Reducing metabolic stress by pharmacological and lifestyle interventions effectively lowers the expression of GRP78 and may be helpful for improving COVID-19 symptom; Anti-diabetic drugs, such as metformin and SGLT2 inhibitor, or lifestyle changes, such as calorie restriction and exercise, reduced the expressions of GRP78 in adipose tissues [12]; appropriate control of metabolic abnormalities by diabetic drugs may improve the severe outcomes of COVID-19 [12,94]. The gene discussed is HSPA5; the disease is COVID-19.