Risk and characteristics of attacks occurring after vaccination in patients with neuromyelitis optica spectrum disorders: A systematic review and meta-analysis.

BACKGROUND: Vaccination in patients with neuromyelitis optica spectrum disorders (NMOSD) is challenging because there is a concern that vaccines can lead to clinical attacks. However, little is known about the risk and the characteristics of attacks occurring after vaccination. METHODS: We performed a systematic review and meta-analysis using PubMed and Embase databases to estimate a summary frequency of attacks occurring after vaccination and describe the clinical features of theses attacks. We defined attacks occurring after vaccination as typical NMOSD attacks that occurred up to 30 days after vaccine administration.  For the frequency of attacks occurring after vaccination, we selected observational studies that reported the number of attacks and total number of patients that received vaccines; for the clinical description of the attacks, case reports and case series were also included. RESULTS: We included 377 participants from 5 studies to estimate the frequency of NMOSD attacks occurring after vaccination. We found a summary frequency of of 2% (95% CI 1-4%, I2 = 0%). We evaluated 17 studies to identify that 13 different vaccines were associated with NMOSD attacks. A higher-than-expected proportion of males, simultaneous optic neuritis and transverse myelitis attacks, and anti-aquaporin 4 antibody negative cases were identified in vaccine-associated attacks from 24 participants from 17 studies. Nearly two-thirds of attacks occurring after vaccination were an initial event of NMOSD. CONCLUSION: The frequency of NMOSD attacks occurring after vaccination is low and non-specific to different vaccine technologies. Our work reinforces the safety of vaccine recommendations in patients with NMOSD.

Autoantibodies to Interferons in Infectious Diseases.

Anti-cytokine autoantibodies and, in particular, anti-type I interferons are increasingly described in association with immunodeficient, autoimmune, and immune-dysregulated conditions. Their presence in otherwise healthy individuals may result in a phenotype characterized by a predisposition to infections with several agents. For instance, anti-type I interferon autoantibodies are implicated in Coronavirus Disease 19 (COVID-19) pathogenesis and found preferentially in patients with critical disease. However, autoantibodies were also described in the serum of patients with viral, bacterial, and fungal infections not associated with COVID-19. In this review, we provide an overview of anti-cytokine autoantibodies identified to date and their clinical associations; we also discuss whether they can act as enemies or friends, i.e., are capable of acting in a beneficial or harmful way, and if they may be linked to gender or immunosenescence. Understanding the mechanisms underlying the production of autoantibodies could improve the approach to treating some infections, focusing not only on pathogens, but also on the possibility of a low degree of autoimmunity in patients.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Anti-synthetase syndrome masquerading as recurrent pneumonia.

Anti-synthetase syndrome (ASS) is a rare inflammatory myopathy with a wide variety of clinical presentations. ASS-related interstitial lung disease (ASS-ILD) presents with rapid onset and progression, which could often be confused with other more common acute processes such as pneumonia, especially when ILD can be the sole manifestation. A woman in her 50s presented with recurrent dyspnoea for 2 months requiring multiple hospital admissions, and each time, she was diagnosed with multifocal pneumonia and treated with antibiotics. On admission, the evaluation revealed a markedly elevated creatine kinase level at 3258 U/L and a CT scan of the chest revealed worsening scattered ground-glass opacities. Given the concern for ILD as the cause of antibiotic failure, she underwent bronchoscopy with bronchoalveolar lavage which revealed non-specific interstitial pneumonia. A subsequent myositis panel revealed a positive anti-Jo-1 antibody, and she was diagnosed with ASS-ILD. She completed a course of intravenous immunoglobulin and methylprednisolone and experienced significant clinical improvement with the resolution of hypoxaemia and improved polyarthralgia.ASS could often be misdiagnosed as other more common acute lung processes, as a clinically subtle course can escape detection given its rarity, as well as its non-specific and highly variable presentations. This case highlights the importance of early suspicion and consideration of performing specific autoantibody testing when evaluating patients with a suspicion of undifferentiated autoimmune condition.

