Neurologic manifestations in an infant with COVID-19

Case

A 6-week-old term male infant presented for evaluation after 1 day of cough, fever, and brief episodes of sustained upward gaze associated with bilateral leg stiffening. The initial episode occurred after a diaper change. There was no shaking, breathing change, or pallor during this episode. There was no association with feeding. The infant had 2 siblings with cough and fever at the time of presentation, both diagnosed with streptococcal pharyngitis. On arrival to the emergency department, vital signs were notable for fever of 38.4°C and mild hypertension (114/57). Examination was notable for a mottled appearance and bilateral overlapping of the fourth and fifth toes. The anterior fontanel was soft and nonbulging, and neurologic examination was unremarkable. However, the patient had a witnessed episode of sustained upward gaze associated with bilateral leg stiffening and decreased responsiveness lasting 10 seconds with subsequent return to baseline and no hypoxia or vital signs change.

The patient was born at 39 weeks via uncomplicated normal spontaneous vaginal delivery, weighing 3.91 kg. Family history was notable for simple febrile seizures in a developmentally normal sibling. There was no family history of epilepsy.

Laboratory data were notable for leukopenia of 5.07 ×10³ white blood cells (wbcs)/µL (normal 8.14–14.99 × 10³) with a normal differential and elevated procalcitonin of 0.21 ng/mL (normal <0.08 ng/mL). Electrolytes were normal. Respiratory pathogen PCR panel was positive for rhinovirus/enterovirus. SARS-CoV-2 Real-Time Reverse Transcriptase (rRT)-PCR was positive. A chest radiograph was not performed. A lumbar puncture had an unremarkable CSF profile with one red blood cell and 2 wbcs/µL, glucose of 50 mg/dL, serum glucose of 84 mg/dL, and protein of 40 mg/dL. Meningitis/encephalitis PCR panel was negative. CSF culture showed no cells nor organisms. Standard CSF testing does not detect COVID-19.

The patient was connected to long-term EEG monitoring which showed an excess of temporal sharp transients for age and intermittent vertex delta slowing with normal sleep-wake cycling. MRI of the brain with and without contrast to rule out a corresponding structural lesion was normal. Given the abnormal EEG findings and unexplained clinical events, further CSF, nasopharyngeal swab, serum, plasma, and anal swab testing were performed using high throughput sequencing and quantitative rRT-PCR after obtaining parental consent (see supplementary e-Methods, doi.org/10.5061/dryad.v41ns1rsc).

rRT-PCR nasopharyngeal swab testing was positive for SARS-CoV-2 RNA (∼2 × 10⁶ copies/mL). Anal swab testing showed low levels of viral RNA (∼200 copies/mL). SARS-CoV-2 RNA was not detected in CSF, serum, nor plasma. High throughput sequencing showed SARS-CoV-2 RNA and rhinovirus C sequences in nasopharyngeal and anal swab samples. Moraxella and Corynebacterium, common nasal flora, were detected in the nasopharyngeal swab (see supplementary e-Results, doi.org/10.5061/dryad.v41ns1rsc).

The patient was discharged home 1 day after admission without further fever or events on follow-up 1 week later.