Neurological Manifestations of SARS-CoV-2 in Hospitalized Children: A Multi-National Cohort Study

Background: Knowledge about neurological manifestations of SARS-CoV-2 in children is limited. We describe neurological manifestations in an international cohort of hospitalized pediatric patients. Methods: This is a multi-national observational study involving tertiary healthcare institutions in Canada, Costa Rica and Iran. We included patients 1 day-18 years admitted for any medical reason February 1, 2020-January 31, 2021 with laboratory evidence of SARS-CoV-2 infection by RT-PCR or serological testing. Descriptive analyses and logistic regression were performed where appropriate using JASP version 0⋅13. Findings: 298 hospitalized children with confirmed SARS-CoV-2 infection (median age 3⋅9 years [IQR 0⋅6-10⋅1]) from Canada (n=152), Costa Rica (n=115) and Iran (n=31) were included. Fifty-one (17%) had neurological manifestations, of which headache (73%), seizures (23%) and altered mental status (6%) were most frequently seen. Children with neurological symptoms had equivalent rates of comorbidities overall but were more likely to have underlying chronic neurological conditions.  Additionally, those with neurological symptoms were more likely to be admitted to the ICU (15/51 [29%] vs. 32/247 [13%]; p =0⋅0033) and had longer length of hospital stay (6 days [IQR 3-8] vs. 4 days [IQR 2-7]; p =0⋅0060). Abnormalities were found in all children with neurological manifestations who received neuroimaging (n=6). Neurological manifestations were seen in 19% of the Iranian cohort, 23% of the Costa Rican cohort, and 12% of the Canadian cohort. Country of residence Costa Rica (adjusted OR: 2⋅520, 95% CI: 1⋅325-4⋅791, p =0⋅005), ICU admission (adjusted OR: 2⋅678, 95% CI: 1⋅307-5⋅486, p =0⋅007) and number of acute SARS-CoV-2 infection symptoms (adjusted OR: 1⋅355, 95% CI: 1⋅232-1⋅491, p <0⋅0001) were independently associated with neurological manifestations using multivariate analysis. Interpretation: We show that children with underlying comorbidities, especially underlying neurological diagnoses, are more likely to develop neurological complications of SARS CoV-2, and that sociodemographic factors, such as country of residence associate with varying rates of neurological manifestations. Future studies should focus on long-term outcomes in these children. Funding Statement: There was no funding source for this study. Declaration of Interests: Unrelated to this work, E.A. Yeh has received research funding from NMSS, CMSC, CIHR, NIH, OIRM, SCN, CBMH Chase an Idea, SickKids Foundation, Rare Diseases Foundation, MS Scientific Foundation (Canada), McLaughlin Centre, Mario Battaglia Foundation. Investigator initiated research funding from Biogen. Scientific advisory: Biogen, Hoffman-LaRoche, Vielabio. Speaker honoraria: Saudi Epilepsy Society, NYU, MS-ATL; ACRS, PRIME. J. Papenburg holds a “Chercheur-boursier clinicien” career award from the Fonds de recherche du Quebec – Sante (FRQS) and reports grants from MedImmune, grants from Sanofi Pasteur, personal fees from Seegene, grants and personal fees from AbbVie, outside the submitted work. All other authors declare no conflict of interest. Ethics Approval Statement: All clinical and laboratory investigations were performed according to institutional protocols. Informed consent and ethics approval were obtained following requirements of the research ethics board of each participating institution.