Overview of autoantibodies in COVID-19 convalescents.

Accumulating evidence shows that SARS-CoV-2 can potentially trigger autoimmune processes, which can be responsible for the long-term consequences of COVID-19. Therefore, this paper aims to review the autoantibodies reported in COVID-19 convalescents. Six main groups were distinguished: (i) autoantibodies against components of the immune system, (ii) autoantibodies against components of the cardiovascular system, (iii) thyroid autoantibodies, (iv) autoantibodies specific for rheumatoid diseases, (v) antibodies against G-protein coupled receptors, and (vi) other autoantibodies. The evidence reviewed here clearly highlights that SARS-CoV-2 infection may induce humoral autoimmune responses. However, the available studies share number of limitations, such as: (1) the sole presence of autoantibodies does not necessarily implicate the clinically-relevant risks, (2) functional investigations were rarely performed and it is often unknown whether observed autoantibodies are pathogenic, (3) the control seroprevalence, in healthy, noninfected individuals was often not reported; thus it is sometimes unknown whether the detected autoantibodies are the result of SARS-CoV-2 infection or the accidental post-COVID-19 detection, (4) the presence of autoantibodies was rarely correlated with symptoms of the post-COVID-19 syndrome, (5) the size of the studied groups were often small, (6) the studies focused predominantly on adult populations, (7) age- and sex-related differences in seroprevalence of autoantibodies were rarely explored, (8) genetic predispositions that may be involved in generation of autoantibodies during SARS-CoV-2 infections were not investigated, and (9) the autoimmune reactions following infection with SARS-CoV-2 variants that vary in the clinical course of infection remain unexplored. Further longitudinal studies are advocated to assess the link between identified autoantibodies and particular clinical outcomes in COVID-19 convalescents.

Neuro-Ophthalmic Visual Impairment in the Setting of COVID-19.

We set out to describe in detail the afferent neuro-ophthalmological complications that have been reported in association with coronavirus disease 2019 (COVID-19) infection. We describe and elaborate on mechanisms of disease, including para-infectious inflammation, hypercoagulability, endothelial damage, and direct neurotropic viral invasion. Despite global vaccination programs, new variants of COVID-19 continue to pose an international threat, and patients with rare neuro-ophthalmic complications are likely to continue to present for care.Afferent complications from COVID-19 include homonymous visual field loss, with or without higher cortical visual syndromes, resulting from stroke, intracerebral hemorrhage, or posterior reversible leukoencephalopathy. Optic neuritis has frequently been reported, sometimes along with acute disseminated encephalomyelopathy, often in association with either myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) or less commonly aquaporin-4 seropositivity or in newly diagnosed multiple sclerosis. Ischemic optic neuropathy has rarely been reported. Papilledema, resulting either from venous sinus thrombosis or idiopathic intracranial hypertension in the setting of COVID-19, has also been described.Observed afferent neuro-ophthalmic associations need to be confirmed though larger comparative studies. Meanwhile, the range of possible complications should be recognized by neurologists and ophthalmologists alike, to facilitate faster diagnosis and treatment of both COVID-19 and its neuro-ophthalmic manifestations.

The chemokine landscape: one system multiple shades.

Leukocyte trafficking is mainly governed by chemokines, chemotactic cytokines, which can be concomitantly produced in tissues during homeostatic conditions or inflammation. After the discovery and characterization of the individual chemokines, we and others have shown that they present additional properties. The first discoveries demonstrated that some chemokines act as natural antagonists on chemokine receptors, and prevent infiltration of leukocyte subsets in tissues. Later on it was shown that they can exert a repulsive effect on selective cell types, or synergize with other chemokines and inflammatory mediators to enhance chemokine receptors activities. The relevance of the fine-tuning modulation has been demonstrated in vivo in a multitude of processes, spanning from chronic inflammation to tissue regeneration, while its role in the tumor microenvironment needs further investigation. Moreover, naturally occurring autoantibodies targeting chemokines were found in tumors and autoimmune diseases. More recently in SARS-CoV-2 infection, the presence of several autoantibodies neutralizing chemokine activities distinguished disease severity, and they were shown to be beneficial, protecting from long-term sequelae. Here, we review the additional properties of chemokines that influence cell recruitment and activities. We believe these features need to be taken into account when designing novel therapeutic strategies targeting immunological disorders.

