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Neurological Presentations and In-Hospital Complications of COVID-19 in Adults and Children: A Large Prospective Multicentre Observational Study from the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)

46 Pages Posted: 6 Apr 2022

See all articles by Sung-Min Cho

Sung-Min Cho

Johns Hopkins University - Neuroscience Critical Care Division

Nicole White

Macquarie University - Australian Institute of Health Innovation

Lavienraj Premraj

Griffith University - School of Medicine

Denise Battaglini

University of Genova - Department of Surgical Science and Integrated Diagnostics (DISC)

Jonathon P. Fanning

University of Queensland - Prince Charles Hospital

Jacky Y. Suen

University of Queensland

Gianluigi Li Bassi

University of Queensland - Critical Care Research Group

John Fraser

University of Queensland - Critical Care Research Group

Chiara Robba

Università degli Studi di Genova

Matthew Griffee

University of Utah Health

Bhagteshwar Singh

University of Liverpool

Tom Solomon

University of Liverpool - Institute of Infection and Global Health

David Thomson

University of Cape Town (UCT) - Groote Schuur Hospital

ISARIC Clinical Characterisation Group

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Abstract

Background The neurological manifestations of COVID-19 have not been well characterized. Our goals were to determine the prevalence of neurological diagnoses among COVID-19 patients hospitalized in intensive care unit (ICU) and non-ICU settings and ascertain differences between adults and children. 

Methods We analysed the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) database, which collects data from 61 countries and 1507 sites. 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 hospitalisation using generalised linear models. 

Findings Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 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%). Among adults, rates were significantly higher in the ICU cohort than in the non-ICU cohort for myalgia (19·9% vs. 16·1%, p<0·001) and anosmia (6·3% vs. 5·9%, p=0·01) but lower in the ICU cohort for altered consciousness (10·8% vs. 24%, p<0·001) and seizure (0·8% vs. 1·2%, p<0·001). In children, rates were significantly higher in the ICU cohort than in the non-ICU cohort for fatigue (30·4% vs. 18·7%, p<0·001), myalgia (12·8% vs. 6·7%, p<0·001), and altered consciousness (12% vs. 5·7%, p<0·001). In adults, the most frequent in-hospital neurological complications were stroke (1·5%), seizure (1%), and central nervous system (CNS) infection (0·2%). Each occurred more frequently in ICU than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU than in non-ICU patients (7·1 vs. 2·3, p<0·001). 

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 neurological complications reported during hospitalisation were associated with increased odds of death. 

Interpretation Adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Hypertension and previous neurological disease are risk factors for in-hospital neurological complications, which are associated with an increased probability of death in both adults and children.

Funding Information: ISARIC4C is funded by two major awards from UK Research and Innovation (UKRI) and The National Institute for Health Research (NIHR). S.M.C. is funded by NHLBI 1K23HL157610. N.W. was funded by an Advance Queensland Industry Research Fellowship (AQIRF076-2020-CV).

Declaration of Interests: None to declare.

Ethics Approval Statement: The study was approved by the World Health Organization Ethics Review Committee (RPC571 and RPC572). Local ethics approval was obtained for each participating country and site according to local requirements.

Keywords: COVID-19, SARS-CoV-2, adults, children, neurological presentation, neurological complication, stroke, seizure, meningitis, encephalitis.

Suggested Citation

Cho, Sung-Min and White, Nicole and Premraj, Lavienraj and Battaglini, Denise and Fanning, Jonathon P. and Suen, Jacky Y. and Li Bassi, Gianluigi and Fraser, John and Robba, Chiara and Griffee, Matthew and Singh, Bhagteshwar and Solomon, Tom and Thomson, David and Group, ISARIC Clinical Characterisation, Neurological Presentations and In-Hospital Complications of COVID-19 in Adults and Children: A Large Prospective Multicentre Observational Study from the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). Available at SSRN: https://ssrn.com/abstract=4047877 or http://dx.doi.org/10.2139/ssrn.4047877

Sung-Min Cho (Contact Author)

Johns Hopkins University - Neuroscience Critical Care Division ( email )

United States

Nicole White

Macquarie University - Australian Institute of Health Innovation ( email )

Sydney
Australia

Lavienraj Premraj

Griffith University - School of Medicine ( email )

Denise Battaglini

University of Genova - Department of Surgical Science and Integrated Diagnostics (DISC) ( email )

Jonathon P. Fanning

University of Queensland - Prince Charles Hospital ( email )

Jacky Y. Suen

University of Queensland ( email )

St Lucia
Brisbane, Queensland 4072
Australia

Gianluigi Li Bassi

University of Queensland - Critical Care Research Group ( email )

627 Rode Rd
Chermside QLD 4032
Australia

John Fraser

University of Queensland - Critical Care Research Group ( email )

Chiara Robba

Università degli Studi di Genova ( email )

Via Vivaldi 5
Genova, 16126
Italy

Matthew Griffee

University of Utah Health ( email )

Salt Lake City, UT
United States

Bhagteshwar Singh

University of Liverpool ( email )

Chatham Street
Brownlow Hill
Liverpool, L69 7ZA
United Kingdom

Tom Solomon

University of Liverpool - Institute of Infection and Global Health ( email )

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

David Thomson

University of Cape Town (UCT) - Groote Schuur Hospital ( email )

South Africa

No contact information is available for ISARIC Clinical Characterisation Group