Comparative features and outcomes of major neurological complications of COVID-19
31 October 2022
Authors: Ettore Beghi, Elena Moro, Eugenia Irene Davidescu, Bogdan Ovidiu Popescu, Oxana Grosu … Claudio L. A. Bassetti
Background and purpose:
The aim of this study was to assess the neurological com-plications of SARS-CoV- 2 infection and compare phenotypes and outcomes in infected patients with and without selected neurological manifestations.
The data source was a registry established by the European Academy of Neurology during the first wave of the COVID-19 pandemic. Neurologists collected data on patients with COVID-19 seen as in- and outpatients and in emergency rooms in 23 European and seven non-European countries. Prospective and retrospective data included patient demographics, lifestyle habits, comorbidities, main COVID-19 complica-tions, hospital and intensive care unit admissions, diagnostic tests, and outcome. Acute/subacute selected neurological manifestations in patients with COVID-19 were analysed, comparing individuals with and without each condition for several risk factors.
By July 31, 2021, 1523 patients (758 men, 756 women, and nine intersex/un-known, aged 16–101 years) were registered. Neurological manifestations were diagnosed in 1213 infected patients (79.6%). At study entry, 978 patients (64.2%) had one or more chronic general or neurological comorbidities. Predominant acute/subacute neurological manifestations were cognitive dysfunction (N= 449, 29.5%), stroke (N= 392, 25.7%), sleep– wake disturbances (N= 250, 16.4%), dysautonomia (N= 224, 14.7%), peripheral neuropathy (N= 145, 9.5%), movement disorders (N= 142, 9.3%), ataxia (N= 134, 8.8%), and seizures (N= 126, 8.3%). These manifestations tended to differ with regard to age, general and neurological comorbidities, infection severity and non- neurological manifes-tations, extent of association with other acute/subacute neurological manifestations, and outcome.
Patients with COVID-19 and neurological manifestations present with dis-tinct phenotypes. Differences in age, general and neurological comorbidities, and infec-tion severity characterize the various neurological manifestations of COVID-19
COVID-19 vaccination hesitancy among people with chronic neurological disorders: a position paper
23 April 2022
Martin Rakusa, Serefnur Öztürk, Elena Moro, Raimund Helbok, Claudio L. Bassetti, Ettore Beghi... Johann Sellner
Health risks associated with SARS-CoV-2 infection are undisputed. Moreover, the capability of vaccination to prevent symptomatic, severe and fatal COVID-19 is recognized. There is also early evidence that vaccination can reduce the chance for long COVID-19. Nonetheless, the willingness to get vaccinated and receive booster shots remains subpar among people with neurologic disorders. Vaccine scepticism not only jeopardizes collective efforts to end the COVID-19 pandemic but puts individual lives at risk as some chronic neurologic diseases are associated with a higher risk for an unfavorable COVID-19 course.
In this position paper, the NeuroCOVID-19 Task Force of the European Academy of Neurology (EAN) summarizes the current knowledge on the prognosis of COVID-19 among patients with neurologic disease, elucidates potential barriers to vaccination coverage and formulates strategies to overcome vaccination hesitancy. A survey among the task force members on the phenomenon of vaccination hesitancy among people with neurologic disease supports the lines of argumentation.
The study revealed that people with multiple sclerosis and other nervous system autoimmune disorders are most skeptical of SARS-CoV-2 vaccination. The prevailing concerns included the chance of worsening the pre-existing neurological condition, vaccination-related adverse events, and drug interaction.
The EAN NeuroCOVID-19 task force reinforces the key role of neurologists as advocates of COVID-19 vaccination. Neurologists need to argue in the interest of their patients about the overwhelming individual and global benefits of COVID-19 vaccination. Moreover, they need to keep on eye on this vulnerable patient group, their concerns and the emergence of potential safety signals.
Short- and long-term outcome and predictors in an international cohort of patients with neuro-COVID-19
23 February 2022
Ettore Beghi, Raimund Helbok, Serefnur Oztturk, Omer Karadas, Vitalie Lisnic, Oxana Grosu... Claudio L. A. Bassetti, https://doi.org/10.1111/ene.15293
Background and purpose
Despite the increasing number of reports on the spectrum of neurological manifestations of COVID-19 (neuro-COVID), few studies have assessed short- and long-term outcome of the disease.
This is a cohort study enrolling adult patients with neuro-COVID seen in neurological consultation. Data were collected prospectively or retrospectively in the European Academy of Neurology NEuro-covid ReGistrY ((ENERGY). The outcome at discharge was measured using the modified Rankin Scale and defined as ‘stable/improved’ if the modified Rankin Scale score was equal to or lower than the pre-morbid score, ‘worse’ if the score was higher than the pre-morbid score. Status at 6 months was also recorded. Demographic and clinical variables were assessed as predictors of outcome at discharge and 6 months.
