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Proline-specific peptidase activities (DPP4, PRCP, FAP and PREP) in plasma of hospitalized COVID-19 patients
An Bracke1, Emilie De Hert1, Michelle De Bruyn1
1Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Belgium.
Insights
COVID-19 patients show altered levels of proline-selective peptidases, similar to sepsis. Dipeptidyl peptidase 4 (DPP4) and fibroblast activation protein alpha (FAP) decreased, while prolyl oligopeptidase (PREP) increased, suggesting a potential biomarker role.
Area of Science:
- Biochemistry
- Immunology
- Virology
Background:
- COVID-19 patients exhibit immune dysregulation mirroring sepsis.
- Previous research identified dysregulated proline-selective peptidases in sepsis.
- Key peptidases studied include dipeptidyl peptidase 4 (DPP4), fibroblast activation protein alpha (FAP), prolyl oligopeptidase (PREP), and prolylcarboxypeptidase (PRCP).
Purpose of the Study:
- To investigate if proline-selective peptidases are dysregulated in hospitalized COVID-19 patients.
- To compare peptidase activity changes in COVID-19 with those observed in sepsis.
Main Methods:
- Study included 56 hospitalized COVID-19 patients and 32 healthy controls.
- Enzymatic activities of DPP4, FAP, PREP, and PRCP were measured.
- Samples were collected at hospital admission and longitudinally during hospitalization.
Main Results:
- COVID-19 patients showed significantly lower DPP4 and FAP activities compared to controls.
- FAP activity further decreased within the first week of hospitalization.
- PREP activity was significantly increased at admission, rising further during hospitalization.
Conclusions:
- Plasma proline-selective peptidase changes in COVID-19 resemble those in septic shock.
- The significant decrease in FAP activity warrants further investigation for pathophysiological roles and biomarker utility.
Background:
COVID-19 patients experience several features of dysregulated immune system observed in sepsis. We previously showed a dysregulation of several proline-selective peptidases such as dipeptidyl peptidase 4 (DPP4), fibroblast activation protein alpha (FAP), prolyl oligopeptidase (PREP) and prolylcarboxypeptidase (PRCP) in sepsis. In this study, we investigated whether these peptidases are similarly dysregulated in hospitalized COVID-19 patients.
Methods:
Fifty-six hospitalized COVID-19 patients and 32 healthy controls were included. Enzymatic activities of DPP4, FAP, PREP and PRCP were measured in samples collected shortly after hospital admission and in longitudinal follow-up samples.
Results:
Compared to healthy controls, both DPP4 and FAP activities were significantly lower in COVID-19 patients at hospital admission and FAP activity further decreased significantly in the first week of hospitalization. While PRCP activity remained unchanged, PREP activity was significantly increased in COVID-19 patients at hospitalization and further increased during hospital stay and stayed elevated until the day of discharge.
Conclusion:
The changes in activities of proline-selective peptidases in plasma are very similar in COVID-19 and septic shock patients. The pronounced decrease in FAP activity deserves further investigation, both from a pathophysiological viewpoint and as its utility as a part of a biomarker panel.
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