Autoantigen profiling reveals a shared post-COVID signature in fully recovered and long COVID patients.

Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as long COVID. The underlying pathophysiology of long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of SARS-CoV-2 infection and certain other post-COVID sequelae, their potential role in long COVID is important to investigate. Here, we apply a well-established, unbiased, proteome-wide autoantibody detection technology (T7 phage-display assay with immunoprecipitation and next-generation sequencing, PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected that separated individuals with prior SARS-CoV-2 infection from those never exposed to SARS-CoV-2, we did not detect patterns of autoreactivity that separated individuals with long COVID from individuals fully recovered from COVID-19. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and long COVID was apparent by this assay.

SARS-CoV-2 Positive Serology and Islet Autoantibodies in Newly Diagnosed Pediatric Cases of Type 1 Diabetes Mellitus: A Single-Center Cohort Study.

Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although presenting less severe forms of the disease in children, seems to play a role in the development of other conditions, including type 1 diabetes mellitus (T1DM). After the beginning of the pandemic, an increase in the number of T1DM pediatric patients was observed in several countries, thus leading to many questions about the complex relationship between SARS-CoV-2 infection and T1DM. Our study aimed to highlight possible correlations between SARS-CoV-2 serology and T1DM onset. Therefore, we performed an observational retrospective cohort study that included 158 children diagnosed with T1DM in the period April 2021-April 2022. The presence or absence of SARS-CoV-2 and T1DM-specific antibodies and other laboratory findings were assessed. In the group of patients with positive SARS-CoV-2 serology, a higher percentage had detectable IA-2A antibodies, more children were positive for all three islet autoantibodies determined (GADA, ICA, and IA-2A), and a higher mean HbA1c value was found. No difference existed between the two groups regarding DKA presence and severity. A lower C-peptide level was found in the patients presenting diabetic ketoacidosis (DKA) at T1DM onset. When compared to a group of patients diagnosed before the pandemic, an increased incidence of both DKA and severe DKA, as well as a higher age at diagnosis and higher levels of HbA1c were present in our study group. These findings have important implications for the ongoing monitoring and management of children with T1DM after the COVID-19 pandemic and highlight the need for further research to better understand the complex relationship between SARS-CoV-2 infection and T1DM.

Frequency and Referral Patterns of Neural Antibody Studies During the COVID-19 Pandemic: Experience From an Autoimmune Neurology Center.

OBJECTIVE: To determine whether the frequency of paraneoplastic or autoimmune encephalitis antibodies examined in a referral center changed during the COVID-19 pandemic. METHODS: The number of patients who tested positive for neuronal or glial (neural) antibodies during pre-COVID-19 (2017-2019) and COVID-19 (2020-2021) periods was compared. The techniques used for antibody testing did not change during these periods and included a comprehensive evaluation of cell-surface and intracellular neural antibodies. The chi-square test, Spearman correlation, and Python programming language v3 were used for statistical analysis. RESULTS: Serum or CSF from 15,390 patients with suspected autoimmune or paraneoplastic encephalitis was examined. The overall positivity rate for antibodies against neural-surface antigens was similar in the prepandemic and pandemic periods (neuronal 3.2% vs 3.5%; glial 6.1 vs 5.2) with a mild single-disease increase in the pandemic period (anti-NMDAR encephalitis). By contrast, the positivity rate for antibodies against intracellular antigens was significantly increased during the pandemic period (2.8% vs 3.9%, p = 0.01), particularly Hu and GFAP. DISCUSSION: Our findings do not support that the COVID-19 pandemic led to a substantial increase of known or novel encephalitis mediated by antibodies against neural-surface antigens. The increase in Hu and GFAP antibodies likely reflects the progressive increased recognition of the corresponding disorders.

