How Circulating Calprotectin Can Predict COVID-19 Severity

In these times of growing uncertainty, there is an unmet need that could improve our ability to defeat the COVID-19 virus: a biomarker with the ability to predict sudden and unexpected clinical deterioration and disease severity. This type of marker would enable medical professionals to screen the infected population, determine their expected disease risk, and intervene before further harm occurs. Recent research demonstrates how circulating calprotectin can predict COVID-19 severity.

Calprotectin is a protein that has historically been used as a biomarker of intestinal inflammation because it is released by neutrophils when they migrate to inflamed regions of the gastrointestinal tract. Recently, several studies have been published and referenced by Mahler et al. which suggest the use of circulating calprotectin as a biomarker for COVID-19 severity. The key findings of each of these studies are summarized in Table 1.

Overall, the studies found there was an increased concentration of circulating calprotectin in people with COVID-19 versus their healthy counterparts. The difference was especially significant in differentiating the intensity of cases, with comparisons made between mild vs. severe cases and survivors vs. non-survivors.

While this research presents a promising outlook on the use of circulating calprotectin as a biomarker for COVID-19 risk, some limitations were mentioned by Mahler et al. In most of the studies, the population of subjects was small, and there was an imbalance between the groups being compared (controls vs. sick individuals, survivors vs. non-survivors). Further, the circulating calprotectin values were evaluated using different assays.

The discovery of circulating calprotectin as a potential biomarker for COVID-19 severity could drastically improve our ability to defeat the virus. The results of 11 studies showed that circulating calprotectin concentration differed between varying levels of COVID-19 risk; demonstrating that individuals with more severe cases can have higher concentrations of calprotectin. From these findings, it may be possible to use an individual’s circulating calprotectin concentration as a marker to predict the intensity of their immune response to the COVID-19 virus and to better protect at-risk individuals.

Table 1 outlines recent research demonstrating how circulating calprotectin can help predict COVID-19 severity.

Interested in adding calprotectin to your lab’s immunoassay offerings? Check out our calprotectin ELISAs, offered in individual or bulk quantities.

No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.


  1. Mahler, Michael, et al. “Circulating CALPROTECTIN as a Biomarker of COVID-19 SEVERITY.” Expert Review of Clinical Immunology, vol. 17, no. 5, 2021, pp. 431–443., doi:10.1080/1744666x.2021.1905526.
  2.  Abers, Michael S., et al. “An Immune-Based Biomarker Signature Is Associated with Mortality in COVID-19 Patients.”JCI Insight, vol. 6, no. 1, 2021, doi: 10.1172/jci.insight.144455.
  3. Bauer, Wolfgang, et al. “Outcome Prediction by Serum Calprotectin in Patients with COVID-19 in the Emergency Department.”Journal of Infection, vol. 82, no. 4, 17 Nov. 2020, pp. 84–123., doi: 10.1016/j.jinf.2020.11.016.
  4. Chen, Liting, et al. “Elevated Serum Levels of S100A8/A9 and HMGB1 at Hospital Admission Are Correlated with Inferior Clinical Outcomes in COVID-19 Patients.” Cellular & Molecular Immunology, vol. 17, no. 9, 2020, pp. 992–994., doi: 10.1038/s41423-020-0492-x.
  5. De Guadiana Romualdo, Luis García, et al. “Circulating Levels of GDF-15 and Calprotectin for Prediction of in-Hospital Mortality in COVID-19 Patients: A Case Series.”Journal of Infection, vol. 82, no. 2, 12 Aug. 2020, doi: 10.1016/j.jinf.2020.08.010.
  6. Kaya, Tezcan, et al. “Serum Calprotectin as a Novel Biomarker for Severity of Covid-19 Disease.” Irish Journal of Medical Science (1971 -), 27 Feb. 2021, doi: 10.1007/s11845-021-02565-8.
  7. Shaath, Hibah, et al. “Single-Cell Transcriptome Analysis Highlights a Role for Neutrophils and Inflammatory Macrophages in the Pathogenesis of Severe COVID-19.” Cells, vol. 9, no. 11, 29 Oct. 2020, p. 2374., doi: 10.3390/cells9112374.
  8. Shi, Hui, et al. “Neutrophil Calprotectin Identifies Severe Pulmonary Disease in Covid-19.” J Leukoc Biol., vol. 109, no. 1, Jan 2021, pp. 67-72, doi: 10.1002/JLB.3COVCRA0720-359R.
  9. Shu, Ting, et al. “Plasma Proteomics Identify Biomarkers and Pathogenesis of COVID-19.”Immunity, vol. 53, no. 5, 10 Oct. 2020, doi: 10.1016/j.immuni.2020.10.008.
  10. Silvin, Aymeric, et al. “Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19.” Cell, vol. 182, no. 6, 5 Aug. 2020, doi: 10.1016/j.cell.2020.08.002.
  11. Sohn, KyungMok, et al. “COVID-19 Patients Upregulate Toll-like Receptor 4-Mediated Inflammatory Signaling That Mimics Bacterial Sepsis.” Journal of Korean Medical Science, vol. 35, no. 38, 28 Sept. 2020, doi: 10.3346/jkms.2020.35.e343.
  12. Wu, Meng, et al. “Transcriptional and Proteomic Insights into the Host Response in Fatal Covid-19 Cases.” Proceedings of the National Academy of Sciences, vol. 117, no. 45, 20 Nov. 2020, pp. 28336–28343., doi: 10.1073/pnas.2018030117.

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