Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis
Authors: Singh Bhagteshwar , Lant Suzannah , Cividini Sofia , Cattrall Jonathan W. S. , Goodwin Lynsey C. , Benjamin Laura , Michael Benedict D. , Khawaja Ayaz , Matos Aline de Moura Brasil , Alkeridy Walid , Pilotto Andrea , Lahiri Durjoy , Rawlinson Rebecca , Mhlanga Sithembinkosi , Lopez Evelyn C. , Sargent Brendan F. , Somasundaran Anushri , Tamborska Arina , Webb Glynn , Younas Komal , Al Sami Yaqub , Babu Heavenna , Banks Tristan , Cavallieri Francesco , Cohen Matthew , Davies Emma , Dhar Shalley , Fajardo Modol Anna , Farooq Hamzah , Harte Jeffrey , Hey Samuel , Joseph Albert , Karthikappallil Dileep , Kassahun Daniel , Lipunga Gareth , Mason Rachel , Minton Thomas , Mond Gabrielle , Poxon Joseph , Rabas Sophie , Soothill Germander , Zedde Marialuisa , Yenkoyan Konstantin , Brew Bruce , Contini Erika , Cysique Lucette , Zhang Xin , Maggi Pietro , van Pesch Vincent , Lechien Jérome , Saussez Sven , Heyse Alex , Brito Ferreira Maria Lúcia , Soares Cristiane N. , Elicer Isabel , Eugenín-von Bernhardi Laura , Ñancupil Reyes Waleng , Yin Rong , Azab Mohammed A. , Abd-Allah Foad , Elkady Ahmed , Escalard Simon , Corvol Jean-Christophe , Delorme Cécile , Tattevin Pierre , Bigaut Kévin , Lorenz Norbert , Hornuss Daniel , Hosp Jonas , Rieg Siegbert , Wagner Dirk , Knier Benjamin , Lingor Paul , Winkler Andrea Sylvia , Sharifi-Razavi Athena , Moein Shima T. , SeyedAlinaghi SeyedAhmad , JamaliMoghadamSiahkali Saeidreza , Morassi Mauro , Padovani Alessandro , Giunta Marcello , Libri Ilenia , Beretta Simone , Ravaglia Sabrina , Foschi Matteo , Calabresi Paolo , Primiano Guido , Servidei Serenella , Biagio Mercuri Nicola , Liguori Claudio , Pierantozzi Mariangela , Sarmati Loredana , Boso Federica , Garazzino Silvia , Mariotto Sara , Patrick Kimani N. , Costache Oana , Pincherle Alexander , Klok Frederikus A. , Meza Roger , Cabreira Verónica , Valdoleiros Sofia R. , Oliveira Vanessa , Kaimovsky Igor , Guekht Alla , Koh Jasmine , Fernández Díaz Eva , Barrios-López José María , Guijarro-Castro Cristina , Beltrán-Corbellini Álvaro , Martínez-Poles Javier , Diezma-Martín Alba María , Morales-Casado Maria Isabel , García García Sergio , Breville Gautier , Coen Matteo , Uginet Marjolaine , Bernard-Valnet Raphaël , Du Pasquier Renaud , Kaya Yildiz , Abdelnour Loay H. , Rice Claire , Morrison Hamish , Defres Sylviane , Huda Saif , Enright Noelle , Hassell Jane , D’Anna Lucio , Benger Matthew , Sztriha Laszlo , Raith Eamon , Chinthapalli Krishna , Nortley Ross , Paterson Ross , Chandratheva Arvind , Werring David J. , Dervisevic Samir , Harkness Kirsty , Pinto Ashwin , Jillella Dinesh , Beach Scott , Gunasekaran Kulothungan , Rocha Ferreira Da Silva Ivan , Nalleballe Krishna , Santoro Jonathan , Scullen Tyler , Kahn Lora , Kim Carla Y. , Thakur Kiran T. , Jain Rajan , Umapathi Thirugnanam , Nicholson Timothy R. , Sejvar James J. , Hodel Eva Maria ,   The Brain Infections Global COVID-Neuro Network Study Group, Tudur Smith Catrin , Solomon Tom 
Published: June 2022

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.