Hyperferritinemia in neonatal and infantile human parechovirus-3 infection in comparison with other infectious diseases

Human parechovirus-3 (HPeV-3) has been associated with severe clinical manifestations in neonates and infants in the form of sepsis or hemophagocytic lymphohistiocytosis (HLH)-like illness. To clarify the clinical features of HPeV-3 infection, we compared clinical signs and laboratory findings among enteroviruses (EVs), HPeV-3, and other infections. Participants were 26 febrile infants in whom EVs (n = 20) or HPeV-3 (n = 6) were isolated from throat swab or fecal specimens. Clinical and laboratory data were compared among EVs, HPeV-3, respiratory syncytial virus (RSV) infection (n = 15), and bacterial meningitis (n = 8) groups. Apnea was frequently seen in the HPeV-3 group although there were no significant differences in other clinical symptoms. Leukocyte count was significantly lower in the HPeV-3 group than in the EV and RSV group. Platelet count was significantly lower in the HPeV-3 group than in the RSV group. Serum ferritin levels in the HPeV-3 group (mean, 2437 ng/ml) and EV group (mean, 552 ng/ml) were significantly higher than in the RSV group (mean 237 ng/ml; P = 0.008 and P = 0.002, respectively). The frequency of patients with clearly high ferritin levels ≥1000 ng/ml was comparatively higher in the HPeV-3 group (4/6) than the EV group (3/20) (P = 0.03). In the HPeV-3 group, ferritin levels were high on Days 4-5. Elevated ferritin levels, decreased leukocyte and platelet counts could offer diagnostic clues to HPeV-3 infection in infant. These laboratory findings might be associated with aberrant immune response to HPeV-3, which could contribute to the development of sepsis or HLH-like illness in neonates.