Serious neurological adverse events following immunization against SARS-CoV-2: a narrative review of the literature.

Amid the coronavirus disease 2019 (COVID-19) pandemic, massive immunization campaigns became the most promising public health measure. During clinical trials, certain neurological adverse effects following immunization (AEFIs) were observed; however, acceptable safety profiles lead to emergency authorization for the distribution and use of the vaccines. To contribute to pharmacovigilance and lessen the potential negative impact that vaccine hesitancy would have on immunization programs, we conducted a review of the scientific literature concerning the epidemiological data, clinical presentation, and potential mechanisms of these neurological AEFIs. There is some epidemiological evidence linking COVID-19 vaccines to cerebral venous sinus thrombosis, arterial ischemic stroke, convulsive disorder, Guillain-Barré syndrome, facial nerve palsy, and other neurological conditions. Cerebral venous sinus thrombosis has been associated with a thrombotic thrombocytopenia induced by the vaccine, similar to that induced by heparin, which suggests similar pathogenic mechanisms (likely involving antibodies against platelet factor 4, a chemokine released from activated platelets). Arterial ischemic stroke is another thrombotic condition observed among some COVID-19 vaccine recipients. Vaccine-induced convulsive disorder might be the result of structural abnormalities potentially caused by the vaccine or autoimmune mechanisms. Guillain-Barré syndrome and facial nerve palsy may also be linked to the immunization event, possibly due to immune mechanisms such as uncontrolled cytokine release, autoantibody production, or bystander effect. However, these events are mostly uncommon and the evidence for the association with the vaccine is not conclusive. Furthermore, the potential pathophysiological mechanisms remain largely unknown. Nevertheless, neurological AEFIs can be serious, life-threatening or even fatal. In sum, COVID-19 vaccines are generally safe and the risk of neurological AEFIs does not outweigh the benefits of immunization. However, early diagnosis and treatment of neurological AEFIs are of utmost importance, and both health professionals and the public should be aware of these conditions.

A review of undesired effects involving the nervous system following the administration of COVID-19 vaccines Among the range of complications that can occur after a vaccine, some of them can affect the nervous system and its vasculature. This narrative review aims to evaluate some serious neurological conditions following COVID-19 vaccination. We searched biomedical journal databases where physicians around the globe reported different complications after the administration of different COVID-19 vaccines. Besides reports of cases in individual patients or small groups, we reviewed studies that included bigger groups of patients (e.g. vaccinated versus non-vaccinated) and compared the occurrence of these events between them. We found that after the administration of a certain type of vaccine (e.g. ChAdOx1-S/Oxford, AstraZeneca vaccine), serious neurological complications were rare, with abnormal clot formation involving cerebral blood vessels being one of the most important among them. Nonetheless, other conditions have been observed after the administration of the vaccines; however, it is not certain yet if the vaccines are the actual cause of these complications. There are some hypotheses that could explain why these adverse reactions take place after a vaccine. For instance, an abnormal immune response to the vaccine leads to the production of antibodies (i.e. proteins made by the immune system in response to the presence of a foreign substance). These antibodies trigger a response that could eventually result in clot formation. Besides, the immune response can also produce other adverse effects, including convulsive disorder, Guillain­Barré syndrome, and facial nerve palsy. Scientific evidence suggests that vaccines are safe overall. While mild complications, such as pain at the site of injection or bruising might occur, more serious events remain rare. Furthermore, the complications derived from COVID-19 are far more likely in non-vaccinated individuals than the complications associated with the vaccine. Thus, vaccination continues to be the safest and most effective strategy to control the ongoing pandemic. However, both health professionals and the public should be aware of the possibility of serious neurological adverse reactions occurring after vaccination to allow early diagnosis and treatment.

