Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barre syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

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The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.

Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.

Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic spreads, it is becoming increasingly evident that coronavirus disease 2019 (COVID-19) is not limited to the respiratory system, and that other organs can be affected. In particular, virus-related neurological manifestations are being reported more and more frequently in the scientific literature. In this article, we review the literature on the association between COVID-19 and neurological manifestations, present evidence from preclinical research suggesting that SARS-CoV-2 could be responsible for many of these manifestations, and summarize the biological pathways that could underlie each neurological symptom. Understanding the mechanisms that lead to neurological manifestations in patients with COVID-19 and how these manifestations correlate with clinical outcomes will be instrumental in guiding the optimal use of targeted therapeutic strategies.

/pdf/lifting-the-mask-on-neurological-manifestations-of-covid-19-1kisupaknm.pdf

Lifting the mask on neurological manifestations of COVID-19.

Case studies have revealed neurological problems in severely affected COVID-19 patients. However, there is little information regarding the nature and broader prevalence of cognitive problems post-infection or across the full spread of severity. We analysed cognitive test data from 84,285 Great British Intelligence Test participants who completed a questionnaire regarding suspected and biologically confirmed COVID-19 infection. People who had recovered, including those no longer reporting symptoms, exhibited significant cognitive deficits when controlling for age, gender, education level, income, racial-ethnic group and pre-existing medical disorders. They were of substantial effect size for people who had been hospitalised, but also for mild but biologically confirmed cases who reported no breathing difficulty. Finer grained analyses of performance support the hypothesis that COVID-19 has a multi-system impact on human cognition. Significance statement There is evidence that COVID-19 may cause long term health changes past acute symptoms, termed ‘long COVID’. Our analyses of detailed cognitive assessment and questionnaire data from tens thousands of datasets, collected in collaboration with BBC2 Horizon, align with the view that there are chronic cognitive consequences of having COVID-19. Individuals who recovered from suspected or confirmed COVID-19 perform worse on cognitive tests in multiple domains than would be expected given their detailed age and demographic profiles. This deficit scales with symptom severity and is evident amongst those without hospital treatment. These results should act as a clarion call for more detailed research investigating the basis of cognitive deficits in people who have survived SARS-COV-2 infection.

https://medrxiv.org/content/10.1101/2020.10.20.20215863v1.full.pdf

Cognitive deficits in people who have recovered from COVID-19 relative to controls: An N=84,285 online study

Cognitive deficits in people who have recovered from COVID-19.

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were (a) positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, (b) severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, (c) neurologic manifestations, and (d) abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student t test or Wilcoxon test. P < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], P = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], P = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.

https://pubs.rsna.org/doi/pdf/10.1148/radiol.2020202222

Véronique Mutschler

Papers

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.