performed several sensitivity analyses to evaluate the robustness of our findings. Our results serve as genetic evidence for the potential efficacy of IL-6R blockade in Covid-19. Ongoing large-scale RCTs of IL-6R blockers will be instrumental in identifying the settings, including stage of disease, in which these agents may be effective.
has issue date	2020-07-19(xsd:dateTime)
bibo:doi	10.1101/2020.07.17.20155242
has license	medrxiv
sha1sum (hex)	db198b463de330ba924dc2cfb8939c55a1bccb53
schema:url	https://doi.org/10.1101/2020.07.17.20155242
resource representing a document's title	Genetic inhibition of interleukin-6 receptor signaling and Covid-19
resource representing a document's body	covid:db198b463de330ba924dc2cfb8939c55a1bccb53#body_text
is schema:about of	named entity 'Covid' named entity 'Covid-19' named entity 'RCT' named entity 'medRxiv' named entity 'IL-6R' »more»

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