Review of Neurological Manifestations of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect any part of the neuraxis. Many neurological conditions have been attributed to be caused by SARS-CoV-2, namely encephalopathy (acute necrotizing encephalopathy and encephalopathy with reversible splenial lesions), seizures, stroke, cranial nerve palsies, meningoencephalitis, acute disseminated encephalomyelitis (ADEM), transverse myelitis (long and short segment), Guillain-Barré syndrome (GBS) and its variants, polyneuritis cranialis, optic neuritis (ON), plexopathy, myasthenia gravis (MG), and myositis. The pathophysiology differs depending on the time frame of presentation. In patients with concomitant pulmonary disease, for instance, acute neurological illness appears to be caused by endotheliopathy and cytokine storm. Autoimmunity and molecular mimicry are causative for post-coronavirus disease 2019 (COVID-19)-sequelae. It has not yet been shown that the virus can penetrate the central nervous system (CNS) directly. This review aims to describe the disease and root pathogenic cause of the various neurological manifestations of COVID-19. We searched Pubmed/Medline and Google Scholar using the keywords "SARS-CoV-2" and "neurological illness" for articles published between January 2020 and November 2022. Then, we used the SWIFT-Review (Sciome LLC, North Carolina, United States), a text-mining workbench for systematic review, to classify the 1383 articles into MeSH hierarchical tree codes for articles on various parts of the nervous system, such as the CNS, peripheral nervous system, autonomic nervous system, neuromuscular junction, sensory system, and musculoskeletal system. Finally, we reviewed 152 articles in full text. SARS-CoV-2 RNA has been found in multiple brain areas without any histopathological changes. Despite the absence of in vivo virions or virus-infected cells, CNS inflammation has been reported, especially in the olfactory bulb and brain stem. SARS-CoV-2 genomes and proteins have been found in affected individuals' brain tissues, but corresponding neuropathologic changes are seldom found in these cases. Additionally, viral RNA can rarely be identified in neurological patients' CSF post hoc SARS-CoV-2 infection. Most patients with neurological symptoms do not have active viral replication in the nervous system and infrequently have typical clinical and laboratory characteristics of viral CNS infections. Endotheliopathy and the systemic inflammatory response to SARS-CoV-2 infection play a crucial role in developing neuro-COVID-19, with proinflammatory cytokine release mediating both pathological pathways. The systemic inflammatory mediators likely activate astrocytes and microglia across the blood-brain barrier, indirectly affecting CNS-specific immune activation and tissue injury. The management differs according to co-morbidities and the neurological disorder.

Seronegative acute encephalitis following COVID-19 vaccines: a case series of an overlooked diagnosis with literature review.

PURPOSE: Autoimmune encephalitis is a neurological emergency of new-onset altered mental status, caused by an exaggerated immune-mediated response that targets the central nervous system. Autoimmune encephalitis has become an emerging differential diagnosis, when a classical infection cannot explain neurological symptoms. Displaying overlapping clinical presentations, ranging from the insidious onset of cognitive deficiency to more severe forms of encephalopathy with refractory seizures, autoimmune encephalitis can be challenging for clinicians. When evidence of malignancy is absent and pathogenic autoantibodies are undetected, with typical clinical and imaging features of autoimmune encephalitis, seronegative autoimmune encephalitis may be considered. Recently, vaccination-related autoimmune encephalitis and acute encephalitis after COVID-19 vaccination have attracted attention. METHODS AND RESULTS: We report a case series consisting of three patients with autoimmune encephalitis occurring shortly after COVID-19 vaccination and a current review of all previous reported autoimmune encephalitis related to COVID-19 vaccines. CONCLUSION: We emphasise on the prompt diagnosis of autoimmune encephalitis induced by Covid-19 vaccines and its timely treatment to improve the clinical outcome of this severe neurological condition. Post-licencing vaccine safety surveillance for potential adverse events is essential for vaccine safety and public confidence.

[Dermato-neuro syndrome-an acute and life-threatening complication of scleromyxedema Arndt-Gottron]. / Dermato-neurologisches Syndrom ­ eine akute und lebensbedrohliche Komplikation des Skleromyxödems Arndt-Gottron.

