Children, adolescents with COVID-19 experience wide range of neurologic involvement

Many children and adolescents with COVID-19 or multisystem inflammatory syndrome experienced neurologic involvement, with largely transient symptoms, according to a case series of almost 1,700 patients published in JAMA Neurology.

“Although most children and adolescents are spared from severe COVID-19, there have been reports of life-threatening neurologic involvement in patients developing multisystem inflammatory syndrome in children (MIS-C), a relatively rare, hyperinflammatory, severe illness temporally associated with SARS-CoV-2 infection, presumably postinfectious,” the researchers wrote. “The frequency of neurologic involvement in children hospitalized with acute COVID-19 is unclear, with 150 of 4,190 patients reported across nine international case series.”

Kerri LaRovere, MD, a member of the neurocritical care program in the department of neurology at Boston Children’s Hospital and an assistant professor of neurology at Harvard Medical School, and colleagues aimed to determine the “range and severity” of neurologic involvement associated with COVID-19 in children and adolescents. The researchers conducted active surveillance at 61 hospitals in 31 states in the Overcoming COVID-19 network to identify children and adolescents aged younger than 21 years hospitalized due to SARS-CoV-2-related illness between March 15, 2020, and December 15, 2020.

The case series also included patients who met the criteria for MIS-C. Patients with neurologic involvement displayed acute neurologic signs, symptoms or diseases at the time of presentation or during the hospitalization. Outcomes included the type and severity of neurologic involvement, lab and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge, according to the study results.

Among 1,695 patients (54% boys and men; median age, 9.1 years [interquartile range, 2.4-15.3 years]), only 22% (n = 365) from 52 sites had documented neurologic involvement. LaRovere and colleagues found that patients with neurologic involvement were more likely to have underlying neurologic disorders (81/365; 22%) compared with patients without neurologic involvement (113/1,330; 8%). However, a similar number were previously healthy (195 [53%] vs. 723 [54%]) and met the criteria for MIS-C (126 [35%] vs. 490 [37%]).

Most patients who experienced neurologic symptoms had transient symptoms and survived (n = 322; 88%). The researchers observed a “broad” range of neurologic symptoms related to COVID-19 that varied by age; these symptoms included seizures/status epilepticus in younger patients and reports of anosmia and/or ageusia, headache and fatigue/weakness in older patients. Among those who developed life-threatening conditions “clinically adjudicated to be associated with COVID-19” (n = 43; 12%), symptoms included severe encephalopathy (n = 15, including 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4) and acute fulminant cerebral edema (n = 4).

The researchers found that, compared with those without life-threatening conditions (n = 322), patients with life-threatening neurologic conditions experienced higher neutrophil-to-lymphocyte ratios (median, 12.2 vs. 4.4) and higher reported frequency of D-dimer greater than 3 g/mL fibrinogen equivalent units (21 [49%] vs. 72 [22%]).

Among 43 patients who developed life-threatening neurologic involvement related to COVID-19, 17 survivors (40%) displayed new neurologic deficits at hospital discharge and 11 patients (26%) died. For survivors experiencing new neurologic deficits, most (94%; n = 16) were previously healthy, none had prior neurologic disorders, seven (41%) met the criteria for MIS-C and 14 (82%) required rehabilitative services after discharge.

LaRovere and colleagues acknowledged several limitations of the study, including the fact that cases of neurological involvement associated with COVID-19 were identified only at reporting hospitals and therefore “may not accurately reflect the true range and severity of COVID-19 neurologic involvement.” They also noted that certain neurologic symptoms, such as anosmia or ageusia, could be underreported in very young patients and that the study involved a case series, not a retrospective cohort study.

“Future immunologic studies of cell-mediated and cytokine immune responses in young individuals may provide insight into the pathogenesis of neurologic disease in COVID-19 and MIS-C. Patients with less severe neurologic involvement could have future sequelae,” the researchers wrote. “Long-term follow-up of pediatric patients with COVID-19–related neurologic involvement is needed to evaluate effects on cognition and development.”