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

description: 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 < .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.