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

Abstract

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 We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute.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 Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease.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.

COVID-19 and Parkinsonism: A Critical Appraisal

“…In particular, considering that it might be difficult to differentiate between the second and third scenarios, only patients who satisfied the criteria for COVID-19-related encephalitis/encephalopathies proposed in a recent individual patient data meta-analysis [ 15 ] were included in the “extensive inflammation or hypoxic brain injury within the context of encephalopathy” group. This allowed us to also include in the “unmasking of underlying still non-symptomatic PD” scenario only patients with no clinical or instrumental signs of extensive inflammation of the brain within the context of encephalitis/encephalopathies, particularly confirmed by the absence of brain MRI pathological changes.…”

Critical care management of meningitis and encephalitis: an update

“…A recent individual patient data meta-analysis of 1979 hospitalized patients with neurological COVID-19 from 83 studies showed that poor outcome corresponding to moderate-to-severe disability or death (mRS 3–6) was more common in patients with cerebrovascular events (76%), than encephalopathy (54%) [47].…”

Acute encephalopathy in a 6-year-old child with concurrent COVID-19 infection: a case report from Saudi Arabia

“…Although most of these severe manifestations have been reported in adult patients, few pediatric patients have such complications (Akın et al, 2021, Gaughan et al, 2021, Vraka et al, 2021. Based on a recent published meta-analysis the authors found that in patients with COVID-19-induced encephalopathy, age 70-79 years, low admission lymphocyte counts, and use of corticosteroid and anticoagulants are considered poor prognostic factors (Singh et al, 2022). On the other hand, data about the pediatric COVID-19-induced encephalopathy are scare, and most of the available data are based on case reports and few case series (Gaughan et al, 2021, McAbee et al, 2020.…”

“…Although the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory system, neurological manifestations, including encephalopathy, have been reported in some patients (Akın et al, 2021, Lin et al, 2020, McAbee et al, 2020, Singh et al, 2022, Vraka et al, 2021. The first case of meningoencephalitis associated with SARS-CoV-2 infection was reported in an adult patient in March 2020, with a positive specific SARS-CoV-2 ribonucleic acid (RNA) in the cerebrospinal fluid (CSF) (Poyiadji et al, 2020).…”