The multifactorial complexities of autoimmune development in Pemphigus vulgaris: Critical evaluation of the role of environmental and lifestyle "exposome" factors.

Pemphigus vulgaris (PV) is a potentially life-threatening blistering disorder characterized by autoantibodies directed against cell-cell adhesion molecules that serves as an excellent model to study human autoimmune development. Numerous studies have identified specific Human Leukocyte Antigen (HLA) genes, in particular DRB1*0402 and DQB1*0503, that confer disease risk. Although HLA is required, it is not sufficient for the initiation of disease. As with all autoimmune diseases, the etio-pathogenesis of PV is complex, meaning it is multifactorial. Susceptibility is polygenic, and the search for non-HLA disease-linked genes continues. Moreover, twin studies across autoimmune conditions indicate that non-genetic environmental and lifestyle factors, which can be collectively grouped under the term "exposome", are also major contributors to disease development. The literature presents evidence for the potential role of multiple triggers such as medications, infections, stress, diet, immunizations, and sleep to influence the etiology, pathophysiology, and prognosis of PV. However, a clear understanding of the degree to which specific factors impact PV is lacking. In this investigation, we comprehensively review the environmental elements listed above and consider the strength of evidence for these factors. The overall goals of this work are to provide greater insights into the factors that influence disease susceptibility, disease development and disease course and ultimately help to better guide clinicians and inform patients in the management of PV.

Immunopathogenesis of viral infections in neurological autoimmune disease.

Autoimmune diseases develop due to self-tolerance failure in recognizing self and non-self-antigens. Several factors play a role in inducing autoimmunity, including genetic and environmental elements. Several studies demonstrated the causative role of viruses; however, some studies showed the preventive effect of viruses in the development of autoimmunity. Neurological autoimmune diseases are classified based on the targets of autoantibodies, which target intracellular or extracellular antigens rather than neurons. Several theories have been hypothesized to explain the role of viruses in the pathogenesis of neuroinflammation and autoimmune diseases. This study reviewed the current data on the immunopathogenesis of viruses in autoimmunity of the nervous system.

Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination-Induced Myocarditis.

Importance: Cardiac dysfunction and myocarditis have emerged as serious complications of multisystem inflammatory syndrome in children (MIS-C) and vaccines against SARS-CoV-2. Understanding the role of autoantibodies in these conditions is essential for guiding MIS-C management and vaccination strategies in children. Objective: To investigate the presence of anticardiac autoantibodies in MIS-C or COVID-19 vaccine-induced myocarditis. Design, Setting, and Participants: This diagnostic study included children with acute MIS-C or acute vaccine myocarditis, adults with myocarditis or inflammatory cardiomyopathy, healthy children prior to the COVID-19 pandemic, and healthy COVID-19 vaccinated adults. Participants were recruited into research studies in the US, United Kingdom, and Austria starting January 2021. Immunoglobulin G (IgG), IgM, and IgA anticardiac autoantibodies were identified with immunofluorescence staining of left ventricular myocardial tissue from 2 human donors treated with sera from patients and controls. Secondary antibodies were fluorescein isothiocyanate-conjugated antihuman IgG, IgM, and IgA. Images were taken for detection of specific IgG, IgM, and IgA deposits and measurement of fluorescein isothiocyanate fluorescence intensity. Data were analyzed through March 10, 2023. Main Outcomes and Measures: IgG, IgM and IgA antibody binding to cardiac tissue. Results: By cohort, there were a total of 10 children with MIS-C (median [IQR] age, 10 [13-14] years; 6 male), 10 with vaccine myocarditis (median age, 15 [14-16] years; 10 male), 8 adults with myocarditis or inflammatory cardiomyopathy (median age, 55 [46-63] years; 6 male), 10 healthy pediatric controls (median age, 8 [13-14] years; 5 male), and 10 healthy vaccinated adults (all older than 21 years, 5 male). No antibody binding above background was observed in human cardiac tissue treated with sera from pediatric patients with MIS-C or vaccine myocarditis. One of the 8 adult patients with myocarditis or cardiomyopathy had positive IgG staining with raised fluorescence intensity (median [IQR] intensity, 11 060 [10 223-11 858] AU). There were no significant differences in median fluorescence intensity in all other patient cohorts compared with controls for IgG (MIS-C, 6033 [5834-6756] AU; vaccine myocarditis, 6392 [5710-6836] AU; adult myocarditis or inflammatory cardiomyopathy, 5688 [5277-5990] AU; healthy pediatric controls, 6235 [5924-6708] AU; healthy vaccinated adults, 7000 [6423-7739] AU), IgM (MIS-C, 3354 [3110-4043] AU; vaccine myocarditis, 3843 [3288-4748] AU; healthy pediatric controls, 3436 [3313-4237] AU; healthy vaccinated adults, 3543 [2997-4607] AU) and IgA (MIS-C, 3559 [2788-4466] AU; vaccine myocarditis, 4389 [2393-4780] AU; healthy pediatric controls, 3436 [2425-4077] AU; healthy vaccinated adults, 4561 [3164-6309] AU). Conclusions and Relevance: This etiological diagnostic study found no evidence of antibodies from MIS-C and COVID-19 vaccine myocarditis serum binding cardiac tissue, suggesting that the cardiac pathology in both conditions is unlikely to be driven by direct anticardiac antibody-mediated mechanisms.

