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Meta-Analysis
. 2024 Mar;12(3):e1212.
doi: 10.1002/iid3.1212.

Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID-19

Haoran Zhang  1 , Qingyu Zhang  1 , Kun Liu  2 , Zenong Yuan  1 , Xiqiang Xu  1 , Jun Dong  1
Affiliations
Meta-Analysis

Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID-19

Haoran Zhang et al. Immun Inflamm Dis. 2024 Mar.

Abstract

Background: Patients with coronavirus disease-2019 (COVID-19) are characterized by hyperinflammation. Calprotectin (S100A8/S100A9) is a calcium- and zinc-binding protein mainly secreted by neutrophilic granulocytes or macrophages and has been suggested to be correlated with the severity and prognosis of COVID-19.

Aim: To thoroughly evaluate the diagnostic and prognostic utility of calprotectin in patients with COVID-19 by analyzing relevant studies.

Methods: PubMed, Web of Science, and Cochrane Library were comprehensively searched from inception to August 1, 2023 to retrieve studies about the application of calprotectin in COVID-19. Useful data such as the level of calprotectin in different groups and the diagnostic efficacy of this biomarker for severe COVID-19 were extracted and aggregated by using Stata 16.0 software.

Results: Fifteen studies were brought into this meta-analysis. First, the pooled standardized mean differences (SMDs) were used to estimate the differences in the levels of circulating calprotectin between patients with severe and non-severe COVID-19. The results showed an overall estimate of 1.84 (95% confidence interval [CI]: 1.09-2.60). Diagnostic information was extracted from 11 studies, and the pooled sensitivity and specificity of calprotectin for diagnosing severe COVID-19 were 0.75 (95% CI: 0.64-0.84) and 0.88 (95% CI: 0.79-0.94), respectively. The AUC was 0.89 and the pooled DOR was 18.44 (95% CI: 9.07-37.51). Furthermore, there was a strong correlation between elevated levels of circulating calprotectin and a higher risk of mortality outcomes in COVID-19 patients (odds ratio: 8.60, 95% CI: 2.17-34.12; p < 0.1).

Conclusion: This meta-analysis showed that calprotectin was elevated in patients with severe COVID-19, and this atypical inflammatory cytokine might serve as a useful biomarker to distinguish the severity of COVID-19 and predict the prognosis.

Keywords: COVID-19; biomarker; calprotectin; meta-analysis; systematic review.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA 2009 flow diagram. A total of 647 records were retrieved, after inclusion and exclusion criteria, the final 15 studies were included.
Figure 2
Figure 2
Review authors' judgements about each risk of bias item for included studies. (A) Risk of bias summary; (B) risk of bias graph presented as percentages.
Figure 3
Figure 3
Forest plot of calprotectin levels.
Figure 4
Figure 4
Forest plots of sensitivity and specificity of calprotectin diagnosis value for COVID‐19 severity.
Figure 5
Figure 5
Forest plot for the combined diagnostic odds ratio of calprotectin.
Figure 6
Figure 6
Summary receiver operating characteristic curve of COVID‐19 severity detected by calprotectin.
Figure 7
Figure 7
Forest plot for the odds ratio of mortality.
See this image and copyright information in PMC

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