Circulating dipeptidyl peptidase 3 and bio-adrenomedullin levels are associated with impaired outcomes in critically ill COVID-19 patients: a prospective international multicentre study.

van Lier, Dirk;Deniau, Benjamin;Santos, Karine;Hartmann, Oliver;Pickkers, Peter;et.al.
(2023) ERJ Open Research — Vol. 9, n° 1, p. 00342-2022 [1-12] (2023)

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  • van Lier, Dirkorcid-logo
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  • Deniau, Benjamin
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  • Santos, Karine
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  • Hartmann, Oliver
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  • Laterre, Pierre-FrancoisUCLouvain
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  • Pickkers, Peter
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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. The objectives of the present study were to investigate associations of bio-ADM and "circulating DPP3" (cDPP3) with short-term outcome in critically ill COVID-19 patients (n=80). METHODS: A multicentre prospective cohort study was performed. The primary end-point was 28-day mortality. Secondary end-points included different severities of acute kidney injury (AKI). RESULTS: cDPP3 levels were mainly associated with 28-day mortality; Area under the receiver operating characteristics (AUROCs) 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, with AUROCs 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 (hazard ratio 11.8; 95% CI 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.
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van Lier, D., Deniau, B., Santos, K., Hartmann, O., Dudoignon, E., Depret, F., Plaud, B., Laterre, P.-F., Mebazaa, A., & Pickkers, P. (2023). Circulating dipeptidyl peptidase 3 and bio-adrenomedullin levels are associated with impaired outcomes in critically ill COVID-19 patients: a prospective international multicentre study. ERJ Open Research, 9(1), 00342-2022 [1-12]. https://doi.org/10.1183/23120541.00342-2022 (Original work published 2023)