Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity
Authors: Francoeur Conall , Alcamo Alicia M. , Robertson Courtney L. , Wainwright Mark S. , Roa Juan D. , Lovett Marlina E. , Stulce Casey , Yacoub Mais , Potera Renee M. , Zivick Elizabeth , Holloway Adrian , Nagpal Ashish , Wellnitz Kari , Even Katelyn M. , Brunow de Carvalho Werther , Rodriguez Isadora S. , Schwartz Stephanie P. , Walker Tracie C. , Campos-Miño Santiago , Dervan Leslie A. , Geneslaw Andrew S. , Sewell Taylor B. , Pryce Patrice , Silver Wendy G. , Lin Jieru E. , Vargas Wendy S. , Topjian Alexis , McGuire Jennifer L. , Domínguez Rojas Jesus Angel , Tasayco-Muñoz Jaime , Hong Sue J. , Muller William J. , Doerfler Matthew , Williams Cydni N. , Drury Kurt , Bhagat Dhristie , Nelson Aaron , Price Dana , Dapul Heda , Santos Laura , Kahoud Robert , Appavu Brian , Guilliams Kristin P. , Agner Shannon C. , Walson Karen H. , Rasmussen Lindsey , Pal Ria , Janas Anna , Ferrazzano Peter , Farias-Moeller Raquel , Snooks Kellie C. , Chang Chung-Chou H. , Iolster Tomás , Erklauer Jennifer C. , Jorro Baron Facundo , Wassmer Evangeline , Yoong Michael , Jardine Michelle , Mohammad Zoha , Deep Akash , Kendirli Tanil , Lidsky Karen , Dallefeld Samantha , Flockton Helen , Agrawal Shruti , Siruguppa Krishna Sumanth , Waak Michaela , Gutiérrez-Mata Alfonso , Butt Warwick , Bogantes-Ledezma Sixto , Sevilla-Acosta Fabricio , Umaña-Calderón Andres , Ulate-Campos Adriana , Yock-Corrales Adriana , Talisa Victor Brodzik , Kanthimathinathan Hari Krishnan , Schober Michelle E. , Fink Ericka L. ,   Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) Investigators
Published: June 2024

Importance

Neurological manifestations during acute SARS-CoV-2–related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity.

Objective

To assess the association of severe neurological manifestations during a SARS-CoV-2–related hospital admission with new neurocognitive or functional morbidities at discharge.

Design, Setting, and Participants

This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021.

Exposure

Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke.

Main Outcomes and Measures

The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2–related condition.

Results

Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P &amp;lt; .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge.

Conclusions and Relevance

The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.