tetano
Editor, Senior Moderator
JAMA Neurol
. 2021 Mar 5.
doi: 10.1001/jamaneurol.2021.0504. Online ahead of print.
Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome
Kerri L LaRovere[SUP] 1 [/SUP], Becky J Riggs[SUP] 2 [/SUP], Tina Y Poussaint[SUP] 3 [/SUP], Cameron C Young[SUP] 4 [/SUP], Margaret M Newhams[SUP] 4 [/SUP], Mia Maamari[SUP] 5 [/SUP], Tracie C Walker[SUP] 6 [/SUP], Aalok R Singh[SUP] 7 [/SUP], Heda Dapul[SUP] 8 [/SUP], Charlotte V Hobbs[SUP] 9 [/SUP], Gwenn E McLaughlin[SUP] 10 [/SUP], Mary Beth F Son[SUP] 11 [/SUP], Aline B Maddux[SUP] 12 [/SUP], Katharine N Clouser[SUP] 13 [/SUP], Courtney M Rowan[SUP] 14 [/SUP], John K McGuire[SUP] 15 [/SUP], Julie C Fitzgerald[SUP] 16 [/SUP], Shira J Gertz[SUP] 17 [/SUP], Steven L Shein[SUP] 18 [/SUP], Alvaro Coronado Munoz[SUP] 19 [/SUP], Neal J Thomas[SUP] 20 [/SUP], Katherine Irby[SUP] 21 [/SUP], Emily R Levy[SUP] 22 [/SUP], Mary A Staat[SUP] 23 [/SUP], Mark W Tenforde[SUP] 24 25 [/SUP], Leora R Feldstein[SUP] 24 25 [/SUP], Natasha B Halasa[SUP] 26 [/SUP], John S Giuliano Jr[SUP] 27 [/SUP], Mark W Hall[SUP] 28 [/SUP], Michele Kong[SUP] 29 [/SUP], Christopher L Carroll[SUP] 30 [/SUP], Jennifer E Schuster[SUP] 31 [/SUP], Sule Doymaz[SUP] 32 [/SUP], Laura L Loftis[SUP] 33 [/SUP], Keiko M Tarquinio[SUP] 34 [/SUP], Christopher J Babbitt[SUP] 35 [/SUP], Ryan A Nofziger[SUP] 36 [/SUP], Lawrence C Kleinman[SUP] 37 [/SUP], Michael A Keenaghan[SUP] 38 [/SUP], Natalie Z Cvijanovich[SUP] 39 [/SUP], Philip C Spinella[SUP] 40 [/SUP], Janet R Hume[SUP] 41 [/SUP], Kari Wellnitz[SUP] 42 [/SUP], Elizabeth H Mack[SUP] 43 [/SUP], Kelly N Michelson[SUP] 44 [/SUP], Heidi R Flori[SUP] 45 [/SUP], Manish M Patel[SUP] 24 25 [/SUP], Adrienne G Randolph[SUP] 4 46 [/SUP], Overcoming COVID-19 Investigators
Collaborators, Affiliations
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-Barr? 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.
. 2021 Mar 5.
doi: 10.1001/jamaneurol.2021.0504. Online ahead of print.
Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome
Kerri L LaRovere[SUP] 1 [/SUP], Becky J Riggs[SUP] 2 [/SUP], Tina Y Poussaint[SUP] 3 [/SUP], Cameron C Young[SUP] 4 [/SUP], Margaret M Newhams[SUP] 4 [/SUP], Mia Maamari[SUP] 5 [/SUP], Tracie C Walker[SUP] 6 [/SUP], Aalok R Singh[SUP] 7 [/SUP], Heda Dapul[SUP] 8 [/SUP], Charlotte V Hobbs[SUP] 9 [/SUP], Gwenn E McLaughlin[SUP] 10 [/SUP], Mary Beth F Son[SUP] 11 [/SUP], Aline B Maddux[SUP] 12 [/SUP], Katharine N Clouser[SUP] 13 [/SUP], Courtney M Rowan[SUP] 14 [/SUP], John K McGuire[SUP] 15 [/SUP], Julie C Fitzgerald[SUP] 16 [/SUP], Shira J Gertz[SUP] 17 [/SUP], Steven L Shein[SUP] 18 [/SUP], Alvaro Coronado Munoz[SUP] 19 [/SUP], Neal J Thomas[SUP] 20 [/SUP], Katherine Irby[SUP] 21 [/SUP], Emily R Levy[SUP] 22 [/SUP], Mary A Staat[SUP] 23 [/SUP], Mark W Tenforde[SUP] 24 25 [/SUP], Leora R Feldstein[SUP] 24 25 [/SUP], Natasha B Halasa[SUP] 26 [/SUP], John S Giuliano Jr[SUP] 27 [/SUP], Mark W Hall[SUP] 28 [/SUP], Michele Kong[SUP] 29 [/SUP], Christopher L Carroll[SUP] 30 [/SUP], Jennifer E Schuster[SUP] 31 [/SUP], Sule Doymaz[SUP] 32 [/SUP], Laura L Loftis[SUP] 33 [/SUP], Keiko M Tarquinio[SUP] 34 [/SUP], Christopher J Babbitt[SUP] 35 [/SUP], Ryan A Nofziger[SUP] 36 [/SUP], Lawrence C Kleinman[SUP] 37 [/SUP], Michael A Keenaghan[SUP] 38 [/SUP], Natalie Z Cvijanovich[SUP] 39 [/SUP], Philip C Spinella[SUP] 40 [/SUP], Janet R Hume[SUP] 41 [/SUP], Kari Wellnitz[SUP] 42 [/SUP], Elizabeth H Mack[SUP] 43 [/SUP], Kelly N Michelson[SUP] 44 [/SUP], Heidi R Flori[SUP] 45 [/SUP], Manish M Patel[SUP] 24 25 [/SUP], Adrienne G Randolph[SUP] 4 46 [/SUP], Overcoming COVID-19 Investigators
Collaborators, Affiliations
- PMID: 33666649
- DOI: 10.1001/jamaneurol.2021.0504
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-Barr? 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.