Monday, August 24, 2020

Candesartan could ameliorate the COVID-19 cytokine storm

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Candesartan could ameliorate the COVID-19 cytokine storm


 

 

Juan M.Saavedrab
Under a Creative Commons license
open access

Highlights

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Candesartan downregulates expression of many glutamate upregulated genes in cultured neurons.

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Glutamate upregulated genes in neurons positively correlate with COVID-19 upregulated genes.

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Candesartan gene downregulation negatively correlates with COVID-19 upregulated genes.

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Candesartan downregulates genes involved in the COVID-19 cytokine storm.

Abstract

Background

Angiotensin receptor blockers (ARBs) reducing inflammation and protecting lung and brain function, could be of therapeutic efficacy in COVID-19 patients.

Methods

Using GSEA, we compared our previous transcriptome analysis of neurons injured by glutamate and treated with the ARB Candesartan (GSE67036) with transcriptional signatures from SARS-CoV-2 infected primary human bronchial epithelial cells (NHBE) and lung postmortem (GSE147507), PBMC and BALF samples (CRA002390) from COVID-19 patients.

Results

Hundreds of genes upregulated in SARS-CoV-2/COVID-19 transcriptomes were similarly upregulated by glutamate and normalized by Candesartan. Gene Ontology analysis revealed expression profiles with greatest significance and enrichment, including proinflammatory cytokine and chemokine activity, the NF-kappa B complex, alterations in innate and adaptive immunity, with many genes participating in the COVID-19 cytokine storm.

Conclusions

There are similar injury mechanisms in SARS-CoV-2 infection and neuronal injury, equally reduced by ARB treatment. This supports the hypothesis of a therapeutic role for ARBs, ameliorating the COVID-19 cytokine storm.

 
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