[en] [en] BACKGROUND: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome.
METHODS: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models.
RESULTS: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region.
INTERPRETATION: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.
Disciplines :
Otolaryngology
Author, co-author :
Singh, Bhagteshwar; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom ; Tropical and Infectious Diseases Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom ; Department of Infectious Diseases, Christian Medical College, Vellore, India
Lant, Suzannah; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
Cividini, Sofia ; Department of Health Data Science, University of Liverpool, Liverpool, United Kingdom
Cattrall, Jonathan W S; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
Goodwin, Lynsey C ; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom ; Tropical and Infectious Diseases Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom
Benjamin, Laura; Queen Square Institute of Neurology, University College London, London, United Kingdom
Michael, Benedict D; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom ; The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
Khawaja, Ayaz; Department of Neurology, Wayne State University, Detroit, Michigan, United States of America
Matos, Aline de Moura Brasil ; Instituto de Medicina Tropical, Universidade de São Paulo, São Paulo, Brazil
Alkeridy, Walid ; Department of Medicine, King Saud University, Riyadh, Saudi Arabia
Pilotto, Andrea; Department of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Brescia, Italy
Lahiri, Durjoy; Bangur Institute of Neurosciences, Institute of Post-Graduate Medical Education and Research, Kolkata, India
Rawlinson, Rebecca; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
Mhlanga, Sithembinkosi; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
Lopez, Evelyn C; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
Sargent, Brendan F; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
Somasundaran, Anushri; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
Tamborska, Arina; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
Webb, Glynn; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
Younas, Komal; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
Al Sami, Yaqub; Homerton University Hospital NHS Foundation Trust, London, United Kingdom of Great Britain and Northern Ireland
Babu, Heavenna; Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, India
Banks, Tristan; Department of Infection, Manchester University NHS Foundation Trust, Manchester, United Kingdom of Great Britain and Northern Ireland
Cavallieri, Francesco; Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
Cohen, Matthew; Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom of Great Britain and Northern Ireland
Davies, Emma; Department of Virology, UK Health Security Agency, Manchester University NHS Foundation Trust, Manchester, United Kingdom of Great Britain and Northern Ireland
Dhar, Shalley; Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, India
Fajardo Modol, Anna; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
Farooq, Hamzah; Department of Virology, UK Health Security Agency, Manchester University NHS Foundation Trust, Manchester, United Kingdom of Great Britain and Northern Ireland
Harte, Jeffrey; Barts Health NHS Trust, London, United Kingdom of Great Britain and Northern Ireland
Hey, Samuel; Department of Infectious Diseases & Tropical Medicine, North Manchester General Hospital, Manchester University Foundation NHS Trust, Manchester, United Kingdom of Great Britain and Northern Ireland
Joseph, Albert; Homerton University Hospital NHS Foundation Trust, London, United Kingdom of Great Britain and Northern Ireland
Karthikappallil, Dileep; Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom of Great Britain and Northern Ireland
Kassahun, Daniel; Warrington Hospital, Warrington and Halton Teaching Hospitals NHS Foundation Trust, Warrington, United Kingdom of Great Britain and Northern Ireland
Lipunga, Gareth; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
Mason, Rachel; Kingston Hospital NHS Foundation Trust, Kingston upon Thames, United Kingdom of Great Britain and Northern Ireland
Minton, Thomas; Institute of Clinical Neurosciences, University of Bristol, Bristol, United Kingdom of Great Britain and Northern Ireland
Mond, Gabrielle; North Manchester General Hospital, Manchester University Foundation NHS Trust, Manchester, United Kingdom of Great Britain and Northern Ireland
