Neutrophil calprotectin identifies severe pulmonary disease in COVID-19

J Leukoc Biol. 2021 Jan;109(1):67-72. doi: 10.1002/JLB.3COVCRA0720-359R. Epub 2020 Sep 1.


Severe cases of coronavirus disease 2019 (COVID-19) are regularly complicated by respiratory failure. Although it has been suggested that elevated levels of blood neutrophils associate with worsening oxygenation in COVID-19, it is unknown whether neutrophils are drivers of the thrombo-inflammatory storm or simple bystanders. To better understand the potential role of neutrophils in COVID-19, we measured levels of the neutrophil activation marker S100A8/A9 (calprotectin) in hospitalized patients and determined its relationship to severity of illness and respiratory status. Patients with COVID-19 (n = 172) had markedly elevated levels of calprotectin in their blood. Calprotectin tracked with other acute phase reactants including C-reactive protein, ferritin, lactate dehydrogenase, and absolute neutrophil count, but was superior in identifying patients requiring mechanical ventilation. In longitudinal samples, calprotectin rose as oxygenation worsened. When tested on day 1 or 2 of hospitalization (n = 94 patients), calprotectin levels were significantly higher in patients who progressed to severe COVID-19 requiring mechanical ventilation (8039 ± 7031 ng/ml, n = 32) as compared to those who remained free of intubation (3365 ± 3146, P < 0.0001). In summary, serum calprotectin levels track closely with current and future COVID-19 severity, implicating neutrophils as potential perpetuators of inflammation and respiratory compromise in COVID-19.

Keywords: COVID-19; SARS-CoV-2; calprotectin; neutrophil extracellular traps; neutrophils.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • COVID-19* / blood
  • COVID-19* / immunology
  • COVID-19* / pathology
  • COVID-19* / therapy
  • Calgranulin A* / blood
  • Calgranulin A* / immunology
  • Calgranulin B* / blood
  • Calgranulin B* / immunology
  • Female
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Neutrophil Activation*
  • Neutrophils* / immunology
  • Neutrophils* / metabolism
  • Neutrophils* / pathology
  • SARS-CoV-2* / immunology
  • SARS-CoV-2* / metabolism
  • Severity of Illness Index
  • Time Factors


  • Calgranulin A
  • Calgranulin B
  • S100A8 protein, human
  • S100A9 protein, human