From July 2020 to March 2021, 971 patients from 19 countries were included. 810 (83.4%) were hospitalized. 432 (53.3%) were discharged with worse functional status. Older age, stupor/coma, stroke and intensive care unit (ICU) admission were predictors of worse outcome at discharge. 132 (16.3%) died in hospital. Older age, cancer, cardiovascular complications, refractory shock, stupor/coma and ICU admission were associated with death. 262 were followed for 6 months. Acute stroke or ataxia, ICU admission and degree of functional impairment at discharge were predictors of worse outcome. 65/221 hospitalized patients (29.4%) and 10/32 non-hospitalized patients (24.4%) experienced persisting neurological symptoms/signs. 10/262 patients (3.8%) developed new neurological complaints during the 6 months of follow-up.
Neuro-COVID is a severe disease associated with worse functional status at discharge, particularly in older subjects and those with comorbidities and acute complications of infection.
Lessons learned from people with neurological diseases at the time of COVID-19: The EFNA-EAN survey
30 August 2021
Benedetta Bodini, Elena Moro, Joke Jaarsma, Elizabeth Cunningham, Johann Sellner, Donna Walsh, on behalf of the EANcore COVID-19 Task Force
Background and purpose
The European Federation of Neurological Associations (EFNA), in partnership with the NeuroCOVID-19 taskforce of the European Academy of Neurology (EAN), has investigated the impact of the first wave of the COVID-19 pandemic on individuals with neurological diseases, as well as the hopes and fears of these patients about the post-pandemic phase.
An EFNA-EAN survey was available online to any person living with a neurological disorder in Europe. It consisted of 18 items concerning the impact of the first wave of the COVID-19 pandemic on the medical care of people with neurological disorders, and the hopes and fears of these individuals regarding the post-pandemic phase.
For 44.4% of the 443 survey participants, the overall care of their neurological disease during the pandemic was inappropriate. This perception was mainly due to significant delays in accessing medical care (25.7%), insufficiently reliable information received about the potential impact of COVID-19 on their neurological disease (49.6%), and a substantial lack of involvement in their disease management decisions (54.3%). Participants indicated that their major concerns for the post-pandemic phase were experiencing longer waiting times to see a specialist (24.1%), suffering from social isolation and deteriorating mental well-being (23.1%), and facing delays in clinical trials with disinvestment in neuroscience research (13.1%).
Despite the great efforts of health services to cope with the first wave of the COVID-19 pandemic, individuals with neurological conditions feel they have been left behind. These findings provide invaluable insights for improving the care of patients with neurological disorders in the further course of the COVID-19 pandemic.
Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19—A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium
11 May 2021
Chou SH, Beghi E, Helbok R, et al. Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19—A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium. JAMA Netw Open. 2021;4(5):e2112131. doi:10.1001/jamanetworkopen.2021.12131
What are the incidence of and outcomes associated with neurologic manifestations in patients with COVID-19?
In this cohort study of 3744 patients in 2 large consortia, neurological manifestations were found in approximately 80% of patients hospitalized with COVID-19; the most common self-reported symptoms included headache (37%) and anosmia or ageusia (26%), whereas the most common neurological signs and/or syndromes were acute encephalopathy (49%), coma (17%), and stroke (6%). Presence of clinically captured neurologic signs and/or syndromes was associated with increased risk of in-hospital death.
These findings suggest that neurological manifestations are prevalent among patients hospitalized with COVID-19 and are associated with higher in-hospital mortality.
A plea for equitable global access to COVID‐19 diagnostics, vaccination and therapy: the NeuroCOVID‐19 task Force of the european Academy of neurology
18 January 2021
Coronavirus disease 2019 (COVID‐19), a multi‐organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurologic disease. COVID‐19 appears to have exposed inequalities of societies and healthcare systems and had disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID‐19. From the medical perspective, there is a need to consider inequalities in prevention, treatment, and long‐term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID‐19 Task Force intends to raise awareness of the potential impact of COVID‐19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational level.
Primary prevention of COVID‐19: Advocacy for vaccination from a neurological perspective
1 January 2021
Immunization by means of vaccination is a global health success story, saving millions of lives every year. In this regard, the epidemiology of measles, rabies, polio, rubella, varicella, influenza, and mumps infections, all of which can harm the nervous system, could be contained by global vaccination campaigns. In addition, toxoid vaccines against bacterial toxins such as tetanus and diphtheria are indispensable and effective interventions for toxin‐mediated neurologic diseases  The use of conjugate vaccines against major causes of bacterial meningitis (e.g., Haemophilus influenzae type b, Neisseria meningitidis, and Streptococcus pneumoniae) in routine pediatric immunization programs as well as for high‐risk groups have significantly lowered the burden of disease over the past three decades Immunization against measles is the only preventive measure against subacute sclerosing panencephalitis, a chronic progressive inflammatory disorder of the brain that is associated with a devastating course.
