Prognostic value of circulating calprotectin levels on the clinical course of COVID-19 differs between serum, heparin, EDTA and citrate sample types

•cCLP can help clinicians to predict the clinical course of COVID-19.•The discriminatory power of EDTA and citrate plasma cCLP levels is often superior.•Be aware of variations in cCLP levels when measured in different matrices. During the recent SARS-CoV-2 pandemic, circulating calprotectin (cCLP) gained interest as biomarker to predict the severity of COVID-19. We aimed to investigate the prognostic value of cCLP measured in serum, heparin, EDTA and citrate plasma. COVID-19 patients were prospectively included, in parallel with two SARS-CoV-2 negative control populations. The prognostic value of cCLP was compared with IL-6, CRP, LDH, procalcitonin, and the 4C-mortality score by AUROC analysis. For the 136 COVID-19 patients, cCLP levels were higher compared to the respective control populations, with significantly higher cCLP levels in serum and heparin than in EDTA or citrate. Higher cCLP levels were obtained for COVID-19 patients with i) severe/critical illness (n = 70), ii) ICU admission (n = 66) and iii) need for mechanical ventilation/ECMO (n = 25), but iv) not in patients who deceased within 30 days (n = 41). The highest discriminatory power (AUC [95% CI]) for each defined outcome was i) CRP (0.835 [0.755–0.914]); ii) EDTA cCLP (0.780 [0.688–0.873]); iii) EDTA cCLP (0.842 [0.758–0.925]) and iv) the 4C-mortality score (0.713 [0.608–0.818]). Measuring cCLP in COVID-19 patients helps the clinician to predict the clinical course of COVID-19. The discriminatory power of EDTA and citrate plasma cCLP levels often outperforms heparin plasma cCLP levels.