Scleromyxedema Arndt-Gottron is the systemic variant of lichen myxedematosus in which mucin accumulation occurs in the dermis. The disease is usually chronically progressive and extracutaneous manifestations or complications are possible. The pathogenesis is unknown and the disease is usually associated with monoclonal gammopathy. High-dose intravenous immunoglobulins (IVIg) are considered to be an effective therapy. We report the case of a patient who developed dermato-neuro syndrome following an interruption of IVIg treatment and a SARS-CoV­2 infection. A similar episode occurred 2 years earlier in association with an influenza A infection. Dermato-neuro syndrome is a potentially lethal neurological complication which is characterized by fever, delirium, convulsions, and coma.

Impact of new-onset and preexisting neurological disorders in COVID-19 patients.

BACKGROUND AND PURPOSE: Coronavirus disease (COVID-19) is still considered a global pandemic. The prognosis of COVID-19 patients varies greatly. We aimed to assess the impact of preexisting, chronic neurological diseases (CNDs) and new-onset acute neurological complications (ANCs) on the disease course, its complications, and outcomes. METHODS: We conducted a monocentric retrospective analysis from all hospitalized COVID-19 patients between May 1, 2020 and January 31, 2021. Employing multivariable logistic regression models, we explored the association of CNDs and ANCs separately with hospital mortality and functional outcome. RESULTS: A total of 250 among 709 patients with COVID-19 had CNDs. We found a 2.0 times higher chance of death (95% confidence interval [CI]: 1.37-2.92) for CND patients than for non-CND patients. The chance for an unfavorable functional outcome (modified Rankin Scale > 3 at discharge) was 1.67 times higher in patients with CNDs than those without (95% CI: 1.07-2.59). Furthermore, 117 of all patients had 135 ANCs in total. We observed a 1.86 times higher chance to die (95% CI: 1.18-2.93) for patients with ANCs than without. The chance for a worse functional outcome was 3.6-fold higher in ANC patients than without (95% CI: 2.22-6.01). Patients with CNDs had 1.73 times higher odds for developing ANCs (95% CI: 0.97-3.08). CONCLUSION: Preexisting neurologic disorders or ANCs in COVID-19 patients were associated with higher mortality and poorer functional outcome at discharge. Furthermore, development of acute neurologic complications was more frequent in patients with preexisting neurologic disease. Early neurological evaluation appears to be an important prognostic factor in COVID-19 patients.

Uncovering a neurological protein signature for severe COVID-19.

Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has sparked a global pandemic with severe complications and high morbidity rate. Neurological symptoms in COVID-19 patients, and neurological sequelae post COVID-19 recovery have been extensively reported. Yet, neurological molecular signature and signaling pathways that are affected in the central nervous system (CNS) of COVID-19 severe patients remain still unknown and need to be identified. Plasma samples from 49 severe COVID-19 patients, 50 mild COVID-19 patients, and 40 healthy controls were subjected to Olink proteomics analysis of 184 CNS-enriched proteins. By using a multi-approach bioinformatics analysis, we identified a 34-neurological protein signature for COVID-19 severity and unveiled dysregulated neurological pathways in severe cases. Here, we identified a new neurological protein signature for severe COVID-19 that was validated in different independent cohorts using blood and postmortem brain samples and shown to correlate with neurological diseases and pharmacological drugs. This protein signature could potentially aid the development of prognostic and diagnostic tools for neurological complications in post-COVID-19 convalescent patients with long term neurological sequelae.

Neurological diseases caused by coronavirus infection of the respiratory airways

Infections of the central nervous system (CNS) infections are critical problems for public health. They are caused by several different organisms, including the respiratory coronaviruses (CoVs). CoVs usually infect the upper respiratory tract causing the common cold. However, in infants, and in elderly and immunocompromised persons, they can also affect the lower respiratory tract causing pneumonia and various syndromes of respiratory distress. CoVs also have neuroinvasive capabilities because they can spread from the respiratory tract to the CNS. Once infection begins in the CNS cells, it can cause various CNS problems such as status epilepticus, encephalitis, and long‐term neurological disease. This neuroinvasive properties of CoVs may damage the CNS as a result of misdirected host immune response, which could be associated with autoimmunity in susceptible individuals (virus‐induced neuro‐immunopathology) or associated with viral replication directly causing damage to the CNS cells (virus‐induced neuropathology). In December 2019, a new disease named COVID‐19 emerged which is caused by CoVs. The significant clinical symptoms of COVID‐19 are related to the respiratory system, but they can also affect the CNS, causing acute cerebrovascular and intracranial infections. We describe the possible invasion routes of coronavirus in this review article, and look for the most recent findings associated with the neurological complications in the recently published literature.

