Original article
Candesartan could ameliorate the COVID-19 cytokine storm

https://doi.org/10.1016/j.biopha.2020.110653Get rights and content
Under a Creative Commons license
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Highlights

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

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

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

  • 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.

Keywords

COVID-19
SARS-CoV-2
Immunity
Inflammation
NF-κB
Cytokine storm
Interferon
Angiotensin receptor blockers

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