Blocking the cytokine–receptor axes, such as CCL2-CCR2, CCL3-CCR1, CCL3-CCR5, CCL4-CCR5, CCL3L1-VSIR, and CCL3L1-CCR1, may be a novel strategy to reverse TEX and furhter to treat severe COVID-19 with cytokine storm-related immune exhaustion. The gene discussed is CCR5; the disease is COVID-19.