Inflammatory Myopathies.

PURPOSE OF REVIEW: This article outlines the salient clinical, serologic, electrophysiologic, imaging, and histopathologic findings and treatment options for the idiopathic inflammatory myopathies, including those related to immune checkpoint inhibitors and SARS-CoV-2. RECENT FINDINGS: The classification of idiopathic inflammatory myopathies has improved with the integration of myositis-specific antibodies and histopathologic findings. Characteristic features of immune checkpoint inhibitor-related myositis have been identified, allowing early recognition and treatment of the syndrome. The COVID-19 pandemic has had a profound impact on the care of patients with idiopathic inflammatory myopathies, and several mechanisms of virus-related muscle injury have been proposed. SUMMARY: A comprehensive evaluation including clinical examination, EMG, imaging, antibody testing, muscle biopsy, and cancer screening, when appropriate, can lead to an earlier accurate diagnosis and an individualized treatment approach for patients with idiopathic inflammatory myopathies.

The risk for celiac disease after Covid-19 infection.

BACKGROUND: Celiac disease (CD) is an autoimmune disease leading to gastrointestinal symptoms and mineral deficiencies. The pathogenetic mechanisms, besides the clear HLA association, are elusive. Among environmental factors infections have been proposed. Covid-19 infection results in a systemic inflammatory response that often also involves the gastrointestinal tract. The aim of the present study was to investigate whether Covid-19 infection could increase the risk for CD. PATIENTS AND METHODS: All patients, both children and adults, in the county Skåne (1.4 million citizens) in southern Sweden with newly diagnosed biopsy- or serology-verified CD or a positive tissue transglutaminase antibody test (tTG-ab) during 2016-2021 were identified from registries at the Departments of Pathology and Immunology, respectively. Patients with a positive Covid-19 PCR or antigen test in 2020 and 2021 were identified from the Public Health Agency of Sweden. RESULTS: During the Covid-19 pandemic (March 2020 - December 2021), there were 201 050 cases of Covid-19 and 568 patients with biopsy- or serology-verified CD or a first-time positive tTG-ab tests, of which 35 patients had been infected with Covid-19 before CD. The incidence of verified CD and tTG-ab positivity was lower in comparison to before the pandemic (May 2018 - February 2020; 22.5 vs. 25.5 cases per 100 000 person-years, respectively, incidence rate difference (IRD) -3.0, 95% CI -5.7 - -0.3, p = 0.028). The incidence of verified CD and tTG-ab positivity in patients with and without prior Covid-19 infection was 21.1 and 22.4 cases per 100 000 person-years, respectively (IRD - 1.3, 95% CI -8.5-5.9, p = 0.75). CONCLUSIONS: Our results indicate that Covid-19 is not a risk factor for CD development. While gastrointestinal infections seem to be an important part of the CD pathogenesis, respiratory infections probably are of less relevance.

