Neurologic Findings and Cerebrospinal Fluid Biomarkers in Neonates With SARS-CoV-2 Infection: A Multicenter National...

Neurologic manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in neonates are poorly characterized, and central nervous system (CNS) involvement may be difficult to recognize due to nonspecific symptoms. The role of cerebrospinal fluid (CSF) biomarkers in detecting CNS inflammation or neuronal injury in this population remains unclear. We aimed to characterize neurologic manifestations and evaluate CSF findings in affected neonates.

In this prospective multicenter national cohort study conducted in Spain (October 2020-July 2022), neonates 0-28 days old with confirmed SARS-CoV-2 infection and fever and/or neurologic symptoms were included. Neurologic evaluation, CSF analysis, and neuroimaging were performed when clinically indicated. CSF biomarkers (β2-microglobulin [B2M] and neuron-specific enolase [NSE]) were analyzed and compared with age-matched controls.

Sixty-one neonates were included (median age 16 days). Neurologic symptoms were observed in 27 (44.3%), mainly irritability, lethargy, tone alteration or apnea, and were transient in all cases. Lumbar puncture was performed in 20 neonates; no microbiologically confirmed meningitis or CSF SARS-CoV-2 detection was identified. CSF B2M levels were significantly higher in infected neonates compared with age-matched controls, whereas NSE levels were similar. No severe neurologic complications or deaths occurred.

Neonatal SARS-CoV-2 infection was associated with mild and transient neurologic symptoms without evidence of meningoencephalitis. Elevated CSF B2M with normal NSE suggests subclinical CNS immune activation without neuronal injury.