Prophylactic vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and the resulting coronavirus disease 2019 (COVID‐19) is an eagerly awaited measure to contain the pandemic, which has had devastating medical, economic, and social consequences.
The European Academy of Neurology COVID‐19 registry (ENERGY): an international instrument for surveillance of neurological complications in patients with COVID‐19
21 November 2020
The COVID‐19 pandemic is a global public health issue. Neurological complications have been reported in up to one‐third of affected cases, but their distribution varies significantly in terms of prevalence, incidence and phenotypical characteristics. Variability can be mostly explained by the differing sources of cases (hospital vs. community‐based), the accuracy of the diagnostic approach and the interpretation of the patients’ complaints. Moreover, after recovering, patients can still experience neurological symptoms. To obtain a more precise picture of the neurological manifestations and outcome of the COVID‐19 infection, an international registry (ENERGY) has been created by the European Academy of Neurology in collaboration with European national neurological societies and the Neurocritical Care Society and Research Network. ENERGY can be implemented as a stand‐alone instrument for patients with suspected or confirmed COVID‐19 and neurological findings or as an addendum to an existing registry not targeting neurological symptoms. Data are also collected to study the impact of neurological symptoms and neurological complications on outcomes. The variables included in the registry have been selected in the interests of most countries, to favour pooling with data from other sources and to facilitate data collection even in resource‐poor countries. Included are adults with suspected or confirmed COVID‐19 infection, ascertained through neurological consultation, and providing informed consent. Key demographic and clinical findings are collected at registration. Patients are followed up to 12 months in search of incident neurological manifestations. As of 19 August, 254 centres from 69 countries and four continents have made requests to join the study.
NeuroCOVID: it's time to join forces globally
Helbok, R., Chou, S.H.Y., Beghi, E., Mainali, S., Frontera, J., Robertson, C., Fink, E., Schober, M., Moro, E., McNett, M. and Bassetti, C.L., 2020. NeuroCOVID: it's time to join forces globally. The Lancet Neurology, 19(10), pp.805-806. Published:October, 2020 DOI:https://doi.org/10.1016/S1474-4422(20)30322-7
Since the recognition of the severe acute respiratory syndrome coronavirus 2 outbreak in December, 2019, there are now over 22·1 million COVID-19 cases worldwide, with more than 780 220 deaths. Reports of neurological manifestations associated with COVID-19 range from mild (headache, hyposmia, ageusia, myalgia, and fatigue or sleepiness) to severe (encephalopathy, ischemic and haemorrhagic strokes, seizures, hypoxic-ischaemic brain injury, and Guillain-Barré and other autoimmune syndromes), with prevalence rates ranging from 6% to 84%. The true prevalence, underlying mechanisms (infectious, autoimmune, secondary to systemic complications), and outcomes of COVID-19 neurological manifestations remain a key knowledge gap.
Many global initiatives have emerged to address these critical questions. The rapid and parallel implementation of these initiatives in a pandemic has resulted in discrepant data elements and definitions of neurological symptoms and signs. Furthermore, fragmented scientific approaches and overlapping consortia, in which centres can contribute data to multiple registries, raise the possibility of double-counting in future meta-analysis. All of these factors threaten the scientific rigour and yield of these combined global efforts. To address this issue, the European Academy of Neurology (EAN) and the Neurocritical Care Society (NCS)-endorsed Global Consortium Studies of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID) established a formal collaboration, thus forming the largest global network to date. An important research priority is to develop consensus and harmonisation of data elements with uniform definitions, which was emphasised in a recent Editorial in The Lancet Neurology.
EAN consensus statement for management of patients with neurological diseases during the COVID‐19 pandemic
15 October 2020
Background and purpose
The recent SARS‐CoV‐2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast‐evolving pandemic, evidence‐based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID‐19.
A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co‐chairs rated importance on a five‐point Likert scale. Results were graded by importance and reported as consensus statements.
In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty‐nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co‐chairs of 29 SPs. Whilst general recommendations related to prevention of COVID‐19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy.
This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID‐19 pandemic that provides immediate guidance for neurologists. In this fast‐evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges.
Tim von Oertzen
The international European Academy of Neurology survey on neurological symptoms in patients with COVID‐19 infection
17 June 2020
Background and purpose
Although the main clinical features of COVID‐19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. The incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID‐19 Task Force initiated a survey on neurological symptoms observed in patients with COVID‐19 infection.
A 17‐question online survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on 9 April 2020.
By 27 April 2020, proper data were collected from 2343 responders (out of 4199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID‐19 mainly in emergency rooms and in COVID‐19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID‐19 (neuro COVID‐19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%) and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID‐19; they were most commonly recognized in patients with multiple general symptoms and occurred at any time during infection.
Neurologists are currently and actively involved in the management of neurological issues related to the COVID‐19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID‐19, neurological disease characteristics and the contribution of neurological manifestations to outcome.