PLoS ONE (Jan 2022)

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

  • Bhagteshwar Singh,
  • Suzannah Lant,
  • Sofia Cividini,
  • Jonathan W. S. Cattrall,
  • Lynsey C. Goodwin,
  • Laura Benjamin,
  • Benedict D. Michael,
  • Ayaz Khawaja,
  • Aline de Moura Brasil Matos,
  • Walid Alkeridy,
  • Andrea Pilotto,
  • Durjoy Lahiri,
  • Rebecca Rawlinson,
  • Sithembinkosi Mhlanga,
  • Evelyn C. Lopez,
  • Brendan F. Sargent,
  • Anushri Somasundaran,
  • Arina Tamborska,
  • Glynn Webb,
  • Komal Younas,
  • Yaqub Al Sami,
  • Heavenna Babu,
  • Tristan Banks,
  • Francesco Cavallieri,
  • Matthew Cohen,
  • Emma Davies,
  • Shalley Dhar,
  • Anna Fajardo Modol,
  • Hamzah Farooq,
  • Jeffrey Harte,
  • Samuel Hey,
  • Albert Joseph,
  • Dileep Karthikappallil,
  • Daniel Kassahun,
  • Gareth Lipunga,
  • Rachel Mason,
  • Thomas Minton,
  • Gabrielle Mond,
  • Joseph Poxon,
  • Sophie Rabas,
  • Germander Soothill,
  • Marialuisa Zedde,
  • Konstantin Yenkoyan,
  • Bruce Brew,
  • Erika Contini,
  • Lucette Cysique,
  • Xin Zhang,
  • Pietro Maggi,
  • Vincent van Pesch,
  • Jérome Lechien,
  • Sven Saussez,
  • Alex Heyse,
  • Maria Lúcia Brito Ferreira,
  • Cristiane N. Soares,
  • Isabel Elicer,
  • Laura Eugenín-von Bernhardi,
  • Waleng Ñancupil Reyes,
  • Rong Yin,
  • Mohammed A. Azab,
  • Foad Abd-Allah,
  • Ahmed Elkady,
  • Simon Escalard,
  • Jean-Christophe Corvol,
  • Cécile Delorme,
  • Pierre Tattevin,
  • Kévin Bigaut,
  • Norbert Lorenz,
  • Daniel Hornuss,
  • Jonas Hosp,
  • Siegbert Rieg,
  • Dirk Wagner,
  • Benjamin Knier,
  • Paul Lingor,
  • Andrea Sylvia Winkler,
  • Athena Sharifi-Razavi,
  • Shima T. Moein,
  • SeyedAhmad SeyedAlinaghi,
  • Saeidreza JamaliMoghadamSiahkali,
  • Mauro Morassi,
  • Alessandro Padovani,
  • Marcello Giunta,
  • Ilenia Libri,
  • Simone Beretta,
  • Sabrina Ravaglia,
  • Matteo Foschi,
  • Paolo Calabresi,
  • Guido Primiano,
  • Serenella Servidei,
  • Nicola Biagio Mercuri,
  • Claudio Liguori,
  • Mariangela Pierantozzi,
  • Loredana Sarmati,
  • Federica Boso,
  • Silvia Garazzino,
  • Sara Mariotto,
  • Kimani N. Patrick,
  • Oana Costache,
  • Alexander Pincherle,
  • Frederikus A. Klok,
  • Roger Meza,
  • Verónica Cabreira,
  • Sofia R. Valdoleiros,
  • Vanessa Oliveira,
  • Igor Kaimovsky,
  • Alla Guekht,
  • Jasmine Koh,
  • Eva Fernández Díaz,
  • José María Barrios-López,
  • Cristina Guijarro-Castro,
  • Álvaro Beltrán-Corbellini,
  • Javier Martínez-Poles,
  • Alba María Diezma-Martín,
  • Maria Isabel Morales-Casado,
  • Sergio García García,
  • Gautier Breville,
  • Matteo Coen,
  • Marjolaine Uginet,
  • Raphaël Bernard-Valnet,
  • Renaud Du Pasquier,
  • Yildiz Kaya,
  • Loay H. Abdelnour,
  • Claire Rice,
  • Hamish Morrison,
  • Sylviane Defres,
  • Saif Huda,
  • Noelle Enright,
  • Jane Hassell,
  • Lucio D’Anna,
  • Matthew Benger,
  • Laszlo Sztriha,
  • Eamon Raith,
  • Krishna Chinthapalli,
  • Ross Nortley,
  • Ross Paterson,
  • Arvind Chandratheva,
  • David J. Werring,
  • Samir Dervisevic,
  • Kirsty Harkness,
  • Ashwin Pinto,
  • Dinesh Jillella,
  • Scott Beach,
  • Kulothungan Gunasekaran,
  • Ivan Rocha Ferreira Da Silva,
  • Krishna Nalleballe,
  • Jonathan Santoro,
  • Tyler Scullen,
  • Lora Kahn,
  • Carla Y. Kim,
  • Kiran T. Thakur,
  • Rajan Jain,
  • Thirugnanam Umapathi,
  • Timothy R. Nicholson,
  • James J. Sejvar,
  • Eva Maria Hodel,
  • The Brain Infections Global COVID-Neuro Network Study Group,
  • Catrin Tudur Smith,
  • Tom Solomon

Journal volume & issue
Vol. 17, no. 6

Abstract

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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.