Neurological or Psychiatric Disorders After Dengue Fever.

This cohort study investigates the association between dengue fever and risk of neurological and psychiatric disorders among adults in Taiwan.

Unlocking the potential of adeno-associated virus in neuroscience: a brief review.

Adeno-associated virus (AAV) has emerged as a pivotal tool in neuroscience research, owing to its remarkable versatility and efficiency in delivering genetic material to diverse cell types within the nervous system. This mini review aims to underscore the advanced applications of AAV vectors in neuroscience and their profound potential to revolutionize our understanding of brain function and therapeutic interventions for neurological disorders. By providing a concise overview of the latest developments and strategies employing AAV vectors, this review illuminates the transformative role of AAV technology in unraveling the complexities of neural circuits and paving the way for innovative treatments. Through elucidating the multifaceted capabilities of AAV-mediated gene delivery, this review underscores its pivotal role as a cornerstone in contemporary neuroscience research, promising remarkable insights into the intricacies of brain biology and offering new avenues for therapeutic intervention.

Serious neurological adverse events in immunocompetent children and adolescents caused by viral reactivation in the years following varicella vaccination.

Serious adverse events following vaccination include medical complications that require hospitalisation. The live varicella vaccine that was approved by the Food and Drug Administration in the United States in 1995 has an excellent safety record. Since the vaccine is a live virus, adverse events are more common in immunocompromised children who are vaccinated inadvertently. This review includes only serious adverse events in children considered to be immunocompetent. The serious adverse event called varicella vaccine meningitis was first reported in a hospitalised immunocompetent child in 2008. When we carried out a literature search, we found 15 cases of immunocompetent children and adolescents with varicella vaccine meningitis; the median age was 11 years. Eight of the children had received two varicella vaccinations. Most of the children also had a concomitant herpes zoster rash, although three did not. The children lived in the United States, Greece, Germany, Switzerland, and Japan. During our literature search, we found five additional cases of serious neurological events in immunocompetent children; these included 4 cases of progressive herpes zoster and one case of acute retinitis. Pulses of enteral corticosteroids as well as a lack of herpes simplex virus antibody may be risk factors for reactivation in immunocompetent children. All 20 children with adverse events were treated with acyclovir and recovered; 19 were hospitalised and one child was managed as an outpatient. Even though the number of neurological adverse events remains exceedingly low following varicella vaccination, we recommend documentation of those caused by the vaccine virus.

A Systematic Review Unraveling the Intricate Neurological Spectrum of COVID-19: Manifestations, Complications, and Transformative Insights for Patient Care.

The coronavirus disease 2019 (COVID-19) pandemic has strained global healthcare and financial infrastructures. Neurological manifestations of COVID-19 have gained recognition, emphasizing the need for comprehensive research in this area. This systematic review aims to comprehensively examine the neurological manifestations and complications associated with COVID-19 and assess their prevalence, impact on patient outcomes, and potential relationships with comorbidities, while emphasizing the significance of ongoing research in this field. We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guidelines. A comprehensive search of PubMed, Google Scholar, Science Direct, and ResearchGate databases was conducted to identify eligible studies focusing on COVID-19 patients, reporting neurological symptoms or complications, and published between 2020 and 2022 in English. The data extracted is performed in a Microsoft Excel spreadsheet. Two independent reviewers assessed study quality and bias using the AMSTAR 2 scale before inclusion. This systematic includes 12 systematic reviews and meta-analysis with 191,412 participants and average age of 60 years. Neurological symptoms included headaches, dizziness, anosmia, and ageusia. Complications ranged from cerebrovascular events to Guillain-Barré syndrome. Comorbidities, such as hypertension and diabetes, exacerbated severity. Mortality rates associated with neurological manifestations varied from 29.1% to 84.8%. The study underscores the complex neurological impact of COVID-19, affecting patients across age groups. Ongoing research is vital to understand mechanisms and develop targeted interventions, improving patient care and addressing pandemic consequences. This review provides a holistic view of COVID-19's neurological effects, emphasizing the need for sustained research efforts and collaborative endeavors to combat the neurological issues.

Neurological manifestations and risk factors associated with poor prognosis in hospitalized children with Omicron variant infection.

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.

