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

Abstract

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 * Matthias Laudes

DPP4 Inhibitors and COVID-19–Holy Grail or Another Dead End?

“…Unexpectedly, in patients infected with MERS-CoV, the concentration of sDPP4 in plasma was significantly decreased and correlated with disease severity (Inn et al 2018 ; Zhao et al 2020 ). Recently, similar observation was reported in patients with severe course of COVID-19 (Schlicht et al 2020 ). However, it is unclear, whether sDPP4 reduction was a simple effect of lymphopenia, which is typical for patients infected with novel coronaviruses, or should rather be considered as an initial condition and presumable cause of increased susceptibility to MERS-CoV or SARS-CoV-2 infection.…”

The Association Between Hypoglycemic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis

“…As DPP-4 is hypothesized to be a binding partner for corona-like viruses to enter host immune cells, DPP-4i also exerts influence on prohibiting invasion of SARS-CoV-2 into cells (49). However, concentration of circulating soluble DPP-4 serum in patients suffering from severe was significantly lower compared to that in healthy human subjects (50), which contradicts the protective effects of DPP-4i. Sitagliptin, a DPP-4i drug, was thought to have anti-inflammatory effects on diabetic patients via the NF-kappa-B signaling pathway (51).…”

Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning

“…Nevertheless, experimental data do not support and actually refute the contention that human recombinant DPP-4 binds SARS-CoV-2 ( Xi et al., 2020 ). Serum circulating levels of sDPP-4 were reduced by ~50% in 7 individuals hospitalized with COVID-19 ( Schlicht et al., 2020 ); however, given the substantial intra- and inter-individual variability of sDPP-4 in humans, this preliminary observation must be confirmed in larger datasets ( Baggio et al., 2020 ).…”