2853. Innate Immune Response in Serum and Cerebrospinal Fluid of Neonates and Infants Infected with Parechovirus-A3 and Enteroviruses

Abstract Background Parechovirus-A3 (PeV-A3) and enteroviruses (EVs) are the most common viral causes of neonatal and infantile sepsis. We previously reported that the clinical manifestations of PeV-A3 infection—e.g., high body temperature, tachycardia, and poor peripheral circulation, but not cerebrospinal fluid (CSF) pleocytosis—tend be more severe than those of EV infection. We tested the hypothesis that innate immune responses to PeV-A3 and EVs are distinct. Methods Using serum and CSF samples, we investigated immune responses of febrile neonates and infants <4 months in Niigata, Japan, from 2015 through 2018. PeV-A and EV infections were diagnosed with real-time PCR. PeV-A3 infection was diagnosed by sequence analysis of the VP1 region. The control was clinically well patients without serum and CSF findings suggestive of bacterial or viral etiology. The Milliplex MAP human cytokine/chemokine magnetic bead panel (Merck Millipore, Germany) was used to analyze 22 cytokines/chemokines related to innate immunity in serum and CSF. Results We evaluated 14 PeV-A3-infected and 15 EV-infected patients and 8 controls. Serum levels of proinflammatory cytokines/chemokines (fractalkine, interferon-α2, interleukin [IL]-1 receptor α, IL-6, IL-8, and IL-15) were significantly higher in PeV-A3-infected patients than in EV-infected patients (P < 0.005). Serum cytokine/chemokine profiles of EV-infected patients did not differ from those of controls. However, while most pro- and anti-inflammatory cytokines/chemokines in CSF were elevated in EV-infected patients, levels were low or undetectable in PeV-A3-infected patients and controls (P < 0.005). Conclusion PeV-A3-infected patients had high serum levels of proinflammatory cytokines/chemokines, which may explain why clinical manifestations were more severe in this patient group than in EV-infected patients. Conversely, the limited or nonexistent innate immune response in CSF from PeV-A3-infected patients might explain the absence of CSF pleocytosis. These findings improve our understanding of the differing pathophysiological characteristics of PeV-A3 and EV infection in neonates and young infants. Disclosures All Authors: No reported Disclosures.