Poxon, Joseph; Epsom and St Helier University Hospitals NHS Foundation Trust, United Kingdom of Great Britain and Northern Ireland
Rabas, Sophie; King's College Hospital NHS Foundation Trust, London, United Kingdom of Great Britain and Northern Ireland
Soothill, Germander; Regional Infectious Diseases Unit, NHS Lothian, Edinburgh, United Kingdom of Great Britain and Northern Ireland
Zedde, Marialuisa; Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
Yenkoyan, Konstantin; Yerevan State Medical University named after Mkhitar Heratsi, Neuroscience Laboratory, Cobrain Center, Yerevan, Armenia
Brew, Bruce; St Vincent's Hospital, Sydney, Australia
Contini, Erika; St Vincent's Hospital, Sydney, Australia
Cysique, Lucette; St Vincent's Hospital, Sydney, Australia
Zhang, Xin; St Vincent's Hospital, Sydney, Australia
Maggi, Pietro; Saint-Luc University Hospital, Brussels, Belgium
van Pesch, Vincent; Saint-Luc University Hospital, Brussels, Belgium
Lechien, Jérome ; Université de Mons - UMONS > Faculté de Psychologie et des Sciences de l'Education > Service de Métrologie et Sciences du langage
Foschi, Matteo; Santa Maria delle Croci Hospital, AUSL Romagna, Ravenna, Italy
Calabresi, Paolo; Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
Primiano, Guido; Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
Servidei, Serenella; Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
Biagio Mercuri, Nicola; University Hospital of Rome Tor Vergata, Rome, Italy
Liguori, Claudio; University Hospital of Rome Tor Vergata, Rome, Italy
Pierantozzi, Mariangela; University Hospital of Rome Tor Vergata, Rome, Italy
Sarmati, Loredana; University Hospital of Rome Tor Vergata, Rome, Italy
Boso, Federica; Healthcare Trust of the Autonomous Region of Trento, Rovereto, Italy
Garazzino, Silvia; Città della Salute e della Scienza di Torino, Regina Margherita Children's Hospital, Turin, Italy
Mariotto, Sara; University of Verona, Verona, Italy
Patrick, Kimani N; Halcyon Healthcare Limited, Nairobi, Kenya
Costache, Oana; Hôpitaux Robert Schuman, Luxembourg, Luxembourg
Pincherle, Alexander; Hôpitaux Robert Schuman, Luxembourg, Luxembourg
Klok, Frederikus A; Leiden University Medical Center, Leiden, Netherlands
Meza, Roger; Hospital Regional Docente de Trujillo, Trujillo, Peru
Cabreira, Verónica; Centro Hospitalar São João, Porto, Portugal
Valdoleiros, Sofia R; Centro Hospitalar Universitário do Porto, Porto, Portugal
Oliveira, Vanessa; Centro Hospitalar Universitário do Porto, Porto, Portugal
Kaimovsky, Igor; Buyanov Moscow City Hospital, Moscow, Russian Federation
Guekht, Alla; Moscow Research and Clinical Center for Neuropsychiatry and Buyanov Moscow City Hospital, Moscow, Russian Federation
Koh, Jasmine; National Neuroscience Institute, Singapore, Singapore
Fernández Díaz, Eva; Complejo Hospitalario Universitario de Albacete, Albacete, Spain
Barrios-López, José María; Hospital Universitario Virgen de las Nieves, Granada, Spain
Guijarro-Castro, Cristina; University Hospital Sanchinarro, Madrid, Spain
Beltrán-Corbellini, Álvaro; University Hospital Ramón y Cajal, Madrid, Spain
Martínez-Poles, Javier; University Hospital Ramón y Cajal, Madrid, Spain
Diezma-Martín, Alba María; Hospital Virgen de la Salud, Toledo, Spain
Morales-Casado, Maria Isabel; Hospital Virgen de la Salud, Toledo, Spain
García García, Sergio; Hospital del Río Hortega, Valladolid, Spain
Breville, Gautier; Hopitaux Universitaires de Genève, Geneva, Switzerland
Coen, Matteo; Hopitaux Universitaires de Genève, Geneva, Switzerland
Uginet, Marjolaine; Hopitaux Universitaires de Genève, Geneva, Switzerland
Bernard-Valnet, Raphaël; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Du Pasquier, Renaud; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Kaya, Yildiz; Acibadem Mehmet Ali Aydinlar University Medical School, Istanbul, Turkey
Abdelnour, Loay H; Ulster Hospital, Belfast, United Kingdom of Great Britain and Northern Ireland
Rice, Claire; University of Bristol and North Bristol NHS Trust, Bristol, United Kingdom of Great Britain and Northern Ireland
Morrison, Hamish; Gloucestershire Royal Hospital, Gloucester, United Kingdom of Great Britain and Northern Ireland
Defres, Sylviane; Tropical and Infectious Diseases Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom
Huda, Saif; The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
Enright, Noelle; Great Ormond Street Hospital for Children, London, United Kingdom of Great Britain and Northern Ireland
