RT Journal Article
SR Electronic
T1 Circulating dipeptidyl peptidase 3 and bio-adrenomedullin levels are associated with impaired outcomes in critically ill COVID-19 patients: a prospective international multicentre study
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00342-2022
DO 10.1183/23120541.00342-2022
A1 van Lier, Dirk
A1 Deniau, Benjamin
A1 Santos, Karine
A1 Hartmann, Oliver
A1 Dudoignon, Emmanuel
A1 Depret, François
A1 Plaud, Benoit
A1 Laterre, Pierre-Francois
A1 Mebazaa, Alexandre
A1 Pickkers, Peter
YR 2022
UL http://openres.ersjournals.com/content/early/2022/10/06/23120541.00342-2022.abstract
AB Introduction Dipeptidyl-peptidase-3 (DPP3) is a protease involved in the degradation of several cardiovascular mediators. Adrenomedullin (bio-ADM) is a peptide essential for regulation of endothelial barrier function. In different shock-pathologies, both biomarkers are associated with disease-severity, organ dysfunction and mortality. Associations with outcome in critically ill COVID-19 patients are unknown.Objectives To investigate associations of bio-ADM and cDPP3 with short-term outcome in critically ill COVID-19 patients (n=80).Methods Multicenter prospective cohort study. Primary endpoint was 28-day mortality. Secondary endpoints included different severities of acute kidney injury (AKI).Results cDPP3 levels were mainly associated with 28-day mortality; AUROC's of 0.69 (0.56–0.82, p=0.023), 0.77 (0.64–0.90, p<0.001) and 0.81 (0.65–0.96, p<0.001) at admission, day 3 and day 7, respectively. In contrast, bio-ADM levels were mainly associated with AKI: AUROC's of 0.64 (0.51–0.77, p=0.048), 0.75 (0.64–0.86, p<0.001) and 0.83 (0.74–0.93, p<0.001) for day 1, 3 and 7, respectively. Interestingly, patients with high levels of both cDPP3 and bio-ADM at day 7 had an additionally increased risk of 28-day-mortality; HR 11.8 (2.5–55.3, p<0.001).Conclusions cDPP3 and bio-ADM responses were associated with short-term mortality and AKI in critically ill COVID-19 patients, respectively. These findings suggest that treatment with specific antibodies modulating cDPP3 or bio-ADM related pathways may improve outcome of COVID-19.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Analyses of samples was performed free of charge by the respective biomarker companies (Sphingotec for bio-ADM, 4TEEN4 for cDPP3). No additional funding was provided for the execution of this study. Both biomarker-companies had no role in the design of the study, it's execution, analyses, interpretation of the data, as well as the decision to submit results.Conflict of interest: Dirk van Lier was invited to a meeting in Berlin by 4TEEN4 Pharmaceuticals GmbH.Conflict of interest: Benjamin Deniau was invited to a meeting in Henningsdorf by 4TEEN4 Pharmaceuticals GmbH.Conflict of interest: Karine Santos is employed by 4TEEN4 Pharmaceuticals, the company holding patent rights for the DPP3 assay.Conflict of interest: Oliver Hartmann is employed by Sphingotec GmbH, the company holding patent rights for the bio-ADM assay and a licence to commercialise the cDPP3 assay.Conflict of interest: Emmanuel Dudoignon has nothing to declare.Conflict of interest: François Depret has nothing to declare.Conflict of interest: Benoit Plaud has nothing to declareConflict of interest: Pierre-Francois Laterre received travel and consultancy reimbursements from 4TEEN4 and Sphingotec, the companies holding patent rights for the DPP3 and bio-ADM assays used in the study, respectively.Conflict of interest: Alexandre Mebazaa received travel and consultancy reimbursements from 4TEEN4 and Sphingotec, the companies holding patent rights for the DPP3 and bio-ADM assays used in the study, respectively.Conflict of interest: Peter Pickkers received travel and consultancy reimbursements from 4TEEN4 and Sphingotec, the companies holding patent rights for the DPP3 and bio-ADM assays used in the study, respectively.