Combining TMPRSS2 inhibitors with immune modulators, such as PD-1 inhibitors and/or JAK inhibitors, may offer a comprehensive approach for the treatment of COVID-19, but the therapeutic strategies need to be balanced between enhancing anti-viral immunity and preventing excessive inflammation and activation of the immune system, which can cause tissue damage and worsen outcomes as observed in severe COVID-19 cases. The gene discussed is PDCD1; the disease is COVID-19.