Rehabilitación diaria de personas con secuela neurológica post-covid-19: scoping review / Rehabilitation in the day-to-day of people with post-covid-19 neurological sequelae: scoping review

Objetivo: Mapear las evidencias científicas disponibles sobre rehabilitación en el cotidiano de personas con secuela neurológica post covid-19. Metodología: Se trata de una scoping review según las directrices del Joanna Briggs Institute. Los estudios incluidos se basaron en la estrategia mnemónica participants/ problem (personas adultas con secuela neurológica), concept (rehabilitación en lo cotidiano) y context (pandemia covid-19), con espacio temporal de 2020 a 2022, disponibles en las siete bases de datos seleccionadas, en los idiomas portugués, inglés y español, recogidos y analizados según PRISMA-ScR. Resultados: Fueron recuperados 1.027 estudios, siendo que la muestra fue compuesta por 11 artículos que presentaron programas de rehabilitación para las secuelas: fatiga, anosmia, trastornos cognitivos y neuropsicológicos. Entre los principales programas de rehabilitación encontrados, destacan: caminata de progresión, ejercicios respiratorios; entrenamiento olfativo usando aceites esenciales y abordajes cognitivos. A partir de los hallazgos, el proceso de rehabilitación ha demostrado ser eficaz para el manejo de las secuelas neurológicas post-covid-19, debiendo ser iniciado precozmente. Conclusiones: Se recomienda que los programas de rehabilitación cuenten con la participación de un equipo multiprofesional, ya que la enfermedad presenta síntomas persistentes multisistémicos, que implican un enfoque holístico y abarcan aspectos de comportamiento relacionados con el autocuidado, rehabilitación física, apoyo emocional y educación en salud, promoviendo la recuperación y mejora de la calidad de vida de los individuos afectados por la enfermedad (AU)

Objetivo: Mapear as evidências científicas disponíveis sobre reabilitação no quotidiano de pessoas com sequela neurológica pós-COVID-19. Metodologia: Trata-se de uma scoping review segundo as diretrizes do Joanna Briggs Institute. Os estudos incluídos basearam-se na estratégia mnemônica participants/ problem (pessoas adultas com sequela neurológica), concept (reabilitação no quotidiano) e context (pandemia covid-19), com espaço temporal de 2020 a 2022, disponíveis nas sete bases de dados selecionadas, nos idiomas português, inglês e espanhol, coletados e analisados segundo o PRISMA-ScR. Resultados: Foram recuperados 1.027 estudos, sendo que a amostra foi composta por 11 artigos que apresentaram programas de reabilitação para as sequelas: fadiga, anosmia, distúrbios cognitivos e neuropsicológicos. Dentre os principais programas de reabilitação encontrados, destacam-se: caminhada de progressão, exercícios respiratórios; treinamento olfativo usando óleos essenciais e abordagens cognitivas. A partir dos achados, o processo de reabilitação tem se mostrado eficaz para o manejo das sequelas neurológicas pós-covid-19, devendo ser iniciado precocemente. Conclusões: Recomenda-se que os programas de reabilitação envolvam uma equipe multiprofissional, já que a doença apresenta sintomas persistentes multissistêmicos, envolvendo uma abordagem holística, que englobe aspectos comportamentais relacionados ao autocuidado, reabilitação física, suporte emocional e educação em saúde, promovendo a recuperação e melhora da qualidade de vida dos indivíduos afetados pela doença (AU)

Objective: To map available scientific evidence on rehabilitation in the daily lives of people with post-covid-19 neurological sequelae. Methodology: This is a scoping review according to the guidelines of the Joanna Briggs Institute. The included studies were based on the mnemonic strategy participants/ problem (adult people with neurological sequelae), concept (rehabilitation in everyday life) and context (covid-19 pandemic), with timeframe from 2020 to 2022, available in the seven selected databases, in Portuguese, English and Spanish, collected and analyzed according to PRISMA-ScR. Results: A total of 1,027 studies were recovered, and the sample consisted of 11 articles that presented rehabilitation programs for sequelae: fatigue, anosmia, cognitive and neuropsychological disorders. Among the main rehabilitation programs found, the following stand out: progression walking, breathing exercises; olfactory training using essential oils and cognitive approaches. From the findings, the rehabilitation process has been shown to be effective for the management of post-covid-19 neurological sequelae, and should be started early. Conclusions: Rehabilitation programs should involve a multidisciplinary team, since the disease presents persistent multisystemic symptoms, involving a holistic approach, which encompasses behavioral aspects related to self-care, physical rehabilitation, emotional support and health education, promoting recovery and improving the quality of life of individuals affected by the diseas (AU)

Sirtuin-2, NAD-Dependent Deacetylase, Is a New Potential Therapeutic Target for HIV-1 Infection and HIV-Related Neurological Dysfunction.

