Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis
Singh B., Lant S., Cividini S., Cattrall JWS., Goodwin LC., Benjamin L., Michael BD., Khawaja A., Matos ADMB., Alkeridy W., Pilotto A., Lahiri D., Rawlinson R., Mhlanga S., Lopez EC., Sargent BF., Somasundaran A., Tamborska A., Webb G., Younas K., Al Sami Y., Babu H., Banks T., Cavallieri F., Cohen M., Davies E., Dhar S., Modol AF., Farooq H., Harte J., Hey S., Joseph A., Karthikappallil D., Kassahun D., Lipunga G., Mason R., Minton T., Mond G., Poxon J., Rabas S., Soothill G., Zedde M., Yenkoyan K., Brew B., Contini E., Cysique L., Zhang X., Maggi P., van Pesch V., Lechien J., Saussez S., Heyse A., Brito Ferreira ML., Soares CN., Elicer I., Eugenín-Von Bernhardi L., Reyes WÑ., Yin R., Azab MA., Abd-Allah F., Elkady A., Escalard S., Corvol JC., Delorme C., Tattevin P., Bigaut K., Lorenz N., Hornuss D., Hosp J., Rieg S., Wagner D., Knier B., Lingor P., Winkler AS., Sharifi-Razavi A., Moein ST., Seyed Alinaghi SA., Jamali Moghadam Siahkali S., Morassi M., Padovani A., Giunta M., Libri I., Beretta S., Ravaglia S., Foschi M., Calabresi P., Primiano G., Servidei S., Mercuri NB., Liguori C., Pierantozzi M., Sarmati L., Boso F., Garazzino S., Mariotto S., Patrick KN., Costache O., Pincherle A., Klok FA., Meza R.
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 We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute.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 Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease.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.