Identification of Age-Related Characteristic Genes Involved in Severe COVID-19 Infection Among Elderly Patients Using Machine Learning and Immune Cell Infiltration Analysis.

Journal: Biochemical genetics
Published Date:

Abstract

Elderly patients infected with severe acute respiratory syndrome coronavirus 2 are at higher risk of severe clinical manifestation, extended hospitalization, and increased mortality. Those patients are more likely to experience persistent symptoms and exacerbate the condition of basic diseases with long COVID-19 syndrome. However, the molecular mechanisms underlying severe COVID-19 in the elderly patients remain unclear. Our study aims to investigate the function of the interaction between disease-characteristic genes and immune cell infiltration in patients with severe COVID-19 infection. COVID-19 datasets (GSE164805 and GSE180594) and aging dataset (GSE69832) were obtained from the Gene Expression Omnibus database. The combined different expression genes (DEGs) were subjected to Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Diseases Ontology functional enrichment analysis, Gene Set Enrichment Analysis, machine learning, and immune cell infiltration analysis. GO and KEGG enrichment analyses revealed that the eight DEGs (IL23A, PTGER4, PLCB1, IL1B, CXCR1, C1QB, MX2, ALOX12) were mainly involved in inflammatory mediator regulation of TRP channels, coronavirus disease-COVID-19, and cytokine activity signaling pathways. Three-degree algorithm (LASSO, SVM-RFE, KNN) and correlation analysis showed that the five DEGs up-regulated the immune cells of macrophages M0/M1, memory B cells, gamma delta T cell, dendritic cell resting, and master cell resisting. Our study identified five hallmark genes that can serve as disease-characteristic genes and target immune cells infiltrated in severe COVID-19 patients among the elderly population, which may contribute to the study of pathogenesis and the evaluation of diagnosis and prognosis in aging patients infected with severe COVID-19.

Authors

  • Huan Li
    National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
  • Jin Zhao
    Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, 36 Lazi East Road, Tianfu New Area, Chengdu, 610000, China.
  • Yan Xing
    School of science, China Pharmaceutical University, Nanjing, China.
  • Jia Chen
    Department of Oncology Internal Medicine, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, Nantong, China.
  • Ziying Wen
    Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, No. 127 Chang Le West Road, Xi'an, 710032, Shaanxi, China.
  • Rui Ma
    Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, China.
  • Fengxia Han
    Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, No. 127 Chang Le West Road, Xi'an, 710032, Shaanxi, China.
  • Boyong Huang
    Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, No. 127 Chang le West Road, Xi'an, 710032, Shaanxi, China.
  • Hao Wang
    Department of Cardiology, Second Medical Center, Chinese PLA General Hospital, Beijing, China.
  • Cui Li
    College of Veterinary Medicine, Northwest A&F University Yangling, China.
  • Yang Chen
    Orthopedics Department of the First Affiliated Hospital of Tsinghua University, Beijing, China.
  • Xiaoxuan Ning
    Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, No. 127 Chang Le West Road, Xi'an, 710032, Shaanxi, China. ningxx01@fmmu.edu.cn.