Absent pleocytosis in infant viral central nervous system infections reflects lymphocyte depletion and cytokine activation

Enterovirus and parechovirus infections are common causes of fever in young infants and frequently prompt evaluation for meningitis. A notable feature of these infections is that many infants have detectable viral genetic material in the cerebrospinal fluid but no increase in white blood cells. This absence of pleocytosis has been attributed to early presentation, immature or suppressed immune responses, or incidental virus detection during systemic infection rather than true central nervous system (CNS) infection or meningitis. Here, we clarify the clinical and biological significance of absent pleocytosis in infant viral CNS infections using plasma proteomic profiling and detailed clinical data from a prospective multicentre cohort of febrile infants. We show that infants without pleocytosis display lymphopenia and marked activation of inflammatory and apoptotic pathways in the plasma, implicating lymphocyte depletion in impaired cerebrospinal fluid leucocyte recruitment and supporting true neurological infection.