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

27 Pages Posted: 22 Apr 2021

See all articles by Carmen Yea

Carmen Yea

University of Toronto - Program for Neuroscience and Mental Health

Michelle Barton

University of Western Ontario - Department of Pediatrics

Ari Bitnun

University of Toronto - Division of Infectious Diseases

Shaun K. Morris

University of Toronto - The Hospital for Sick Children - SickKids

Tala El Tal

University of Toronto - Division of Rheumatology

Rolando Ulloa-Gutierrez

Caja Costarricense de Seguro Social (CCSS) - Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera”

Helena Brenes-Chacon

Caja Costarricense de Seguro Social (CCSS) - Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera”

Adriana Yock-Corrales

Caja Costarricense de Seguro Social (CCSS) - Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera”

Gabriela Ivankovich-Escoto

Caja Costarricense de Seguro Social (CCSS) - Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera”

Alejandra Soriano-Fallas

Caja Costarricense de Seguro Social (CCSS) - Pediatric Infectious Diseases Division

Marcela Hernandez de Mezerville

Caja Costarricense de Seguro Social (CCSS) - Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera”

Ronald M. Laxer

University of Toronto - Division of Rheumatology

Peter Gill

University of Toronto - Department of Pediatrics

Alireza Nateghian

Iran University of Medical Sciences

Behzad Haghighi Aski

Iran University of Medical Sciences

Ali Anari Manafi

Iran University of Medical Sciences

Rachel Dwilow

University of Manitoba

Jared Bullard

University of Manitoba

Jesse Papenburg

McGill University - Montreal Children's Hospital

Marie-Astrid Lefebvre

McGill University - Montreal Children's Hospital

Suzette Cooke

University of Calgary

Tammie Dewan

University of Calgary

Lea Restivo

University of Calgary

Alison Lopez

University of British Columbia (UBC) - Department of Pediatrics

Manish Sadarangani

BC Children's Hospital Research Institute - Vaccine Evaluation Center

Ashley Roberts

University of British Columbia (UBC) - Department of Pediatrics

Jacqueline Wong

McMaster University - Department of Pediatrics

Nicole Le Saux

University of Ottawa

Jennifer Bowes

University of Ottawa

Rupeena Purewal

University of Saskatchewan

Janell Lautermilch

University of Saskatchewan

Cheryl Foo

Memorial University

Joan Robinson

University of Alberta - Stollery Children's Hospital

E. Ann Yeh

University of Toronto - Division of Neurology

More...

Abstract

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 Québec – Santé (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.

Keywords: COVID-19, SARS-CoV-2, neurological manifestations, pediatrics

Suggested Citation

Yea, Carmen and Barton, Michelle and Bitnun, Ari and Morris, Shaun K. and El Tal, Tala and Ulloa-Gutierrez, Rolando and Brenes-Chacon, Helena and Yock-Corrales, Adriana and Ivankovich-Escoto, Gabriela and Soriano-Fallas, Alejandra and de Mezerville, Marcela Hernandez and Laxer, Ronald M. and Gill, Peter and Nateghian, Alireza and Aski, Behzad Haghighi and Manafi, Ali Anari and Dwilow, Rachel and Bullard, Jared and Papenburg, Jesse and Lefebvre, Marie-Astrid and Cooke, Suzette and Dewan, Tammie and Restivo, Lea and Lopez, Alison and Sadarangani, Manish and Roberts, Ashley and Wong, Jacqueline and Le Saux, Nicole and Bowes, Jennifer and Purewal, Rupeena and Lautermilch, Janell and Foo, Cheryl and Robinson, Joan and Yeh, E. Ann, Neurological Manifestations of SARS-CoV-2 in Hospitalized Children: A Multi-National Cohort Study. Available at SSRN: https://ssrn.com/abstract=3831858 or http://dx.doi.org/10.2139/ssrn.3831858

