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Background: Little is known about risk factors for mortality in older patients with COVID-19 and neuropsychiatric conditions., Methods: We conducted a multicentric retrospective observational study at Assistance Publique-Hôpitaux de Paris. We selected inpatients aged 70 years or older, with COVID-19 and preexisting neuropsychiatric comorbidities and/or new neuropsychiatric manifestations. We examined demographics, comorbidities, functional status, and presentation including neuropsychiatric symptoms and disorders, as well as paraclinical data. Cox survival analysis was conducted to determine risk factors for mortality at 40 days after the first symptoms of COVID-19., Results: Out of 191 patients included (median age 80 [interquartile range 74-87]), 135 (71%) had neuropsychiatric comorbidities including cognitive impairment (39%), cerebrovascular disease (22%), Parkinsonism (6%), and brain tumors (6%). A total of 152 (79%) patients presented new-onset neuropsychiatric manifestations including sensory symptoms (6%), motor deficit (11%), behavioral (18%) and cognitive (23%) disturbances, gait impairment (11%), and impaired consciousness (18%). The mortality rate at 40 days was 19.4%. A history of brain tumor or Parkinsonism or the occurrence of impaired consciousness were neurological factors associated with a higher risk of mortality. A lower Activities of Daily Living score (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.58-0.82), a neutrophil-to-lymphocyte ratio ≥ 9.9 (HR 5.69, 95% CI 2.69-12.0), and thrombocytopenia (HR 5.70, 95% CI 2.75-11.8) independently increased the risk of mortality (all p < .001)., Conclusion: Understanding mortality risk factors in older inpatients with COVID-19 and neuropsychiatric conditions may be helpful to neurologists and geriatricians who manage these patients in clinical practice., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

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., Competing Interests: TS is part of the Data Safety Monitoring Committee of a study to evaluate the safety and immunogenicity of a candidate Ebola Vaccine in children - the GSK3390107A (ChAd3 EBO-Z) vaccine; he is a panel member of Covid-19 Vaccine Benefit Risk Expert Working Group for the Medicines and Healthcare Regulatory Agency (UK); he is a member of COVID-19 Therapeutics Advisory Panel for the UK Department of Health & Social Care; he is the Chair/Co-Chair of the COVID-19 Rapid Response and Rolling Funding Initiatives, which supported the development of the Oxford-AstraZeneca Covid-19 vaccine. In addition, Dr. Solomon has a diagnostic test for bacterial meningitis, based on a blood test, filed for patent pending.

Purpose: Little is known about the neuronal substrates of neuropsychiatric symptoms associated with COVID-19 and their evolution during the course of the disease. We aimed at describing the longitudinal brain metabolic pattern in COVID-19-related encephalopathy using 18F-FDG-PET/CT., Methods: Seven patients with variable clinical presentations of COVID-19-related encephalopathy were explored thrice with brain 18F-FDG-PET/CT, once in the acute phase, 1 month later and 6 months after COVID-19 onset. PET images were analysed with voxel-wise and regions-of-interest approaches in comparison with 32 healthy controls., Results: Patients' neurological manifestations during acute encephalopathy were heterogeneous. However, all of them presented with predominant cognitive and behavioural frontal disorders. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. MRI revealed no specific abnormalities for most of the subjects. All patients had a consistent pattern of hypometabolism in a widespread cerebral network including the frontal cortex, anterior cingulate, insula and caudate nucleus. Six months after COVID-19 onset, the majority of patients clinically had improved but cognitive and emotional disorders of varying severity remained with attention/executive disabilities and anxio-depressive symptoms, and lasting prefrontal, insular and subcortical 18F-FDG-PET/CT abnormalities., Conclusion: The implication of this widespread network could be the neural substrate of clinical features observed in patients with COVID-19, such as frontal lobe syndrome, emotional disturbances and deregulation of respiratory failure perception. This study suggests that this network remains mildly to severely impaired 6 months after disease onset.

Objectives: To provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Methods: We conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March-April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible., Results: We included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53-72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19-associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19-associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischaemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%)., Conclusions: Clinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Importance: There is evidence of central nervous system impairments associated with coronavirus disease 2019 (COVID-19) infection, including encephalopathy. Multimodal monitoring of patients with COVID-19 may delineate the specific features of COVID-19-related encephalopathy and guide clinical management., Objectives: To investigate clinical, biological, and brain magnetic resonance imaging (MRI) findings in association with electroencephalographic (EEG) features for patients with COVID-19, and to better refine the features of COVID-19-related encephalopathy., Design, Setting, and Participants: This retrospective cohort study conducted in Pitié-Salpêtrière Hospital, Paris, France, enrolled 78 hospitalized adults who received a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and underwent EEG between March 30 and June 11, 2020., Exposures: Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay or, in the case of associated pneumonia, on a computed tomography scan of the chest., Main Outcomes and Measures: Data on the clinical and paraclinical features of the 78 patients with COVID-19 were retrieved from electronic patient records., Results: Of 644 patients who were hospitalized for COVID-19, 78 (57 men [73%]; mean [SD] age, 61 [12] years) underwent EEG. The main indications for EEG were delirium, seizure-like events, and delayed awakening in the intensive care unit after stopping treatment with sedatives. Sixty-nine patients showed pathologic EEG findings, including metabolic-toxic encephalopathy features, frontal abnormalities, periodic discharges, and epileptic activities. Of 57 patients who underwent brain MRI, 41 showed abnormalities, including perfusion abnormalities, acute ischemic lesions, multiple microhemorrhages, and white matter-enhancing lesions. Fifty-five patients showed biological abnormalities, including dysnatremia, kidney failure, and liver dysfunction, the same day as the EEG. The results of cerebrospinal fluid analysis were negative for SARS-Cov-2 for all tested patients. Nine patients who had no identifiable cause of brain injury outside COVID-19 were further isolated; their brain injury was defined as COVID-19-related encephalopathy. They represented 1% (9 of 644) of patients with COVID-19 requiring hospitalization. Six of these 9 patients had movement disorders, 7 had frontal syndrome, 4 had brainstem impairment, 4 had periodic EEG discharges, and 3 had MRI white matter-enhancing lesions., Conclusions and Relevance: The results from this cohort of patients hospitalized with COVID-19 suggest there are clinical, EEG, and MRI patterns that could delineate specific COVID-19-related encephalopathy and guide treatment strategy.

Soon after the pandemic, numerous publications described cases of neurological disorders associated with the SARS-CoV-2 infection. The range of neurological symptoms is becoming increasingly more extensive as the pandemic progresses. However, it is not yet well established whether the manifestations are due to direct viral damage to the nervous system or indirect consequences of the infection. This review presents an inventory of the biochemical markers studied in the context of neurological disorders related to SARS-CoV-2. By reflecting various physiopathological mechanisms, these biomarkers allow both a better understanding of the pathophysiology of Covid-19 and a contribution to the diagnosis of neurologic troubles; they could participate in the prognostic evaluation of patients.