Meningoencephalitis Associated with SARS-Coronavirus-2.

The aim of this work is to clarify the incidence of meningitis/encephalitis in SARS-CoV-2 patients. We conducted an initial search in PubMed using the Medical Subject Headings (MeSH) terms "meningitis," and "encephalitis,", and "COVID-19" to affirm the need for a review on the topic of the relationship between meningitis/encephalitis and SARS-CoV-2 infection. We included case series, case reports and review articles of COVID-19 patients with these neurological symptoms. Through PubMed database we identified 110 records. After removal of duplicates, we screened 70 record, and 43 were excluded because they focused on different SARS-CoV-2 neurological complications. For eligibility, we assessed 27 full-text articles which met inclusion criteria. Seven articles were excluded, and twenty studies were included in the narrative review, in which encephalitis and/or meningitis case reports/case series were reported. Neurological manifestations of COVID-19 are not rare, especially meningoencephalitis; the hypoxic/metabolic changes produced by the inflammatory response against the virus cytokine storm can lead to encephalopathy, and the presence of comorbidities and other neurological diseases, such as Alzheimer's disease, predispose to these metabolic changes. Further study are needed to investigate the biological mechanisms of neurological complications of COVID-19.

A Systematic Review of Neurological Complications in Pregnant Women With COVID-19.

Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has killed millions of people around the world so far and has turned into a disaster for people and healthcare systems. Neurological problems are often seen in people with COVID-19 in the general population, but it is unclear how common they are in pregnant women. This study provides a summary of studies on pregnant women with proven SARS-CoV-2 infection and a particular neurologic diagnosis from different parts of the world. After applying the inclusion and exclusion criteria, a total of 15 papers were assessed to create this review article. Based on our findings, the peripheral and central nervous systems were both equally impacted: Guillain-Barré syndrome (GBS, n=1), bifacial weakness, paresthesia, and vestibulocochlear neuritis (n=1), eclampsia types (n=2), and neurological disease (n=2); case reports, retrospective studies, editorials, and prospective observational studies were included. The median gestational age was 34 (30-36.5) weeks, and the median maternal age was 32.5 (25-35) years. Given the number of reports of neurologic problems associated with COVID-19 in the general community, our findings might be overstated, and we chose the ones that fit our criteria. We hope that this review helps in the early detection and management of neurological diseases during pregnancy.

Systemic and Cerebral Effects of Physiotherapy in Mechanically Ventilated Subjects.

