Circulating levels of calprotectin, a signature of neutrophil activation in prediction of severe respiratory failure in COVID-19 patients: a multicenter, prospective study (CalCov study)

Inflamm Res. 2022 Jan;71(1):57-67. doi: 10.1007/s00011-021-01516-4. Epub 2021 Oct 30.


Objective: Severe COVID-19 is characterized by a dysregulated immune response in which neutrophils play a critical role. Calprotectin reflects neutrophil activation and is involved in the self-amplifying thrombo-inflammatory storm in severe COVID-19. We aimed to evaluate the role of calprotectin in early prediction of severity in COVID-19 patients.

Methods: This was a multicenter prospective observational study enrolling consecutive adult COVID-19 patients. On arrival to emergency department, blood samples were collected for laboratory tests, including serum calprotectin. The primary outcome was severe respiratory failure requiring invasive mechanical ventilation and the secondary outcome was need for Intensive Care Unit (ICU) admission.

Results: Study population included 395 patients, 57 (14.4%) required invasive mechanical ventilation and 100 (25.3%) were admitted to ICU. Median serum calprotectin levels were significantly higher in intubated (3.73 mg/L vs. 2.63 mg/L; p < 0.001) and ICU patients (3.48 mg/L vs. 2.60 mg/L; p = 0.001). Calprotectin showed a significant accuracy to predict the need for invasive mechanical ventilation (ROC AUC 0.723) and ICU admission (ROC AUC 0.650). In multivariate analysis, serum calprotectin was an independent predictor of invasive mechanical ventilation (OR 1.161) and ICU admission (OR 1.068).

Conclusion: Serum calprotectin can be used as an early predictor of severity in COVID-19 patients.

Keywords: COVID-19; Calprotectin; ICU admission; Invasive mechanical ventilation; Neutrophil activation.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • COVID-19 / blood*
  • COVID-19 / complications
  • COVID-19 / diagnosis*
  • Female
  • Humans
  • Immune System
  • Inflammation
  • Intensive Care Units
  • Leukocyte L1 Antigen Complex / blood*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neutrophil Activation*
  • Neutrophils / cytology*
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • Respiration, Artificial*
  • Respiratory Insufficiency / complications
  • Respiratory Insufficiency / diagnosis*
  • Treatment Outcome
  • Young Adult


  • Leukocyte L1 Antigen Complex