Our results uncovered that gene networks of COVID-19 asymptomatic and sever samples involved in the “Systemic lupus erythematosus” pathway, while that of mild samples were associated with “Inflammatory bowel disease,” “Primary immunodeficiency pathways,” and “Rheumatoid arthritis.” The COVID-19 severity-specific gene network pathway analysis also revealed CXCL8 and S100A9 as crucial hub genes, and HLA class I (i.e. HLA-A, HLA-B, HLA-C) as the main player in the gene networks involved in immune disease pathways; these results have been validated in the literature. This evidence concerns the gene HLA-B and immune system disorder.