BACKGROUND: Physiotherapy may result in better functional outcomes, shorter duration of delirium, and more ventilator-free days. The effects of physiotherapy on different subpopulations of mechanically ventilated patients on respiratory and cerebral function are still unclear. We evaluated the effect of physiotherapy on systemic gas exchange and hemodynamics as well as on cerebral oxygenation and hemodynamics in mechanically ventilated subjects with and without COVID-19 pneumonia. METHODS: This was an observational study in critically ill subjects with and without COVID-19 who underwent protocolized physiotherapy (including respiratory and rehabilitation physiotherapy) and neuromonitoring of cerebral oxygenation and hemodynamics. PaO2 /FIO2 , PaCO2 , hemodynamics (mean arterial pressure [MAP], mm Hg; heart rate, beats/min), and cerebral physiologic parameters (noninvasive intracranial pressure, cerebral perfusion pressure using transcranial Doppler, and cerebral oxygenation using near-infrared spectroscopy) were assessed before (T0) and immediately after physiotherapy (T1). RESULTS: Thirty-one subjects were included (16 with COVID-19 and 15 without COVID-19). Physiotherapy improved PaO2 /FIO2 in the overall population (T1 = 185 [108-259] mm Hg vs T0 = 160 [97-231] mm Hg, P = .02) and in the subjects with COVID-19 (T1 = 119 [89-161] mm Hg vs T0 = 110 [81-154] mm Hg, P = .02) and decreased the PaCO2 in the COVID-19 group only (T1 = 40 [38-44] mm Hg vs T0 = 43 [38-47] mm Hg, P = .03). Physiotherapy did not affect cerebral hemodynamics, whereas increased the arterial oxygen part of hemoglobin both in the overall population (T1 = 3.1% [-1.3 to 4.9] vs T0 = 1.1% [-1.8 to 2.6], P = .007) and in the non-COVID-19 group (T1 = 3.7% [0.5-6.3] vs T0 = 0% [-2.2 to 2.8], P = .02). Heart rate was higher after physiotherapy in the overall population (T1 = 87 [75-96] beats/min vs T0 = 78 [72-92] beats/min, P = .044) and in the COVID-19 group (T1 = 87 [81-98] beats/min vs T0 = 77 [72-91] beats/min, P = .01), whereas MAP increased in the COVID-19 group only (T1 = 87 [82-83] vs T0 = 83 [76-89], P = .030). CONCLUSIONS: Protocolized physiotherapy improved gas exchange in subjects with COVID-19, whereas it improved cerebral oxygenation in non-COVID-19 subjects.

Neurological Complications of COVID-19 in the Elderly.

SARS-CoV-2 virus is a ß-coronavirus and produces a severe viral pneumonia which can be complicated by acute respiratory distress syndrome and multiorgan failure. As knowledge of the new coronavirus infection (COVID-19) increases, it has become known that SARS-CoV-2 has pronounced neurotropism, producing a wide spectrum of neurological complications. This article addresses the characteristics of the neurological complications of COVID-19 in elderly people.

Neurological consequences of COVID-19.

In December 2019, cases of pneumonia caused by infection with the previously unknown severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to coronavirus disease 2019 (COVID-19), were identified. Typical manifestations of COVID-19 are fever, cough, fatigue and dyspnoea. Initially, it was thought that the mechanism of action of SARS-CoV-2 was only associated with respiratory tract invasion, but it was later revealed that the infection might involve many other organs and systems, including the central and peripheral nervous systems. Neurological complications associated with SARS-CoV-2 infection include encephalopathy, encephalitis, meningitis, acute disseminated encephalomyelitis (ADEM), ischaemic and haemorrhagic stroke and cerebral venous sinus thrombosis. In cases of peripheral nervous system involvement, smell and taste disorders, myopathy or the signs and symptoms of Guillain‒Barré syndrome are observed. The most common early neurological complications, particularly during the first year of the epidemic, were anosmia and taste disorders, which, according to some studies, occurred in over 80 percent of patients with COVID-19. The proportion of patients with serious neurological manifestations was small compared to the global number of patients, but the numbers of SARS-CoV-2 infections and critical patients increased substantially. The experience from 2 years of the pandemic has shown that approximately 13% of infected patients suffer from severe neurological complications. The relationship between SARS-CoV-2 and the nervous system is not only a cause of neurological complications in previously healthy individuals but also directly and indirectly affects the courses of many nervous system diseases.

Case report: A case of acute disseminated encephalomyelitis after SARS-CoV-2 infection in pediatric patients.

