Abstract
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.
Footnotes
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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 declare
Conflict 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.
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- Received July 11, 2022.
- Accepted October 4, 2022.
- Copyright ©The authors 2022
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