Insulin may promote SARS-CoV-2 cell entry and replication in diabetes patients

Patients with diabetes often have severe hyperglycemia triggered by novel coronavirus disease 2019 (COVID-19). Insulin treatment should be the main approach to the control of acute hyperglycemia in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, clinical investigation found that insulin treatment is associated with a significant increase in mortality risk in patients with diabetes and SARS-CoV-2 infection. The reason for this high mortality rate remains obscure. Previous studies have demonstrated that insulin is an activator of Na⁺/H⁺ exchanger (NHE) which could decrease extracellular pH and increase intracellular pH and glycolysis. Here, the author emphasizes insulin may contribute to SARS-CoV-2 cell entry and multiplication in host cells through activation of Na⁺/H⁺ exchange. Additionally, the inhibition of Na⁺ /H⁺ exchange activity or glycolytic flux can result in reduced mortality in patients with COVID-19 and diabetes mellitus during insulin treatment.