The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (n = 9) or delayed initiation (n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure. IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD+ deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction.

COMPARATIVE EVALUATION AND PROGNOSTIC UTILITY OF NEURONAL INJURY BIOMARKERS IN COVID-19 PATIENTS: A PROSPECTIVE STUDY.

ABSTRACT: Background : COVID-19 disease severity markers include mostly molecules related to not only tissue perfusion, inflammation, and thrombosis, but also biomarkers of neural injury. Clinical and basic research has demonstrated that SARS-COV-2 affects the central nervous system. The aims of the present study were to investigate the role of neural injury biomarkers and to compare them with inflammatory markers in their predictive ability of mortality. Methods : We conducted a prospective observational study in critically ill patients with COVID-19 and in a cohort of patients with moderate/severe disease. S100b, neuron-specific enolase (NSE), and inflammatory markers, including soluble urokinase plasminogen activator receptor (suPAR), were measured on intensive care unit or ward admission, respectively. Statistical comparisons between patient groups were performed for all biomarkers under investigation. Correlations between different biomarkers were tested with Spearman correlation coefficient. Receiver operating characteristic curves were plotted using mortality as the classification variable and the biomarker levels on admission as the prognostic variables. Results : A total of 70 patients with COVID-19 were included in the final analysis. Of all studied biomarkers, s100b had the best predictive ability for death in the intensive care unit, with an area under the curve of 0.73 (0.61-0.83), P = 0.0003. S100b levels correlated with NSE, interleukin (IL)-8, and IL-10 (0.27 < rs < 0.37, P < 0.05), and tended to correlate with suPAR ( rs = 0.26, P = 0.05), but not with the vasopressor dose ( P = 0.62). Conclusion : Among the investigated biomarkers, s100b demonstrated the best predictive ability for death in COVID-19 patients. The overall biomarker profile of the patients implies direct involvement of the nervous system by the novel coronavirus.

Neurologic manifestations of COVID-19 in critically ill patients: results of the prospective multicenter registry PANDEMIC.

BACKGROUND: Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients. METHODS: In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome. RESULTS: Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients. CONCLUSIONS: Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.

Neurological Sequelae of COVID-19.

BACKGROUND: Though primarily a pulmonary disease, Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19. The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders. OBJECTIVE: In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments. METHODS: A literature review was carried out by the authors using PubMed with the search terms "COVID-19" and "Neurology", "Neurological Manifestations", "Neuropsychiatric Manifestations", "Stroke", "Encephalopathy", "Headache", "Guillain-Barre syndrome", "Depression", "Anxiety", "Encephalitis", "Seizure", "Spasm", and "ICUAW". Another search was carried out for "Long-COVID" and "Post-Acute COVID-19" and "Neurological Manifestations" or "Neuropsychiatric Manifestations". Articles such as case reports, case series, and cohort studies were included as references. No language restrictions were enforced. In the case of anxiety and depression, attempts were made to focus mainly on articles describing these conditions in infected patients. RESULTS: A total of 112 articles were reviewed. The incidence, clinical outcomes, and pathophysiology of selected neurological disorders are discussed below. Given the recent advent of this disease, the incidence of certain neurologic sequelae was not always available. Putative mechanisms for each condition in the setting of COVID-19 are outlined.

Mechanisms of coronavirus infectious disease 2019-related neurologic diseases.