Hassell, Jane; Great Ormond Street Hospital for Children, London, United Kingdom of Great Britain and Northern Ireland
D'Anna, Lucio; Imperial College London, London, United Kingdom of Great Britain and Northern Ireland
Benger, Matthew; King's College Hospital NHS Foundation Trust, London, United Kingdom of Great Britain and Northern Ireland
Sztriha, Laszlo; King's College Hospital NHS Foundation Trust, London, United Kingdom of Great Britain and Northern Ireland
Raith, Eamon; The National Hospital for Neurology & Neurosurgery, London, United Kingdom of Great Britain and Northern Ireland
Chinthapalli, Krishna; University College London, London, United Kingdom of Great Britain and Northern Ireland
Nortley, Ross; University College London, London, United Kingdom of Great Britain and Northern Ireland
Paterson, Ross; University College London, London, United Kingdom of Great Britain and Northern Ireland
Chandratheva, Arvind; University College London Queen Square Institute of Neurology, London, United Kingdom of Great Britain and Northern Ireland
Werring, David J; University College London Queen Square Institute of Neurology, London, United Kingdom of Great Britain and Northern Ireland
Dervisevic, Samir; Eastern Pathology Alliance Department of Microbiology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom of Great Britain and Northern Ireland
Harkness, Kirsty; Sheffield Teaching Hospitals Trust, Sheffield, United Kingdom of Great Britain and Northern Ireland
Pinto, Ashwin; Wessex Neurological Centre, Southampton, United Kingdom of Great Britain and Northern Ireland
Jillella, Dinesh; Emory University School of Medicine, Atlanta, Georgia, United States of America
Beach, Scott; Massachusetts General Hospital / Harvard Medical School, Boston, Massachusetts, United States of America
Gunasekaran, Kulothungan; Yale New Haven Health Bridgeport Hospital, Bridgeport, Connecticut, United States of America
Rocha Ferreira Da Silva, Ivan; Rush University Medical Center, Chicago, Illinois, United States of America
Nalleballe, Krishna; University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
Santoro, Jonathan; Children's Hospital Los Angeles and Keck School of Medicine at the University of Southern California, Los Angeles, California, United States of America
Scullen, Tyler; Ochsner Medical Center, New Orleans, Los Angeles, United States of America
Kahn, Lora; Ochsner Medical Center, New Orleans, Los Angeles, United States of America
Kim, Carla Y; Columbia University Irving Medical Center, New York, New York, United States of America
Thakur, Kiran T; Columbia University Irving Medical Center, New York, New York, United States of America
Jain, Rajan; New York University Grossman School of Medicine, New York, New York, United States of America
Umapathi, Thirugnanam; Department of Neurology, National Neuroscience Institute, Singapore, Singapore
Nicholson, Timothy R; Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom
Sejvar, James J; Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
Hodel, Eva Maria ; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
Brain Infections Global COVID-Neuro Network Study Group
Tudur Smith, Catrin; Department of Health Data Science, University of Liverpool, Liverpool, United Kingdom
Solomon, Tom ; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom ; Tropical and Infectious Diseases Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom ; The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
P362 - Métrologie et Sciences du langage M112 - Anatomie humaine et Oncologie expérimentale
Research institute :
R350 - Institut de recherche en sciences et technologies du langage R550 - Institut des Sciences et Technologies de la Santé
Funders :
Medical Research Council National Institute for Health Research National Institute for Health Research Horizon 2020
Funding text :
The study was funded by the UK Medical Research Council’s Global Effort on COVID-19 Programme (MR/V033441/1) (https://mrc.ukri.org/); UK National Institute for Health Research (NIHR)- funded Global Health Research Group on Acute Brain Infections (17/63/110) (https://www. nihr.ac.uk/); and the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections (NIHR200907), at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (Grant Nos. IS-HPU-1112-10117 and NIHR200907). These grants were awarded to TS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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