Neutrophils are critical immune cells in severe coronavirus disease 2019 (COVID-19). S100
calcium-binding protein A12 (S100A12) is highly expressed in neutrophils during acute inflammation.
The aim of this study was to evaluate serum S100A12 levels as a diagnostic and prognostic tool in
COVID-19. Serum samples of patients with moderate and severe COVID-19 were collected during
2020 to 2024. Enzyme-linked immunosorbent assay was used to measure serum S100A12 levels in
63 patients with moderate COVID-19, 60 patients with severe disease and 33 healthy controls. Serum
S100A12 levels were elevated in moderate COVID-19 compared to controls and were even higher
in severe cases. In moderate disease, serum S100A12 levels positively correlated with immune cell
counts. While C-reactive protein and procalcitonin are established inflammation markers, they did
not correlate with serum S100A12 levels in either patient cohort. Patients with severe COVID-19 and
vancomycin-resistant enterococcus (VRE) infection had increased S100A12 levels. Elevated S100A12
levels were also observed in patients with herpes simplex reactivation. Fungal superinfections did
not alter S100A12 levels. These data show that serum S100A12 increases in moderate and severe
COVID-19 and is further elevated by VRE bloodstream infection and herpes simplex reactivation.
Therefore, S100A12 may serve as a novel biomarker for severe COVID-19 and an early diagnostic
indicator for bacterial and viral infections.