PURPOSE OF REVIEW: As of January 8, 2022, a global pandemic caused by infection with severe acute respiratory syndrome coronavirus (SARS-CoV)-2, a new RNA virus, has resulted in 304,896,785 cases in over 222 countries and regions, with over 5,500,683 deaths (www.worldometers.info/coronavirus/). Reports of neurological and psychiatric symptoms in the context of coronavirus infectious disease 2019 (COVID-19) range from headache, anosmia, and dysgeusia, to depression, fatigue, psychosis, seizures, delirium, suicide, meningitis, encephalitis, inflammatory demyelination, infarction, and acute hemorrhagic necrotizing encephalopathy. Moreover, 30-50% of COVID-19 survivors develop long-lasting neurologic symptoms, including a dysexecutive syndrome, with inattention and disorientation, and/or poor movement coordination. Detection of SARS-CoV-2 RNA within the central nervous system (CNS) of patients is rare, and mechanisms of neurological damage and ongoing neurologic diseases in COVID-19 patients are unknown. However, studies demonstrating viral glycoprotein effects on coagulation and cerebral vasculature, and hypoxia- and cytokine-mediated coagulopathy and CNS immunopathology suggest both virus-specific and neuroimmune responses may be involved. This review explores potential mechanistic insights that could contribute to COVID-19-related neurologic disease. RECENT FINDINGS: While the development of neurologic diseases during acute COVID-19 is rarely associated with evidence of viral neuroinvasion, new evidence suggests SARS-CoV-2 Spike (S) protein exhibits direct inflammatory and pro-coagulation effects. This, in conjunction with immune dysregulation resulting in cytokine release syndrome (CRS) may result in acute cerebrovascular or neuroinflammatory diseases. Additionally, CRS-mediated loss of blood-brain barrier integrity in specific brain regions may contribute to the expression of proinflammatory mediators by neural cells that may impact brain function long after resolution of acute infection. Importantly, host co-morbid diseases that affect vascular, pulmonary, or CNS function may contribute to the type of neurologic disease triggered by SARS-COV-2 infection. SUMMARY: Distinct effects of SARS-CoV-2 S protein and CNS compartment- and region-specific responses to CRS may underlie acute and chronic neuroinflammatory diseases associated with COVID-19.

Emerging Knowledge of the Neurobiology of COVID-19.

Many patients with COVID-19 will experience acute or longer-term neuropsychiatric complications. The neurobiological mechanisms behind these are beginning to emerge; however, the neurotropic hypothesis is not strongly supported by clinical data. The inflammatory response to SARS-CoV-2 is likely to be responsible for delirium and other common acute neuropsychiatric manifestations. Vascular abnormalities such as endotheliopathies contribute to stroke and cerebral microbleeds, with their attendant neuropsychiatric sequelae. Longer-term neuropsychiatric syndromes fall into 2 broad categories: neuropsychiatric deficits occurring after severe (hospitalized) COVID-19 and "long COVID," which occurs in many patients with a milder acute COVID-19 illness.

Impact of COVID-19 in Immunosuppressed Children With Neuroimmunologic Disorders.

BACKGROUND AND OBJECTIVES: To investigate whether children receiving immunosuppressive therapies for neuroimmunologic disorders had (1) increased susceptibility to SARS-CoV2 infection or to develop more severe forms of COVID-19; (2) increased relapses or autoimmune complications if infected; and (3) changes in health care delivery during the pandemic. METHODS: Patients with and without immunosuppressive treatment were recruited to participate in a retrospective survey evaluating the period from March 14, 2020, to March 30, 2021. Demographics, clinical features, type of immunosuppressive treatment, suspected or confirmed COVID-19 in the patients or cohabitants, and changes in care delivery were recorded. RESULTS: One hundred fifty-three children were included: 84 (55%) female, median age 13 years (interquartile range [8-16] years), 79 (52%) on immunosuppressive treatment. COVID-19 was suspected or confirmed in 17 (11%) (all mild), with a frequency similar in patients with and without immunosuppressive treatment (11/79 [14%] vs 6/74 [8%], p = 0.3085). The frequency of neurologic relapses was similar in patients with (18%) and without (21%) COVID-19. Factors associated with COVID-19 included having cohabitants with COVID-19 (p < 0.001) and lower blood levels of vitamin D (p = 0.039). Return to face-to-face schooling or mask type did not influence the risk of infection, although 43(28%) children had contact with a classmate with COVID-19. Clinic visits changed from face to face to remote for 120 (79%) patients; 110 (92%) were satisfied with the change. DISCUSSION: In this cohort of children with neuroimmunologic disorders, the frequency of COVID-19 was low and not affected by immunosuppressive therapies. The main risk factors for developing COVID-19 were having cohabitants with COVID-19 and low vitamin D levels.