Introduction: Since the beginning, there has been enough evidence about the multi-systematic involvement of the coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent observations have revealed that, together with others, typical neurological manifestations are also associated with COVID-19 infection. In the first 2 years, children accounted for a few percent of cases, but with the emergence of the Omicron variant, the number of cases in the pediatric population has increased. It has been described that ~5% of the affected population suffered from severe neurological complications, such as seizure, coma, encephalitis, demyelinating disorders, and aseptic meningitis. Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system. Typically, it presents in childhood and occurs 1 or 2 weeks after infection or vaccination. Case presentation: We present the case of a 12-year-old boy who developed ADEM, 10 days after an asymptomatic SARS-CoV-2 infection. Neurological symptoms began with headache, fever, irritability, paraplegia, and loss of sensitivity from the T1 level. The diagnosis of ADEM was confirmed by the typical signs found on brain MRI, whereas spinal cord MRI showed signs of transverse myelitis. The cerebrospinal fluid (CSF) testing excluded infections and did not reveal oligoclonal antibody bands (anti-MOG-negative and anti-AQP-negative). High-dose steroids (30 mg/kg/day) and IVIG (2 g/kg) were administered to the patient without any clinical improvement. The patient received a cycle of plasma exchange therapy, followed by rituximab infusion, with partial improvement. After 3 months, the magnetic resonance imaging (MRI) results demonstrated radiological improvement in accordance with the ADEM diagnosis. Conclusion: This clinical case confirms that SARS-CoV-2 infections are increasingly implicated in severe neurological consequences in both adult and pediatric patients. While the most frequent complications that were reported in children included headache, altered mental status, and encephalopathy, ~5% of the individuals suffered from severe neurological complications, leading to lifelong sequelae. All physicians must be aware of these data and detect neurological signs of severe (or not) complications that require a specific follow-up and treatment.

Neurological Consequences of Pulmonary Emboli in COVID-19 Patients: A Study of Incidence and Outcomes in the Kingdom of Saudi Arabia.

Pulmonary embolism (PE) is a significant consequence that is becoming more common in COVID-19 patients. The current study sought to determine the prevalence and risk factors for PE in a study population of COVID-19 patients, as well as the relationship between PE and neurological sequelae. The research also sought to analyze the consistency of neurological examination and imaging techniques in detecting neurological problems. The research comprised a total of 63 individuals with COVID-19. The incidence of PE in the study group was 9.5% for smokers, 23.8% for obese patients, 33.3% for hypertensive patients, and 19% for diabetic patients, according to the findings. After adjusting for possible confounders such as age, gender, BMI, smoking, hypertension, and diabetes, a logistic regression analysis indicated that the probabilities of having neurological complications were 3.5 times greater in individuals who had PE. In conclusion, the present study highlights the high incidence of PE among patients with COVID-19 and the association between PE and neurological complications. The study also emphasizes the importance of a thorough neurological examination and imaging studies in the detection of neurological complications in patients with PE.

Investigation of Neurological Complications after COVID-19 Vaccination: Report of the Clinical Scenarios and Review of the Literature.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in 2019 and became a pandemic in 2020. Since then, vaccines have been approved to prevent severe illness. However, vaccines are associated with the risk of neurological complications ranging from mild to severe. Severe complications such as vaccine-induced immune thrombotic thrombocytopenia (VITT) associated with acute ischaemic stroke have been reported as rare complications post-COVID-19 vaccination. During the pandemic era, VITT evaluation is needed in cases with a history of vaccination within the last month prior to the event. Cerebral venous sinus thrombosis (CVST) should be suspected in patients following immunization with persistent headaches who are unresponsive to analgesics. In this article, we investigated neurological complications after COVID-19 vaccination and provided more subsequent related clinical studies of accurate diagnosis, pathophysiological mechanisms, incidence, outcome, and management.

Neurological Complications Following COVID-19 Vaccination.

