Sung Min Cho 1, Nicole White 2, Lavienraj Premraj 3 4, Denise Battaglini 5 6, Jonathon Fanning 4 7, Jacky Suen 4 7, Gianluigi Li Bassi 2 4 7 8, John Fraser 2 4 7 9, Chiara Robba 5, Matthew Griffee 10, Bhagteshwar Singh 11 12 13, Barbara Wanjiru Citarella 14, Laura Merson 14, Tom Solomon 15 16 17, David Thomson 18 19, ISARIC Clinical Characterisation Group
1Neuroscience Critical Care Division, Departments of Neurology, Neurosurgery, and Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
2Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, School of Public Health & Social Work, Queensland University of Technology.
3Griffith University School of Medicine, Gold Coast, Australia.
4Critical Care Research Group, The Prince Charles Hospital, Brisbane, Australia.
5San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience, Department of Surgical Science and Integrated Diagnostic, University of Genoa, Genoa, Italy.
6Department of Medicine, University of Barcelona, Barcelona, Spain.
7Faculty of Medicine University of Queensland, Brisbane, Queensland, Australia.
8Institut d'Investigacions Biomediques August Pi I Sunyer, Barcelona, Spain.
9St Andrew's War Memorial Hospital, UnitingCare, Spring Hill, Queensland, Australia.
10Department of Anesthesiology, University of Utah, Salt Lake City, Utah.
11National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
12Tropical and Infectious Diseases Unit, Royal Liverpool.
13Broadgreen University Hospitals NHS Trust, Liverpool, United Kingdom; Christian Medical College, Vellore, India.
14International Severe Acute Respiratory and emerging Infections Consortium (ISARIC), Pandemic Sciences Institute, University of Oxford.
15Brain Infections Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
16Department of Neuroscience, University of Liverpool, Liverpool, UK.
17Walton Centre NHS Foundation Trust, Liverpool, UK.
18Department of Medicine, University of Cape Town, Cape Town, South Africa.
19Division of General Surgery, Groote Schuur Hospital, Cape Town, South Africa.
Correspondence to: Sung-Min Cho
Different neurological manifestations of 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 multicenter observational study using the International Severe Acute Respiratory and emerging Infection Consortium cohort across 1507 sites worldwide from January/30th/2020 to May/25th/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; 2,972 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 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 vs. non-ICU (7.1% vs. 2.3%, P < .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.