Neurological Associations of SARS-CoV-2 Infection: A Systematic Review.

BACKGROUND: The current ongoing COVID-19 pandemic has compelled us to scrutinize major outbreaks in the past two decades, Severe Acute Respiratory Syndrome (SARS), in 2002, and Middle East Respiratory Syndrome (MERS), in 2012. We aimed to assess the associated neurological manifestations with SARS CoV-2 infection. METHODS: In this systematic review, a search was carried out by key-electronic databases, controlled vocabulary, and indexing of trials to evaluate the available pertinent studies which included both medical subject headings (MeSH) and advanced electronic databases comprising PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL). Peer-reviewed studies published in English and Spanish were considered, which reported data on the neurological associations of individuals with suspected or laboratory-confirmed SARS-CoV-2 infection. Outcomes were nervous signs or symptoms, symptom severity, and diagnoses. RESULTS: Our search identified 45 relevant studies, with 21 case reports, 3 case series, 9 observational studies, 1 retrospective study, 9 retrospective reviews, and 2 prospective reviews. This systematic review revealed that most commonly reported neuronal presentations involved headache, nausea, vomiting and muscular symptoms like fibromyalgia. Anosmia and ageusia, defects in clarity or sharpness of vision (error in visual acuity), and pain may occur in parallel. Notable afflictions in the form of anxiety, anger, confusion, post-traumatic stress symptoms, and post-intensive care syndrome were observed in individuals who were kept in quarantine and those with long-stay admissions in healthcare settings. SARS CoV-2 infection may result in cognitive impairment. Patients with more severe infection exhibited uncommon manifestations, such as acute cerebrovascular diseases (intracerebral haemorrhage, stroke), rhabdomyolysis, encephalopathy, and Guillain-Barré syndrome. CONCLUSION: SARS-CoV-2 patients experience neuronal presentations varying with the progression of the infection. Healthcare professionals should be acquainted with the divergent neurological symptoms to curb misdiagnosis and limit long-term sequelae. Health-care planners and policymakers must prepare for this eventuality, while the ongoing studies increase our knowledge base on acute and chronic neurological associations of this pathogen.

Mini-Review on SARS-CoV-2 Infection and Neurological Manifestations: A Perspective.

The coronavirus, also known as SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-19), with its rapid rate of transmission, has progressed with a great impact on respiratory function and mortality worldwide. The nasal cavity is the promising gateway of SARS-CoV-2 to reach the brain via systemic circulatory distribution. Recent reports have revealed that the loss of involuntary process of breathing control into the brainstem that results in death is a signal of neurological involvement. Early neurological symptoms, like loss of smell, convulsions, and ataxia, are the clues of the involvement of the central nervous system that makes the entry of SARS-CoV-2 further fatal and life-threatening, requiring artificial respiration and emergency admission in hospitals. Studies performed on patients infected with SARS-CoV-2 has revealed three-stage involvement of the Central Nervous System (CNS) in the progression of SARS-CoV-2 infection: Direct involvement of CNS with headache, ataxia, dizziness, altered or impaired consciousness, acute stroke or seizures as major symptoms, peripheral involvement with impaired taste, smell, vision, and altered nociception, and skeletal muscle impairment that includes skeletal muscle disorders leading to acute paralysis in a particular area of the body. In the previous era, most studied and researched viruses were beta coronavirus and mouse hepatitis virus, which were studied for acute and chronic encephalitis and Multiple Sclerosis (MS). Although the early symptoms of SARS-CoV are respiratory pathogenesis, the differential diagnosis should always be considered for neurological perspective to stop the mortalities.

Neurological complications and infection mechanism of SARS-COV-2.