PURPOSE OF REVIEW: A variety of neurological complications have been reported following the widespread use of the COVID-19 vaccines which may lead to vaccine hesitancy and serve as a major barrier to the public health aim of achieving protective herd immunity by vaccination. In this article, we review the available evidence regarding these neurological adverse events reported, to provide clarity regarding the same so that unfounded fears maybe put to rest. RECENT FINDINGS: There is a greater than expected occurrence of severe neurological adverse events such as cortical sinus venous thrombosis, Bell's palsy, transverse myelitis, and Guillain-Barré syndromes along with other common effects such as headaches following different kinds of COVID-19 vaccination. Precipitation of new onset demyelinating brain lesions with or without detection of specific antibodies and worsening of pre-existing neurological disorders (like epilepsy, multiple sclerosis) are also a matter of great concern though no conclusive evidence implicating the vaccines is available as of now. The COVID-19 pandemic is far from being over. Till such time that a truly effective anti-viral drug is discovered, or an appropriate therapeutic strategy is developed, COVID-appropriate behavior and highly effective mass vaccination remain the only weapons in our armamentarium to fight this deadly disease. As often occurs with most therapeutic means for the treatment and prevention of any disease, vaccination against COVID-19 has its hazards. These range from the most trivial ones like fever, local pain and myalgias to several potentially serious cardiac and neurological complications. The latter group includes conditions like cerebral venous thrombosis (curiously often with thrombocytopenia), transverse myelitis and acute inflammatory demyelinating polyneuropathy amongst others. Fortunately, the number of reported patients with any of these serious complications is far too low for the total number of people vaccinated. Hence, the current evidence suggests that the benefits of vaccination far outweigh the risk of these events in majority of the patients. As of now, available evidence also does not recommend withholding vaccination in patients with pre-existing neurological disorders like epilepsy and MS, though adenoviral vaccines should be avoided in those with history of thrombotic events.

Comparative features and outcomes of major neurological complications of COVID-19.

BACKGROUND AND PURPOSE: The aim of this study was to assess the neurological complications of SARS-CoV-2 infection and compare phenotypes and outcomes in infected patients with and without selected neurological manifestations. METHODS: 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 complications, 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. RESULTS: By July 31, 2021, 1523 patients (758 men, 756 women, and nine intersex/unknown, 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 manifestations, extent of association with other acute/subacute neurological manifestations, and outcome. CONCLUSIONS: Patients with COVID-19 and neurological manifestations present with distinct phenotypes. Differences in age, general and neurological comorbidities, and infection severity characterize the various neurological manifestations of COVID-19.

European Working Group on SARS-CoV-2: Current Understanding, Unknowns, and Recommendations on the Neurological Complications of COVID-19.

Background: The emergence of COVID-19 was rapidly followed by infection and the deaths of millions of people across the globe. With much of the research and scientific advancement rightly focused on reducing the burden of severe and critical acute COVID-19 infection, the long-term effects endured by those who survived the acute infection has been previously overlooked. Now, an appreciation for the post-COVID-19 condition, including its neurological manifestations, is growing, although there remain many unknowns regarding the etiology and risk factors of the condition, as well as how to effectively diagnose and treat it. Methods: Here, drawing upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, we have reviewed the current literature to provide a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Results: In this review, we provide a summary of the neurological symptoms associated with the post-COVID-19 condition, before discussing the possible mechanisms which may underly and manifest these symptoms. Following this, we explore the risk factors for developing neurological symptoms as a result of COVID-19 and the post-COVID-19 condition, as well as how COVID-19 infection may itself be a risk factor for the development of neurological disease in the future. Lastly, we evaluate how the post-COVID condition could be accurately diagnosed and effectively treated, including examples of the current guidelines, clinical outcomes, and tools that have been developed to aid in this process, as well as addressing the protection provided by COVID-19 vaccines against the post-COVID-19 condition. Conclusions: Overall, this review provides a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Impact statement With our understanding of the neurological complications of the post-COVID-19 condition currently lacking sufficient depth, this review aimed at highlighting the current knowns and unknowns of the post-COVID-19 condition. In this review, we draw upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, as well as explore the current published literature, to evaluate a range of topics associated with the neurological complications of the post-COVID-19 condition. As a result, we have provided a comprehensive review of the topic. The European Working Group on SARS-CoV-2 Many essential questions surrounding COVID-19 remain unanswered, including its neurological complications and associated sequalae. In this review, we aim at identifying the current gaps in our understanding of post-COVID-19 neurological sequalae and suggest how future studies should be undertaken to fill these gaps. This review will draw upon the current biological and mechanistic understanding of COVID-19 and post-COVID-19 complications to discuss the clinically relevant aspects associated with the neurological manifestations of post-COVID-19 syndrome. From our discussions, the following questions were considered highly relevant for contemplation.