Most are transient, but some develop into life-threatening disorders
Neurologic symptoms occurred frequently in children and adolescents hospitalized with COVID-19, a large case series of pediatric patients in the U.S. showed.
Of 1,695 people 21 or younger hospitalized for acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C), more than one in five (22%) had neurologic involvement, reported Adrienne Randolph, MD, of Boston Children’s Hospital, and co-authors.
Most symptoms were transient, but 12% of children with neurologic involvement developed life-threatening neurologic disorders, Randolph and colleagues wrote in JAMA Neurology.
“Our findings highlight that neurologic involvement is common in children and adolescents hospitalized for COVID-19,” said co-author Kerri LaRovere, MD, of Boston Children’s Hospital. “Children with underlying neurologic disorders may be at increased risk of neurologic complications, but we also found that many children were previously healthy and did not have prior neurologic conditions,” she told.
Most children and adolescents do not develop severe COVID-19. Reports of life-threatening neurologic involvement in patients developing MIS-C, a rare inflammatory illness temporally associated with SARS-CoV-2 infection, have emerged since the pandemic started, with cases rising when infection rates surged.
In their study, Randolph and co-researchers analyzed data from the Overcoming COVID-19 registry of pediatric patients from 61 hospitals in 31 states from March 15 to December 15, 2020. Participants were hospitalized for acute illness and had a positive SARS-CoV-2 test and symptoms associated with acute COVID-19, or met CDC criteria for MIS-C. Patients with asymptomatic SARS-CoV-2 infection or who had hospitalization or death not related to COVID-19 were excluded.
Just more than half (54%) of participants were male, and median age was 9. While patients with neurologic involvement were more likely to have underlying neurologic disorders (22%) than not (8%), similar numbers were previously healthy (53% vs 54%) and met criteria for MIS-C (35% vs 37%).
Neurologic symptoms associated with COVID-19 varied by age, from seizures or status epilepticus in younger patients to anosmia, ageusia, headache, fatigue, and weakness in older patients. Overall, about one in four pediatric patients with neurologic involvement had altered awareness or confusion.
Most (88%) pediatric patients who had neurologic involvement had transient symptoms and survived. Forty-three patients (12%) developed life-threatening conditions associated with COVID-19, including:
- Severe encephalopathy (15 patients, including five with splenial lesions)
- Stroke (12 patients)
- Central nervous system infection or demyelination (eight patients)
- Guillain-Barré syndrome or variants (four patients)
- Acute fulminant cerebral edema (four patients)
Patients with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (49% vs 22%) compared with those whose neurologic involvement was not life-threatening.
Of patients with life-threatening neurologic conditions, 11 patients (26%) died and 17 (40%) survived with new neurologic sequelae. Children who died included four patients with stroke and four who developed severe encephalopathy. Of survivors with new deficits, 16 (94%) were previously healthy, none had prior neurologic disorders, and 7 (41%) met MIS-C criteria.
“Hispanic or Latino and non-Hispanic Black children and adolescents represented a high proportion of the cases with severe neurologic involvement,” noted co-author Tina Young Poussaint, MD, also of Boston Children’s Hospital.
“There should be a high index of suspicion for COVID-19-related neurologic involvement for any young individual presenting with a broad range of neurologic symptoms or severe neurologic conditions following exposure to COVID-19 or a positive SARS-CoV-2 test,” Poussaint told.
“Minimizing exposure by following the CDC guidelines, even for healthy children, is important because the full extent of neurologic involvement and long-term effects on cognition and development are unknown,” she added.
The study had several limitations, the researchers noted. Cases came only from reporting hospitals and do not reflect the true range and severity of COVID-19 neurologic involvement. In patients with underlying neurologic diseases, some presentations may be an exacerbation of their condition. Not all patients had imaging, and some symptoms, like anosmia or ageusia, may be underreported in very young patients.