This study was performed without the support or involvement of any external funding source or study sponsor in any phase of the investigation, or in the writing or submission of the manuscript. Consent to participateN/A. Consent to publishThe participants provided informed consent for publication. Human and animal rights disclosureN/A. Footnotes Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.. of the virus into the airway tract itself and could contribute to the development of cytokine storm and immunopathology in causing fatal COVID-19 pneumonia. Conclusions The use of DPP4 inhibitors, such as gliptins, in patients with COVID-19 with, or even without, type 2 diabetes, may offer a simple way to reduce the virus entry and replication into the airways and to hamper the sustained cytokine storm and inflammation within the lung in patients diagnosed with COVID-19 contamination. (sitagliptin in diabetic patients with COVID-19). Rabbit Polyclonal to OR10G4 is usually a caseCcontrol study, in which we will compare the clinical response of diabetic patients infected by COVID-19 during a 10?days course treatment with 100?mg Sitagliptin. Several data suggested that this latter immune pharmacological activity of DDP4 seems to be impartial of its catalytic activity  and for this reason unaffected by the use of inhibitors of the enzymatic activity of DPP4 . Other scientific evidences supported that the use of DPP4/CD26 inhibitors may act to antagonize airway inflammation . DPP4 inhibition by gliptins may antagonize SARSCCoV-2 virulence and multiorgan acute and chronic damage by means of several additive mechanisms that involve: (1) reduction of cytokines overproduction [12, 30, 38, 39]; (2) downregulation of macrophages activity/function ; (3) enhancement of GLP-1 anti-inflammatory activity [41, 42], particularly in those aged patients with COVID-19 ; (4) stimulation of direct pulmonary anti-inflammatory effects [44, 45]. In summary, we hypothesize (Fig.?1) that DPP4/CD26 inhibition with gliptins, and particularly with those with more highly selectivity for DPP4 [46, 47], could represent a new strategy to support the treatment of COVID-19 in patients with or without diabetes. Open in a separate window Fig.?1 Working hypothesis around the possible role of DPP4 inhibition (DPP4i) with gliptins to antagonize COVID-19 virulence and immunopathology Acknowledgements We thank the Fondazione Romeo and Enrica Invernizzi for the extraordinary support. Author contributions SBS, ADS, MG and PF designed and wrote the paper. All authors were given full access to all data presented in this study and are responsible for the integrity of the data and accuracy of the data analysis. GSK1278863 (Daprodustat) All authors have given their permission for submission of this manuscript. Funding Paolo Fiorina is usually supported by an Italian Ministry of Health Grant RF-2016-02362512 and by Linea-2 2019 funding from Universit di Milano. Paolo Fiorina is usually supported by Fondazione Romeo and Enrica Invernizzi. Availability of data and material All data generated or analyzed during this study are available from the corresponding author on affordable GSK1278863 (Daprodustat) request. Code availability Not applicable. Compliance with ethical standards Conflict of interestThe authors declare no present or potential conflicts of interest. This study was performed without the support or involvement of any external funding source or study sponsor in any phase of the investigation, or in the writing or submission of the manuscript. Consent to participateN/A. Consent to publishThe participants provided informed consent for publication. Human and animal rights disclosureN/A. Footnotes Publisher’s Note Springer Nature remains neutral with regard to jurisdictional GSK1278863 (Daprodustat) claims in published maps and institutional affiliations..