COVID-19 and neurologic manifestations: a synthesis from the child neurologist’s corner

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Since December 2019, the SARS-CoV-2 virus has been a global health issue. The main clinical presentation of this virus is a flu-like disease; however, patients with diverse neurologic manifestations have also been reported. In this review, we attempt to summarize, discuss and update the knowledge of the neurologic manifestations in the pediatric population affected by SARS-CoV-2 infection and the pandemic’s effects in children with neurologic diseases.

Data sources

This review analyzes studies found on the PubMed database using the following keywords: Neurologic manifestations COVID-19, Neurological COVID-19, coronavirus, SARS-CoV-2, pediatric COVID-19, COVID-19 in children, MIS-C, Pediatric Inflammatory Multisystem Syndrome, Guillain Barré Syndrome, Stroke, ADEM, and Anti-NMDA encephalitis. All studies cited were published between 2004 and 2022, and represent the most relevant articles in the field. The World Health Organization COVID-19 online dashboard was assessed to obtain updated epidemiological data.

Results

The most common neurologic symptoms in the pediatric population are headache, seizures, encephalopathy, and muscle weakness. These can be present during COVID-19 or weeks after recovering from it. Children who presented with multi-system inflammatory syndrome had a higher incidence of neurologic manifestations, which conferred a greater risk of morbidity and mortality. Several neuro-pathophysiological mechanisms have been proposed, including direct virus invasion, hyper-inflammatory reactions, multi-systemic failure, prothrombotic states, and immune-mediated processes. On the other hand, the COVID-19 pandemic has affected patients with neurologic diseases, making it challenging to access controls, treatment, and therapies.

Conclusions

Various neurologic manifestations have been associated with children’s SARS-CoV-2 infection. It is important to identify and give them proper and opportune treatment because they can be potentially grave and life-threatening; some can lead to long-lasting sequelae. Different neuro-pathophysiological mechanisms have been proposed, however, a causal relationship between SARS-CoV-2 infection and neurologic manifestations remains to be proven. Patients with neurologic diseases are especially affected by COVID-19, not only by the disease itself but also by its complications and pandemic management measures.

Related collections

Most cited references 113

Record: found
Abstract: found
Article: found

Neurological associations of COVID-19

Mark Ellul, Laura Benjamin, Bhagteshwar Singh … (2020)

Summary Background The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare. Recent developments A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2–6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin. Where next? Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.

0 comments Cited 1127 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

A first case of meningitis/encephalitis associated with SARS-Coronavirus-2

Takeshi Moriguchi, Norikazu Harii, Junko Goto … (2020)

Highlights • Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly. • This is the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance. • The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF. • This case warns the physicians of patients who have CNS symptoms.

0 comments Cited 1064 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records

Maxime Taquet, John R Geddes, Masud Husain … (2021)

Background Neurological and psychiatric sequelae of COVID-19 have been reported, but more data are needed to adequately assess the effects of COVID-19 on brain health. We aimed to provide robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis. Methods For this retrospective cohort study and time-to-event analysis, we used data obtained from the TriNetX electronic health records network (with over 81 million patients). Our primary cohort comprised patients who had a COVID-19 diagnosis; one matched control cohort included patients diagnosed with influenza, and the other matched control cohort included patients diagnosed with any respiratory tract infection including influenza in the same period. Patients with a diagnosis of COVID-19 or a positive test for SARS-CoV-2 were excluded from the control cohorts. All cohorts included patients older than 10 years who had an index event on or after Jan 20, 2020, and who were still alive on Dec 13, 2020. We estimated the incidence of 14 neurological and psychiatric outcomes in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root, and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders (grouped and separately); substance use disorder; and insomnia. Using a Cox model, we compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory tract infections. We investigated how these estimates were affected by COVID-19 severity, as proxied by hospitalisation, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders). We assessed the robustness of the differences in outcomes between cohorts by repeating the analysis in different scenarios. To provide benchmarking for the incidence and risk of neurological and psychiatric sequelae, we compared our primary cohort with four cohorts of patients diagnosed in the same period with additional index events: skin infection, urolithiasis, fracture of a large bone, and pulmonary embolism. Findings Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% (95% CI 33·17–34·07), with 12·84% (12·36–13·33) receiving their first such diagnosis. For patients who had been admitted to an ITU, the estimated incidence of a diagnosis was 46·42% (44·78–48·09) and for a first diagnosis was 25·79% (23·50–28·25). Regarding individual diagnoses of the study outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% (0·50–0·63) for intracranial haemorrhage, 2·10% (1·97–2·23) for ischaemic stroke, 0·11% (0·08–0·14) for parkinsonism, 0·67% (0·59–0·75) for dementia, 17·39% (17·04–17·74) for anxiety disorder, and 1·40% (1·30–1·51) for psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2·66% (2·24–3·16) for intracranial haemorrhage, 6·92% (6·17–7·76) for ischaemic stroke, 0·26% (0·15–0·45) for parkinsonism, 1·74% (1·31–2·30) for dementia, 19·15% (17·90–20·48) for anxiety disorder, and 2·77% (2·31–3·33) for psychotic disorder. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio [HR] 1·44, 95% CI 1·40–1·47, for any diagnosis; 1·78, 1·68–1·89, for any first diagnosis) and those who had other respiratory tract infections (1·16, 1·14–1·17, for any diagnosis; 1·32, 1·27–1·36, for any first diagnosis). As with incidences, HRs were higher in patients who had more severe COVID-19 (eg, those admitted to ITU compared with those who were not: 1·58, 1·50–1·67, for any diagnosis; 2·87, 2·45–3·35, for any first diagnosis). Results were robust to various sensitivity analyses and benchmarking against the four additional index health events. Interpretation Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19. This information could help in service planning and identification of research priorities. Complementary study designs, including prospective cohorts, are needed to corroborate and explain these findings. Funding National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre.

0 comments Cited 1013 times – based on 0 reviews      Review now

All references

Author and article information

Contributors

Francisca Sandoval:

ORCID: http://orcid.org/0000-0003-3919-9240

francisca.sandoval.alvarez@gmail.com

Journal

Journal ID (nlm-ta): World J Pediatr

Journal ID (iso-abbrev): World J Pediatr

Title: World Journal of Pediatrics

Publisher: Springer Nature Singapore (Singapore )

ISSN (Print): 1708-8569

ISSN (Electronic): 1867-0687

Publication date (Electronic): 27 April 2022

Pages: 1-10

Affiliations

Department of Neurology, Hospital Dr. Exequiel González Cortés, Gran Avenida José Miguel Carrera 3300, 8900085 Santiago, Región Metropolitana Chile

Author information

Gastón Méndez http://orcid.org/0000-0002-4421-4428

Francisca Sandoval http://orcid.org/0000-0003-3919-9240

Article

Publisher ID: 550

DOI: 10.1007/s12519-022-00550-4

PMC ID: 9044375

PubMed ID: 35476245

SO-VID: ca668024-fe41-46d8-bc1a-59211ad73c51

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

COVID-19 and neurologic manifestations: a synthesis from the child neurologist’s corner

Read this article at

Abstract

Background

Data sources

Results

Conclusions

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 113

Neurological associations of COVID-19

A first case of meningitis/encephalitis associated with SARS-Coronavirus-2

6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Categories

Comments

Comment on this article

Similar content 18

Cited by 22

Most referenced authors 2,181