Habuka R, Aizawa Y, Izumita R, et al. - The most common viruses causing sepsis and meningoencephalitis in neonates and young infants are parechovirus-A3 (PeV-A3) and enteroviruses (EV). Clinical manifestations of PeV-A3 infection, vs those of EV infection, are more severe, and its characteristic findings are no pleocytosis with a positive PCR result for PeV-A3 in cerebrospinal fluid (CSF). Researchers here examined if innate immune responses to PeV-A3 and EV are distinct in serum and CSF. Serum and CSF from PeV-A3- or EV-infected patients younger than 4 months in Niigata, Japan were evaluated for 22 cytokines/chemokines from 2015 through 2018. They evaluated 192 febrile patients; of these, 16 were PeV-A3-infected, 15 were EV-infected, and 8 were non–PeV-A/EV patients. They identified higher serum pro-/anti-inflammatory cytokine/chemokine levels in PeV-A3-infected patients vs EV-infected patients. While EV-infected patients had elevation of most cytokine/chemokine in CSF, PeV-A3-infected and non–PeV-A/EV patients had low or undetectable levels. Findings suggest that the different clinical manifestations of PeV-A3-infected and EV-infected neonates and young infants may be explained with distinct cytokine/chemokine patterns in serum and CSF.