Serum Calprotectin in Hospitalized Patients with COVID-19 in Relation to High-Dimensional Serum Proteomic Patterns

Calprotectin in blood has been identified as a potential biomarker for severe COVID-19 and sepsis. As a knowledge gap remains regarding the biological role of calprotectin, we aimed to investigate the association between serum calprotectin and the circulating proteome in patients with COVID-19 as a model for viral sepsis. In this observational study, serum samples were collected from 160 hospitalized adult patients with COVID-19. The samples were analyzed for calprotectin using a routine turbidimetric assay and for proteomics using the Olink Explore 1536 platform. Patients were classified as having severe or moderate COVID-19 according to oxygen supply on the day of blood sampling. The median calprotectin level was significantly higher in patients with severe compared to moderate COVID-19. In relation to proteomics, calprotectin levels were associated with a neutrophil-centered inflammatory proteomic signature, characterized by upregulation of cytokine and danger-signaling pathways. S100A12 showed the strongest correlation to calprotectin. In conclusion, calprotectin is associated with disease severity in COVID-19, and high levels reflect a neutrophil-driven inflammatory proteomic profile, particularly involving S100A12. These findings support calprotectin as a biomarker of neutrophil-mediated hyperinflammation in viral sepsis.