Circulating levels of soluble Dipeptidylpeptidase-4 are reduced in human subjects hospitalized for severe COVID-19 infections

• Published in: International Journal of Obesity Vol. 44; no. 11; pp. 2335 - 2338
• Main Authors: Schlicht, Kristina, Rohmann, Nathalie, Geisler, Corinna, Hollstein, Tim, Knappe, Carina, Hartmann, Katharina, Schwarz, Jeanette, Tran, Florian, Schunk, Domagoj, Junker, Ralf, Bahmer, Thomas, Rosenstiel, Philip, Schulte, Dominik, Türk, Kathrin, Franke, Andre, Schreiber, Stefan, Laudes, Matthias
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2020; Nature Publishing Group
• Subjects: 13/1; 631/45/607; 692/499; 692/699/2743/137/773; 692/699/2743/393; 96/1; Aged; Betacoronavirus; Binding; Case-Control Studies; Comment; Coronavirus Infections - blood; Coronavirus Infections - epidemiology; Coronaviruses; COVID-19; Data points; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes therapy; Dipeptidyl Peptidase 4 - blood; Dipeptidyl-peptidase IV; Epidemiology; Female; Health aspects; Health Promotion and Disease Prevention; Hospitalization; Human subjects; Humans; Immune system; Infections; Internal Medicine; Internalization; Male; Medicine; Medicine & Public Health; Membranes; Metabolic Diseases; Metabolic disorders; Middle Aged; Obesity; Pandemics; Pneumonia, Viral - blood; Pneumonia, Viral - epidemiology; Proteases; Public Health; Risk analysis; Risk factors; SARS-CoV-2; Sepsis; Sepsis - blood; Sepsis - epidemiology; Type 2 diabetes; Viral diseases; Virus diseases; Viruses
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/s41366-020-00689-y

Dipeptidylpeptidase (DPP)-4 is a key regulator of the incretin system. For several years DPP-4 inhibitors in addition to GLP-1 analogues are of major importance in the clinical management of obesity and type 2 diabetes. DPP-4 is also known as CD26 and represents a membrane bound protease on the surface of several eukaryotic cell types. Of interest, DPP-4, like ACE2, has been shown to serve as a binding partner for corona-like viruses to enter host immune cells. Since metabolic diseases are major risk factors for the present COVID-19 pandemic, we examined circulating soluble DPP-4 serum concentrations in patients suffering from severe COVID-19 infection and in healthy human subjects in a case control design. In this analysis sDPP-4 levels were significantly lower in COVID-19 patients compared to controls (242.70 ± 202.12 ng/mL versus 497.70 ± 188.13 ng/mL, p = 0.02). We also examined sDPP-4 serum concentrations in patients suffering from sepsis not due to corona-like viruses. In these subjects, sDPP-4 levels were not different compared to healthy case controls (p = 0.14), which might suggest the decrease of sDPP-4 to be specific for corona-like virus infections. Currently, most data point towards membrane bound ACE2 in contrast to DPP-4 as the major binding partner for COVID-19 internalization into host immune cells. However, the finding that the circulating soluble form of DPP-4 is reduced in hospitalized patients might suggest a regulatory role for both, ACE and DPP-4, in COVID-19 infections, especially since obesity and type 2 diabetes are major risk factor for a severe course of the disease