The coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, becomes clinically manifest in a broad range from mild symptoms to life-threatening multi-organ failure (MOF). We have read with interest the recent letter by García de Guadiana Romualdo and colleagues1 and the review by Skevaki and colleagues2 examining the significance of biomarkers for risk assessment and prognosis of COVID-19.

A severe course of disease is characterized by a dysregulated immune response, suspected to be initiated by dysregulation of innate immune cells of the granulomonocytic lineage. 3 The proinflammatory mediator calprotectin (S100A8/A9, MRP 8/14) is reported to be an early signal, mediating the cytokine storm associated with an increased severity of COVID-19. 1, 3, 4 The expression of calprotectin is predominantly restricted to the intracellular compartment of neutrophil granulocytes, where it presents about half of the total cytosolic protein content. In contrast to routinely used inflammatory biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT), it is released into the bloodstream without need for de novo protein biosynthesis. Thereby, circulating calprotectin possibly has a decisive kinetic advantage in that it might be one of the first responses of an organism to an inflammatory disease.