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Diabetologie und Stoffwechsel ; 17:S54, 2022.
Article in English | EMBASE | ID: covidwho-1967654


Background and Aim Obesity and type 2 diabetes (T2D) show an increased risk for a severe COVID-19 disease. Treatment with DPP4 inhibitor (DPP4i) results in reduced mortality and better clinical outcome. Here, we aimed to identify potential mechanisms for the observed DPP4i effect in COVID-19. Methods We compared T2D subjects with (cases) and without (controls) DPP4i treatment (N=69), as well as patients hospitalised for severe COVID-19 and healthy controls (N=34) with regard to serum concentrations of soluble frizzle receptor protein 5 (sFRP5) using univariate statistics. Furthermore, we isolated pre-adipocytes, mature adipocytes and macrophages from adipose tissue biopsies (N=100) and performed western-blotting for sFRP5 and Wnt5a expression. Results In T2D patients, we identified a significant increase of the anti-inflammatory adipokine sFRP5 in relation to DPP4 inhibition. sFRP5 is a specific antagonist to Wnt5a, a glycopeptide secreted by adipose tissue macrophages acting proinflammatory in various diseases. We therefore examined sFRP5 levels in patients hospitalised for severe COVID-19 and found significant lower levels compared to healthy controls. Since sFRP5 might consequently be a molecular link for the beneficial effects of DPP4i in COVID-19, we further aimed to identify the exact source of sFRP5 in adipose tissue on cellular level. Results from western-blotting in adipose tissues showed a sFRP5 expression specifically in mature adipocytes of subcutaneous and omental adipose tissue. Conclusion In summary, our data suggest that DPP4i increase serum levels of anti-inflammatory sFRP5 which might be beneficial in COVID-19, reflecting a state of sFRP5 deficiency.

Diabetologie und Stoffwechsel ; 16(SUPPL 1):S70-S71, 2021.
Article in English | EMBASE | ID: covidwho-1284744


Aims Dipeptidylpeptidase is a key regulator of the incretin system. Initially, it's soluble form (sDPP-4) was described as an adipokine mediating metabolic inflammation. This is recently questioned in mechanistic rodent studies. To further clarify sDPP-4's role in physiology and metabolic diseases, we examined sDPP-4 in a large human cohort and during weight-loss interventions. Like ACE2, sDPP-4 serves as a binding partner for certain corona-like viruses enabling virus entry. As metabolic diseases are major risk factors for the COVID-19 pandemic, we additionally examined sDPP-4 in patients suffering severe Sars-CoV-2 infection. Methods sDPP-4 serum concentrations were measured using ELISA and related to various metabolic variables. Using a case-control-design, sDPP-4 was assessed in acute COVID-19 and sepsis infection. Results sDPP-4 increased with body weight, insulin resistance and hypertriglyceridemia but reduced in type 2 diabetes and arterial hypertension. Altered serum concentrations appeared with impaired liver and kidney but not cardiac function. No association to systemic inflammation was observed. Having found increased sDPP-4 in obesity, surgical (gastric bypass/sleeve gastrectomy) and non-surgical weight-loss interventions revealed a significant association of sDPP-4 with the improvement of liver function but neither with changes in body weight nor fat mass. Complementary, the case control study revealed reduced sDPP-4 concentrations specific for COVID-19 infection. Conclusions We suggest that sDPP-4 is rather related to hepatic abnormalities in obesity than primarily functioning as an adipokine. sDPP-4 is implicated in glucose and lipid metabolism, but not fundamentally in systemic inflammation. Additional to ACE-2, sDPP-4 might also have a regulatory role in COVID-19 infection.

Monatsschr Kinderheilkd ; 168(7): 615-627, 2020.
Article in German | MEDLINE | ID: covidwho-174910


BACKGROUND: The clinical knowledge about the course, complications and treatment of COVID-19 in children and adolescents is so far limited. AIM: This systematic review summarizes the current scientific evidence regarding the clinical presentation of COVID-19 in hospitalized children based on available case series from China. In addition, first data from a nationwide pediatric hospital survey conducted by the German Society for Pediatric Infectious Diseases (DGPI) are presented. METHODS: This study evaluated 12 case series from China with 6-2143 children infected with SARS-CoV­2, which were identified by a literature search in PubMed up to 31 March 2020. The database of the German nationwide DGPI COVID-19 survey was accessed on 6 April 2020. RESULTS: The median patient age in the case series was between 2 and 7 years and 18-45% were infants <1 year of age. The duration of hospital stay was 5-20 days. Most commonly reported symptoms were fever and cough; in 40-100% of cases involvement of the lower respiratory tract was reported, usually confirmed by computed tomography (CT). Severe and critical courses of disease were reported in up to 8% of the children including 2 fatalities. So far the German DGPI COVID-19 survey reported 33 hospitalized children up to 6 April 2020, mostly with upper airway infections. Of these children, 45% were infants and 32% had an underlying medical condition. So far 3 children (9%) needed admission to an intensive care unit. CONCLUSION: COVID-19 in hospitalized children usually presented as an uncomplicated febrile upper airway infection or mild pneumonia. Severe cases or fatalities rarely occurred in children. Information on neonates and children with underlying chronic conditions as well as on therapeutic and preventive measures are urgently needed.