Calprotectin Levels Vary When Measured in Different Matrices for COVID-19

Several risk scores, diagnostic imaging and biomarkers have been evaluated and compared to help predict severe complications and outcome in COVID-19 patients. Nevertheless, early prediction of COVID-19 severity remains difficult, emphasizing the need for additional biomarkers in daily practice.

Calprotectin (CLP) is typically expressed and secreted by neutrophils, monocytes, and activated macrophages, but can also be expressed and secreted by other cell lines including but not limited to dendritic cells, endothelial cells, keratinocytes and squamous mucosal epithelium. Circulating CLP (cCLP) has gained recent attention as a biomarker of neutrophil-related inflammation and chronic inflammatory disorders.


Medical Laboratory Scientists at the OLV Hospital (Aalst, Belgium) prospectively included patients with primary diagnosis of SARS-CoV-2, confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR)) who presented at the emergency department (ED) requiring hospitalization. One hundred and thirty-six SARS-CoV-2 positive patients were included (70 hospitalized at a non-ICU ward; 66 at an ICU ward), next to 40 SARS-CoV-2 negative control patients (20 non-ICU; 20 CV-ICU).

The primary biomarkers of interest concerning the inflammatory response to COVID-19 were cCLP (measured in heparin, EDTA and citrate plasma and serum), C-reactive protein (CRP), Interleukin-6 (IL-6), lactate dehydrogenase (LDH) and procalcitonin (PCT). After routine laboratory analysis, including CRP, LDH and PCT analysis, was performed on blood samples taken at the ED, aliquots of serum, heparin plasma, EDTA plasma and citrate plasma were stored at -20 °C. Batch analyses of cCLP using the EliA Calprotectin 2 assay on a Phadia 200 instrument (Thermo Fisher Scientific, Waltham, MA, USA) and IL-6 (Elecsys IL-6 on cobas c801, Roche Diagnostics, Rotkreuz, Switzerland) were performed on stored aliquots.

The investigators reported that 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/extracorporeal membrane oxygenation (ECMO) (n=25), but iv) not in patients who deceased within 30 days (n=41).

The authors concluded that cCLP has a high power to discriminate severe or critical COVID-19 cases versus patients presenting with asymptomatic, mild or moderate disease, to predict the need for ICU admission and the need for mechanical ventilation or ECMO. The study was published on December 14, 2021 in the journal Clinica Chimica Acta.

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