Our analysis revealed that the gene networks of COVID-19 asymptomatic and severe samples were enriched in “Systemic lupus erythematosus” pathway, whereas the network of mild samples was enriched in various immune disease pathways, such “Inflammatory bowel disease,” “Primary immunodeficiency,” and “Rheumatoid arthritis.” Our results also identified biomarkers of COVID-19, namely, CXCL8 and S100A9, as hub genes, as well as HLA class I, as the main players in the molecular interplay of COVID-19 severity-specific gene networks. Here, CXCL8 is linked to systemic lupus erythematosus.