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Published on: December 23, 2020
Type I Interferon Pathway-Related Hub Genes as a Potential Therapeutic Target for SARS-CoV-2 Omicron Variant-Induced
Zhiwei Lin1, Mingshan Xue1,2, Ziman Wu1
1Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
Background:
The global pandemic of COVID-19 is caused by the rapidly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical presentation of SARS-CoV-2 Omicron variant infection varies from asymptomatic to severe disease with diverse symptoms. However, the underlying mechanisms responsible for these symptoms remain incompletely understood.
Methods:
Transcriptome datasets from peripheral blood mononuclear cells (PBMCs) of COVID-19 patients infected with the Omicron variant and healthy volunteers were obtained from public databases. A comprehensive bioinformatics analysis was performed to identify hub genes associated with the Omicron variant. Hub genes were validated using quantitative RT-qPCR and clinical data. DSigDB database predicted potential therapeutic agents.
Results:
Seven hub genes (IFI44, IFI44L, MX1, OAS3, USP18, IFI27, and ISG15) were potential biomarkers for Omicron infection's symptomatic diagnosis and treatment. Type I interferon-related hub genes regulated Omicron-induced symptoms, which is supported by independent datasets and RT-qPCR validation. Immune cell analysis showed elevated monocytes and reduced lymphocytes in COVID-19 patients, which is consistent with retrospective clinical data. Additionally, ten potential therapeutic agents were screened for COVID-19 treatment, targeting the hub genes.
Conclusions:
This study provides insights into the mechanisms underlying type I interferon-related pathways in the development and recovery of COVID-19 symptoms during Omicron infection. Seven hub genes were identified as promising biological biomarkers for diagnosing and treating Omicron infection. The identified biomarkers and potential therapeutic agent offer valuable implications for Omicron's clinical manifestations and treatment strategies.
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