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22% of children with COVID or MIS-C had neurologic conditions — US hospital study

Among US children and teens hospitalised with COVID-19 or its related multisystem inflammatory syndrome in children (MIS-C), 22% had neurologic conditions, most of them transient but 12% of them life-threatening or fatal, according to a study.

A team led by researchers at Boston Children's Hospital studied 1,695 patients with COVID-19 younger than 21 years admitted to 61 hospitals, 616 (36%) of whom also had MIS-C, from 15 March to 15 December, 2020. Neurologic involvement was identified in 365 (22%) of patients from 52 hospitals.

Patients with neurologic symptoms were more likely than their peers to have underlying neurologic conditions (81 of 365 [22%] vs 113 of 1,330 [8%]). But 53% had been healthy, compared with 54% of those without neurologic symptoms. Also, patients with neurologic symptoms had similar rates of MIS-C as those who didn't have neurologic symptoms (126 [35%] vs 490 [37%]).

Neurologic symptoms were transient and non–life-threatening among 322 of 365 (88%) children, while 43 (12%) developed life-threatening coronavirus-related conditions, including severe encephalopathy (brain damage or dysfunction) (15 patients, 5 with splenial lesions [on the corpus callosum in the brain]), stroke (12), central nervous system infection/demyelination (damage to the brain's protective covering) (8), Guillain-Barre syndrome/variants (4), and acute fulminant cerebral swelling (4).

Among the 43 children with life-threatening neurologic involvement, 17 survivors (40%) had new neurologic disabilities at hospital release, and 11 patients (26%) died.

Patients with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (indicating inflammation) (median, 12.2 vs 4.4) and D-dimer concentrations (indicating blood clots) (49% vs 22%). Median patient age was 9.1 years, and 54% were male. Roughly one in four children with neurologic involvement had altered awareness or confusion.

The authors said that the long-term effects on neurodevelopmental outcomes among these children are unknown. "Patients with less severe neurologic involvement could have future sequelae," they wrote. "Long-term follow-up of paediatric patients with COVID-19–related neurologic involvement is needed to evaluate effects on cognition and development."

 

Study details
Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome

Kerri L LaRovere; Becky J Riggs; Tina Y Poussaint; Cameron C Young; Margaret M Newhams; Mia Maamari; Tracie C Walker; Aalok R Singh; Heda Dapul; Charlotte V Hobbs; Gwenn E McLaughlin; Mary Beth F Son; Aline B Maddux; Katharine N Clouser; Courtney M Rowan; John K McGuire; Julie C Fitzgerald; Shira J Gertz; Steven L Shein; Alvaro Coronado Munoz; Neal J Thomas; Katherine Irby; Emily R Levy; Mary A Staat; Mark W Tenforde; Leora R Feldstein; Natasha B Halasa; John S Giuliano Jr; Mark W Hall; Michele Kong; Christopher L Carrol; Jennifer E Schuster; Sule Doymaz, ; Laura L Loftis; Keiko M Tarquinio; Christopher J Babbitt; Ryan A Nofziger; Lawrence C Kleinman; Michael A Keenaghan; Natalie Z Cvijanovich; Philip C Spinella; Janet R Hume; Kari Wellnitz; Elizabeth H Mack; Kelly N. Michelson; Heidi R Flori; Manish M Patel; Adrienne G Randolph; for the Overcoming COVID-19 Investigators

Published in JAMA Neurology on 5 March 2021

Abstract
Importance
Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear.
Objective
To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19.
Setting, Design, and Participants
Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features.
Exposures
Severe acute respiratory syndrome coronavirus 2.
Main Outcomes and Measures
Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge.
Results
Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 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). Compared with those without life-threatening conditions (n = 322), those 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 (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19–related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died.
Conclusions and Relevance
In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.

 

[link url="https://jamanetwork.com/journals/jamaneurology/fullarticle/2777392"]JAMA Neurology study (Open access)[/link]

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