Neurological manifestations of COVID-19 in adults and children

ISARIC Clinical Characterisation Group; Sung-Min Cho; Nicole White; Lavienraj Premraj; Denise Battaglini; Jonathon Fanning; Jacky Suen; Gianluigi Li Bassi; John Fraser; Chiara Robba; Matthew Griffee; Bhagteshwar Singh; Barbara Wanjiru Citarella; Laura Merson; Tom Solomon; David Thomson

doi:10.1093/brain/awac332

Neurological manifestations of COVID-19 in adults and children

ISARIC Clinical Characterisation Group, Sung-Min Cho^*, Nicole White, Lavienraj Premraj, Denise Battaglini, Jonathon Fanning, Jacky Suen, Gianluigi Li Bassi, John Fraser, Chiara Robba, Matthew Griffee, Bhagteshwar Singh, Barbara Wanjiru Citarella, Laura Merson, Tom Solomon, David Thomson

^*Corresponding author for this work

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Abstract

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models.

Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001).

Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age.

In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

Original language	English
Pages (from-to)	1648–1661
Number of pages	14
Journal	Brain
Volume	146
Issue number	4
Early online date	10 Sept 2022
DOIs	https://doi.org/10.1093/brain/awac332
Publication status	Published - Apr 2023

Bibliographical note

Funding:
ISARIC4C is funded by National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059) and by the NIHR in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE; award 200907), NIHR HPRU at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013) and NIHR Clinical Research Network providing infrastructure support. ISARIC Global (B.W.C and L.M.) is funded by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z and 225288/Z/22/Z] and the Bill & Melinda Gates Foundation [OPP1209135]. S.M.C. is funded by NHLBI 1K23HL157610. N.W. was funded by an Advance Queensland Industry Research Fellowship (AQIRF076-2020-CV).

Keywords

COVID-19
neurological complication
stroke
seizure
meningitis
encephalitis

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Cite this

ISARIC Clinical Characterisation Group, Cho, S.-M., White, N., Premraj, L., Battaglini, D., Fanning, J., Suen, J., Bassi, G. L., Fraser, J., Robba, C., Griffee, M., Singh, B., Citarella, B. W., Merson, L., Solomon, T., & Thomson, D. (2023). Neurological manifestations of COVID-19 in adults and children. Brain, 146(4), 1648–1661. https://doi.org/10.1093/brain/awac332

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title = "Neurological manifestations of COVID-19 in adults and children",

abstract = "Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models.Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001).Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age.In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.",

keywords = "COVID-19, neurological complication, stroke, seizure, meningitis, encephalitis",

author = "{ISARIC Clinical Characterisation Group} and Sung-Min Cho and Nicole White and Lavienraj Premraj and Denise Battaglini and Jonathon Fanning and Jacky Suen and Bassi, {Gianluigi Li} and John Fraser and Chiara Robba and Matthew Griffee and Bhagteshwar Singh and Citarella, {Barbara Wanjiru} and Laura Merson and Tom Solomon and David Thomson and Christopher Green",

note = "Funding: ISARIC4C is funded by National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059) and by the NIHR in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE; award 200907), NIHR HPRU at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013) and NIHR Clinical Research Network providing infrastructure support. ISARIC Global (B.W.C and L.M.) is funded by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z and 225288/Z/22/Z] and the Bill & Melinda Gates Foundation [OPP1209135]. S.M.C. is funded by NHLBI 1K23HL157610. N.W. was funded by an Advance Queensland Industry Research Fellowship (AQIRF076-2020-CV).",

year = "2023",

month = apr,

doi = "10.1093/brain/awac332",

language = "English",

volume = "146",

pages = "1648–1661",

journal = "Brain",

issn = "0006-8950",

publisher = "Oxford University Press",

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TY - JOUR

T1 - Neurological manifestations of COVID-19 in adults and children

AU - ISARIC Clinical Characterisation Group

AU - Cho, Sung-Min

AU - White, Nicole

AU - Premraj, Lavienraj

AU - Battaglini, Denise

AU - Fanning, Jonathon

AU - Suen, Jacky

AU - Bassi, Gianluigi Li

AU - Fraser, John

AU - Robba, Chiara

AU - Griffee, Matthew

AU - Singh, Bhagteshwar

AU - Citarella, Barbara Wanjiru

AU - Merson, Laura

AU - Solomon, Tom

AU - Thomson, David

AU - Green, Christopher

N1 - Funding: ISARIC4C is funded by National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059) and by the NIHR in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE; award 200907), NIHR HPRU at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013) and NIHR Clinical Research Network providing infrastructure support. ISARIC Global (B.W.C and L.M.) is funded by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z and 225288/Z/22/Z] and the Bill & Melinda Gates Foundation [OPP1209135]. S.M.C. is funded by NHLBI 1K23HL157610. N.W. was funded by an Advance Queensland Industry Research Fellowship (AQIRF076-2020-CV).

PY - 2023/4

Y1 - 2023/4

N2 - Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models.Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001).Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age.In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

AB - Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models.Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001).Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age.In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

KW - COVID-19

KW - neurological complication

KW - stroke

KW - seizure

KW - meningitis

KW - encephalitis

U2 - 10.1093/brain/awac332

DO - 10.1093/brain/awac332

M3 - Article

SN - 0006-8950

VL - 146

SP - 1648

EP - 1661

JO - Brain

JF - Brain

IS - 4

ER -

Neurological manifestations of COVID-19 in adults and children

Abstract

Bibliographical note

Keywords

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