Carmen Yea

University of Toronto - Program for Neuroscience and Mental Health

555 University Ave
Toronto, Ontario
Canada

Michelle Barton

University of Western Ontario - Department of Pediatrics

London, Ontario
Canada

Ari Bitnun

University of Toronto - Division of Infectious Diseases

Toronto
Canada

Shaun K. Morris

University of Toronto - The Hospital for Sick Children - SickKids ( email )

Tala El Tal

University of Toronto - Division of Rheumatology ( email )

Toronto
Canada

Rolando Ulloa-Gutierrez

Caja Costarricense de Seguro Social (CCSS) - Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera” ( email )

San Jose
Costa Rica

Helena Brenes-Chacon

Caja Costarricense de Seguro Social (CCSS) - Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera” ( email )

San Jose
Costa Rica

Adriana Yock-Corrales

Caja Costarricense de Seguro Social (CCSS) - Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera” ( email )

San Jose
Costa Rica

Gabriela Ivankovich-Escoto

Caja Costarricense de Seguro Social (CCSS) - Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera” ( email )

San Jose
Costa Rica

Alejandra Soriano-Fallas

Caja Costarricense de Seguro Social (CCSS) - Pediatric Infectious Diseases Division

San Jose
Costa Rica

Marcela Hernandez De Mezerville

Caja Costarricense de Seguro Social (CCSS) - Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera” ( email )

San Jose
Costa Rica

Ronald M. Laxer

University of Toronto - Division of Rheumatology ( email )

Toronto, Ontario
Canada

Peter Gill

University of Toronto - Department of Pediatrics

Toronto, Ontario
Canada

Alireza Nateghian

Iran University of Medical Sciences

Hemmat Hwy
Tehran
Iran

Behzad Haghighi Aski

Iran University of Medical Sciences

Hemmat Hwy
Tehran
Iran

Ali Anari Manafi

Iran University of Medical Sciences

Hemmat Hwy
Tehran
Iran

Rachel Dwilow

University of Manitoba

501 F.A. Bldg
Winnipeg R3T 5V4, R3T 5V5
Canada

Jared Bullard

University of Manitoba

501 F.A. Bldg
Winnipeg R3T 5V4, R3T 5V5
Canada

Jesse Papenburg

McGill University - Montreal Children's Hospital ( email )

Decarie
Canada

Marie-Astrid Lefebvre

McGill University - Montreal Children's Hospital ( email )

Decarie
Canada

Suzette Cooke

University of Calgary

University Drive
Calgary, T2N 1N4
Canada

Tammie Dewan

University of Calgary

University Drive
Calgary, T2N 1N4
Canada

Lea Restivo

University of Calgary

University Drive
Calgary, T2N 1N4
Canada

Alison Lopez

University of British Columbia (UBC) - Department of Pediatrics ( email )

Vancouver, British Columbia
Canada

Manish Sadarangani

BC Children's Hospital Research Institute - Vaccine Evaluation Center ( email )

Canada

Ashley Roberts

University of British Columbia (UBC) - Department of Pediatrics

Vancouver, British Columbia
Canada

Jacqueline Wong

McMaster University - Department of Pediatrics

Canada

Nicole Le Saux

University of Ottawa

2292 Edwin Crescent
Ottawa, K2C 1H7
Canada

Jennifer Bowes

University of Ottawa

2292 Edwin Crescent
Ottawa, K2C 1H7
Canada

Rupeena Purewal

University of Saskatchewan

College of Education
Saskatoon, S7N 5A7
Canada

Janell Lautermilch

University of Saskatchewan

College of Education
Saskatoon, S7N 5A7
Canada

Cheryl Foo

Memorial University ( email )

230 Elizabeth Ave
St John's, NL A1B 3X9
Canada

Joan Robinson

University of Alberta - Stollery Children's Hospital

Edmonton, Alberta
Canada

E. Ann Yeh (Contact Author)

University of Toronto - Division of Neurology ( email )

Toronto, Ontario
Canada