Currently, SARS-CoV-2 has caused a global pandemic and threatened many lives. Although SARS-CoV-2 mainly causes respiratory diseases, growing data indicate that SARS-CoV-2 can also invade the central nervous system (CNS) and peripheral nervous system (PNS) causing multiple neurological diseases, such as encephalitis, encephalopathy, Guillain-Barré syndrome, meningitis, and skeletal muscular symptoms. Despite the increasing incidences of clinical neurological complications of SARS-CoV-2, the precise neuroinvasion mechanisms of SARS-CoV-2 have not been fully established. In this review, we primarily describe the clinical neurological complications associated with SARS-CoV-2 and discuss the potential mechanisms through which SARS-CoV-2 invades the brain based on the current evidence. Finally, we summarize the experimental models were used to study SARS-CoV-2 neuroinvasion. These data form the basis for studies on the significance of SARS-CoV-2 infection in the brain.

Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection.

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test.

COVID-19 and its effects on neurological functions.

Ever since the first reported case series on SARS-CoV-2-induced neurological manifestation in Wuhan, China in April 2020, various studies reporting similar as well as diverse symptoms of COVID-19 infection relating to the nervous system were published. Since then, scientists started to uncover the mechanism as well as pathophysiological impacts it has on the current understanding of the disease. SARS-CoV-2 binds to the ACE2 receptor which is present in certain parts of the body which are responsible for regulating blood pressure and inflammation in a healthy system. Presence of the receptor in the nasal and oral cavity, brain, and blood allows entry of the virus into the body and cause neurological complications. The peripheral and central nervous system could also be invaded directly in the neurogenic or hematogenous pathways, or indirectly through overstimulation of the immune system by cytokines which may lead to autoimmune diseases. Other neurological implications such as hypoxia, anosmia, dysgeusia, meningitis, encephalitis, and seizures are important symptoms presented clinically in COVID-19 patients with or without the common symptoms of the disease. Further, patients with higher severity of the SARS-CoV-2 infection are also at risk of retaining some neurological complications in the long-run. Treatment of such severe hyperinflammatory conditions will also be discussed, as well as the risks they may pose to the progression of the disease. For this review, articles pertaining information on the neurological manifestation of SARS-CoV-2 infection were gathered from PubMed and Google Scholar using the search keywords "SARS-CoV-2", "COVID-19", and "neurological dysfunction". The findings of the search were filtered, and relevant information were included.

Worldwide epidemiology of neuro-coronavirus disease in children: lessons for the next pandemic.

PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has overwhelmed the global community, negatively impacting patient health and research efforts; associated neurological manifestations are a significant cause of morbidity. This review outlines the worldwide epidemiology of neurologic manifestations of different SARS-CoV-2 clinical pediatric phenotypes, including acute coronavirus disease 2019 (COVID-19), multisystem inflammatory syndrome in children (MIS-C) and postacute sequelae of COVID-19 (PASC). We discuss strategies to develop adaptive global research platforms for future investigation into emerging pediatric neurologic conditions. RECENT FINDINGS: Multicenter, multinational studies show that neurological manifestations of acute COVID-19, such as smell/taste disorders, headache, and stroke, are common in hospitalized adults (82%) and children (22%), associated with increased mortality in adults. Neurological manifestations of MIS-C are reported in up to 20% of children, including headache, irritability, and encephalopathy. Data on PASC are emerging and include fatigue, cognitive changes, and headache. Reports of neurological manifestations in each phenotype are limited by lack of pediatric-informed case definitions, common data elements, and resources. SUMMARY: Coordinated, well resourced, multinational investigation into SARS-CoV-2-related neurological manifestations in children is critical to rapid identification of global and region-specific risk factors, and developing treatment and mitigation strategies for the current pandemic and future health neurologic emergencies.

Complication and Sequelae of COVID-19: What Should We Pay Attention to in the Post-Epidemic Era.

COVID-19 is widespread worldwide and seriously affects the daily life and health of humans. Countries around the world are taking necessary measures to curb the spread. However, COVID-19 patients often have at least one organ complication and sequelae in addition to respiratory symptoms. Controlling the epidemic is only a phased victory, and the complication and sequelae of COVID-19 will need more attention in the post-epidemic era. We collected general information from over 1000 articles published in 2020 after the COVID-19 outbreak and systematically analyzed the complication and sequelae associated with eight major systems in COVID-19 patients caused by ACE2 intervention in the RAS regulatory axis. The autoimmune response induced by 2019-nCoV attacks and damages the normal tissues and organs of the body. Our research will help medical workers worldwide address COVID-19 complication and sequelae.