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Biomed Pharmacother ; 131: 110653, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-722385

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.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/pharmacology , Benzimidazoles/pharmacology , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/drug therapy , Pneumonia, Viral/drug therapy , Tetrazoles/pharmacology , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Biphenyl Compounds , Bronchi/cytology , Bronchoalveolar Lavage Fluid/virology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/virology , Cytokine Release Syndrome/virology , Epithelial Cells/drug effects , Epithelial Cells/virology , Gene Expression Profiling , Humans , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/virology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , SARS-CoV-2 , Transcriptome , COVID-19 Drug Treatment
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