Autoantibodies against type I interferons in COVID-19 infection: A systematic review and meta-analysis.

OBJECTIVES: In this study, we aimed to study the rate of autoantibodies against type I interferons (IFNs) in patients with COVID-19 and analyze its dependence on severity of infection and some other variables. METHODS: A systemic review with the search terms: "COVID-19" or "SARS-CoV-2" and "autoantibodies" or "autoantibody" and "IFN" or "interferon" for the period 20 December 2019 to 15 August 2022 was carried out using PubMed, Embase, Cochrane, and Web of Science. R 4.2.1 software was used for meta-analysis of the published results. Pooled risk ratios and 95% confidence intervals (CIs) were calculated. RESULTS: We identified eight studies involving 7729 patients, of whom 5097 (66%) had severe COVID-19 and 2632 (34%) had mild or moderate symptoms. The positive rate of anti-type-I-IFN-autoantibodies in the total dataset was 5% (95% CI, 3-8%), but reached 10% (95% CI, 7-14%) in those with severe infection. The most common subtypes were anti-IFN-α (89%) and anti-IFN-ω (77%). The overall prevalence in male patients was 5% (95% CI, 4-6%), and in female patients 2% (95% CI, 1-3%). CONCLUSION: Severe COVID-19 is associated with high rates of autoantibodies against type-I-IFN and more so in male than female patients.

Is COVID-19 severity unrelated to antinuclear antibodies?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces an overreaction of the immune system, resulting in the production of auto-antibodies. Several studies have reported that autoantibodies are prevalent in COVID-19 patients. In our study, antinuclear antibodies were evaluated in patients with COVID-19. We examined 131 sera from patients (>17-year-old) with confirmed COVID-19. Samples were collected prior to receiving any medication and antinuclear antibodies (ANA) levels were measured by the indirect immunofluorescence (IIF) method. Furthermore, the immunoblotting test was used to determine the presence of anti-nuclear antigen antibodies. The IIF-ANA test was positive in 36.4% (48/131) of patients. Overall, non-ICU patients had higher IIF-ANA titers than ICU patients. In particular, ICU patients had fewer nuclear, cytoplasmic, and mitotic IIF-ANA antibodies than non-ICU patients. In conclusion, COVID-19 patients frequently have ANA possibly reflecting the immune dysregulation due to several damaged cells by SARS-CoV-2 virus.

COVID-19 and the Pandemic-Related Aspects in Pediatric Demyelinating Disorders.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as Coronavirus-19 (COVID-19) infection, has been associated with several neurological symptoms, including acute demyelinating syndromes (ADS). There is a growing body of literature discussing COVID-19 and demyelinating conditions in adults; however, there is less published about COVID-19 demyelinating conditions in the pediatric population. This review aims to discuss the impact of COVID-19 in pediatric patients with central nervous system ADS (cADS) and chronic demyelinating conditions. We reviewed PubMed, Google Scholar, and Medline for articles published between December 1, 2019 and October 25, 2022 related to COVID-19 and pediatric demyelinating conditions. Of 56 articles reviewed, 20 cases of initial presentation of ADS associated with COVID-19 were described. The most commonly described cADS associated with COVID-19 infection in children was Acute Disseminated Encephalomyelitis followed by Transverse Myelitis. Cases of Myelin Oligodendrocyte Glycoprotein Antibody Disease, Neuromyelitis Optica Spectrum Disorder, and Multiple Sclerosis are also described. The risk of severe COVID-19 in pediatric patients with demyelinating conditions appears low, including in patients on disease modifying therapies, but studies are limited. The pandemic did affect disease modifying therapies in ADS, whether related to changes in prescriber practice or access to medications. COVID-19 is associated with ADS in children and the COVID-19 pandemic has impacted pediatric patients with demyelinating conditions in various ways.