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.

Chronic obstructive pulmonary disease (COPD) is a prevalent chronic airway disease globally, with ferroptosis playing a role in its occurrence and progression. Isorhamnetin (ISO) has been shown to have anti-inflammatory and antioxidant properties, but its therapeutic effect on COPD and underlying mechanism are not well understood. This study aimed to investigate the therapeutic potential of ISO in COPD using network pharmacology and experimental validation. Through analysis, 11 potential targets for ISO treatment in COPD were identified, with the NRF2/SLC7A11/GPX4pathway playing a key role. Molecular docking studies suggested that ISO may bind to NRF2, SLC7A11, NQO1, AKR1C3, and AKR1C1. Experimental results demonstrated that ISO reduced ferroptosis induced by cigarette smoke extract in BEAS-2B cells and decreased airway inflammation in a mouse COPD model, while upregulating the expression of NRF2, SLC7A11, and GPX4. Overall, these findings provide insights into the potential therapeutic effects of ISO on COPD by targeting ferroptosis in the airway epithelium, with the NRF2/SLC7A11/GPX4pathway being a key mechanism. This study contributes to a better understanding of COPD and airway inflammation, offering potential implications for the development of novel therapeutic strategies.