Calprotectin as an early marker to prevent sepsis

13. Sep 2021 | 13 min read

Calprotectin as an early marker to prevent sepsis

Sepsis Awareness Month and World Sepsis Day

September is sepsis awareness month, and the 10th World Sepsis Day, an initiative by the Global Sepsis Alliance (GSA), is held on 13th September 2021.


Sepsis awareness and prevention

Sepsis is the leading cause of death among critically ill patients in intensive care units (ICU), with a continuously increasing incidence and a high mortality rate.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. It arises when the body’s response to an infection (bacterial, fungal or viral) starts to injure its own tissues and organs. If this response is not recognised early and treated promptly it might lead to septic shock with multi-organ failure and death. You can find more information about sepsis at


Biomarkers for early detection 

Early detection and intervention are critical to prevent the development of sepsis and severe events, as it is the most common cause of death in critically ill patients1.

Calprotectin is one of the earliest biomarkers for detection of the inflammatory response to infections2,3. The biomarker is predominantly expressed in neutrophil granulocytes, and it is released upon neutrophil activation in response to inflammation and infection.

Calprotectin’s benefits have been linked to the assessment of sepsis as the biomarker shows early diagnostic and predictive value4-10. In addition, calprotectin also gradually increases with disease severity in septic patients3,5. High calprotectin levels can be predictive for disease severity and clinical course of septic patients6,7 as well as mortality5,7-9 and can also improve classical risk scoring8. Early assessment is important to prevent sepsis, and calprotectin's predictive value can therefore play an important role.

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Sepsis in COVID-19

SARS-CoV-2 has been described to cause viral sepsis11-17, and the reported diagnostic value of calprotectin in SARS-CoV-2 infection is related to the hyperinflammatory response in severe COVID-19 leading to viral sepsis14-25.

Neutrophils are upregulated and activated in COVID-19 patients as potential driver of disease severity26-28. Hospitalised COVID-19 patients with severe form of the disease show dysregulated immune response and induction of cytokine response (also called cytokine storm or hyperinflammation), which is a reaction very similar to bacterial sepsis15, 28-31.

Following the pathology of neutrophil activation and hyperinflammation in COVID-19, it is conceivable that calprotectin is a sensitive risk marker both in the viral infection resulting in severe COVID-19 and bacterial infections. Calprotectin’s diagnostic value lies within an early risk assessment and prediction of severe events and thereby aid to prevent the development sepsis.

You can learn more about sepsis in COVID-19 in the article: FAQ: Why is calprotectin upregulated in COVID-19?.




plasma and serum calprotectin



  1. Singer M et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)JAMA. 2016 
  2. Fullerton J et al. Kinetics of calprotectin, procalcitonin and C-reactive protein in healthy volunteers administered intravenous endotoxin. 40th International Symposium on Intensive Care & Emergency Medicine. Critical Care. 2020. P474
  3. Jonsson N et al. Calprotectin as an early biomarker of bacterial infections in critically ill patients: an exploratory cohort assessmentCrit Care Resusc. 2017
  4. Bartáková E et al. Calprotectin and calgranulin C serum levels in bacterial sepsisDiagn Microbiol Infect Dis. 2019
  5. Gao S et al. Diagnostic and prognostic value of myeloid-related protein complex 8/14 for sepsisAm J Emerg Med. 2015
  6. Parke Å et al. Plasma-calprotectin compared with routine biomarkers for prediction of early severe event in sepsis. 40th International Symposium on Intensive Care & Emergency Medicine. Critical Care. 2020. 477
  7. Wirtz TH et al. Association of Serum Calprotectin Concentrations with Mortality in Critically Ill and Septic PatientsDiagnostics (Basel). 2020
  8. Dubois C et al. High plasma level of S100A8/S100A9 and S100A12 at admission indicates a higher risk of death in septic shock patientsSci Rep. 2019
  9. Larsson A et al. Calprotectin is superior to procalcitonin as a sepsis marker and predictor of 30-day mortality in intensive care patients. Scand J Clin Lab Invest. 2020
  10. Huang L et al. Serum Calprotectin Expression as a Diagnostic Marker for Sepsis in Postoperative Intensive Care Unit PatientsJ Interferon Cytokine Res. 2016
  11. Vincent JL. COVID-19: it's all about sepsisFuture Microbiol. 2021
  12. Odabasi Z, Cinel I. Consideration of Severe Coronavirus Disease 2019 As Viral Sepsis and Potential Use of Immune Checkpoint InhibitorsCrit Care Explor. 2020
  13. Global Sepsis Alliance
  14. Shappell CN et al. Does Severe Acute Respiratory Syndrome Coronavirus 2 Cause Sepsis?Crit Care Med. 2020
  15. Li H et al. SARS-CoV-2 and viral sepsis: observations and hypothesesLancet. 2020
  16. López-Collazo E et al. Immune Response and COVID-19: A mirror image of SepsisInt J Biol Sci. 2020
  17. Liu D et al. Viral sepsis is a complication in patients with Novel Corona Virus Disease (COVID-19)Med Drug Discov. 2020
  18. Luis García de Guadiana Romualdo et al. Circulating levels of GDF-15 and calprotectin for prediction of in-hospital mortality in COVID-19 patients: A case seriesJ Infect. 2021
  19. Shi H et al. Neutrophil calprotectin identifies severe pulmonary disease in COVID-19J Leukoc Biol. 2021
  20. Chen L et al. Elevated serum levels of S100A8/A9 and HMGB1 at hospital admission are correlated with inferior clinical outcomes in COVID-19 patientsCell Mol Immunol. 2020
  21. Udeh R et al. Calprotectin, an Emerging Biomarker of Interest in COVID-19: A Systematic Review and Meta-AnalysisJ Clin Med. 2021
  22. Shu T et al. Plasma Proteomics Identify Biomarkers and Pathogenesis of COVID-19Immunity. 2020
  23. Silvin A et al. Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19Cell. 2020
  24. Bauer W et al. Outcome prediction by serum calprotectin in patients with COVID-19 in the emergency departmentJ Infect. 2021
  25. Giuffrè M et al. Calprotectin and SARS-CoV-2: A Brief-Report of the Current LiteratureHealthcare (Basel). 2021
  26. Zuo Y et al. Neutrophil extracellular traps in COVID-19JCI Insight. 2020
  27. Barnes BJ et al. Targeting potential drivers of COVID-19: Neutrophil extracellular trapsJ Exp Med. 2020
  28. Guo Q et al. Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19Cell Host Microbe. 2021
  29. Beltrán-García J et al. Sepsis and Coronavirus Disease 2019: Common Features and Anti-Inflammatory Therapeutic ApproachesCrit Care Med. 2020
  30. Sohn KM et al. COVID-19 Patients Upregulate Toll-like Receptor 4-mediated Inflammatory Signaling That Mimics Bacterial SepsisJ Korean Med Sci. 2020
  31. Wilson JG et al. Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsisJCI Insight. 2020



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