Impact of SARS-CoV-2 on the nervous system

Introduction. The ongoing COVID-19 pandemic is the largest global public health struggle. The spread of the novel coronavirus had resulted in almost 7 million deaths worldwide by January 2023. State of the art. The most common symptoms during the acute phase of COVID-19 are respiratory. However, many individuals present various neurological deficits at different stages of the infection. Furthermore, there are post-infectious complications that can be present within weeks after the initial symptoms. Both the central and peripheral nervous systems (CNS and PNS, respectively) can be affected. Many potential mechanisms and hypotheses regarding the neuropathology behind COVID-19 have been proposed. Clinical implications. The distribution of neurological symptoms during COVID-19 infection among studies differs greatly, which is mostly due to differing inclusion criteria. One of the most significant is incidence involving CNS circulation. In this review, we present basic information regarding the novel coronavirus, the possible routes along which the pathogen can reach the nervous system, neuropathology mechanisms, and neurological symptoms following COVID-19. Future directions. It seems that many factors, resulting both from the properties of the virus and from systemic responses to infection, play a role in developing neurological symptoms. The long-term effect of the virus on the nervous system is still unknown

Clinical and epidemiological characteristics of multiple sclerosis patients receiving disease-modifying treatment in Poland

Aim of study. The aim of this study was to collect and analyse data on relapsing-remitting multiple sclerosis (RRMS) patients receiving disease-modifying therapies (DMTs) in Poland.Material and methods. This observational, multicentre study with prospective data collection included RRMS patients receiving DMTs reimbursed by the National Health Fund (NFZ) in Poland, monitored by the Therapeutic Programme Monitoring System (SMPT). Demographic profiles, disability status, and treatment modalities were analysed.Results. Data from 11,632 RRMS patients was collected (from 15,368 new prescriptions), including 10,649 patients in the first-line and 983 in the second-line therapeutic programme of DMTs. The proportion of females to males was 2.39 in the first-line and 1.91 in the second-line. The mean age at DMTs start was 36.6 years in the first-line and 35.1 in the second-line. The median time from the first symptoms to MS diagnosis was 7.4 months, and from MS diagnosis to treatment it was 18.48 months. A total of 43.4% of MS patients started DMT during the 12 months following diagnosis. There was a positive correlation between the duration from MS diagnosis to the start of DMT and a higher initial EDSS value [correlation 0.296 (p < 0.001)]. About 10% of patients stopped DMTs. In Poland, about one third of all MS patients are treated in both lines, and the choice of first-line treatment depends on the region of the country.Conclusions. In Poland there is a need to increase MS patient access to DMTs by improving the organisation of drug programmes

Blood-brain barrier function in response to SARS-CoV-2 and its spike protein

The typical manifestation of coronavirus 2 (CoV-2) infection is a severe acute respiratory syndrome (SARS) accompanied by pneumonia (COVID-19). However, SARS-CoV-2 can also affect the brain, causing chronic neurological symptoms, variously known as long, post, post-acute, or persistent COVID-19 condition, and affecting up to 40% of patients. The symptoms (fatigue, dizziness, headache, sleep disorders, malaise, disturbances of memory and mood) usually are mild and resolve spontaneously. However, some patients develop acute and fatal complications, including stroke or encephalopathy. Damage to the brain vessels mediated by the coronavirus spike protein (S-protein) and overactive immune responses have been identified as leading causes of this condition. However, the molecular mechanism by which the virus affects the brain still needs to be fully delineated. In this review article, we focus on interactions between host molecules and S-protein as the mechanism allowing the transit of SARS-CoV-2 through the blood-brain barrier to reach the brain structures. In addition, we discuss the impact of S-protein mutations and the involvement of other cellular factors conditioning the pathophysiology of SARS-CoV-2 infection. Finally, we review current and future COVID-19 treatment options

Association between polymorphisms of a folate – homocysteine – methionine – SAM metabolising enzyme gene and multiple sclerosis in a Polish population

Background and Objectives. Multiple sclerosis (MS) is a chronic inflammatory, autoimmune disease with a still unknown aetiology. The main initial mechanism of demyelination and injury to the central nervous system (CNS) appears to be inflammation. Neurotoxicity induced by homocysteine (Hcy) may be a factor affecting this process. 5,10-methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in Hcy metabolism. It leads to Hcy remethylation to methionine. In the present study, we aimed to investigate a possible association between two variants of MTHFR gene in patients with MS in Poland and healthy individuals.Methods. In this study, we genotyped 174 relapsing-remitting MS patients and 186 healthy controls using the TaqMan technique.Results and Conclusions. It was found that, regardless of the presence of a specific allele, the gender of MS patients affects age at the time of the clinical onset of the disease: in rs1801133 for the C allele and T, the average age was 35 years for women and 29 for men (p = 0.0004; p = 0.034 respectively). Similarly for the second polymorphism rs1801131 for the A allele and C, the average age was 35 years for women and 29 for men (p = 0.001; p = 0.01 respectively). No significant allelic / genotypic frequency differences have been observed between the studied groups (c.677C > T, CT/TT p = 0.719, p = 0.262; c.1298A > C, AC/CC of p = 0.686; p = 0.66). We found no association between polymorphisms of a folate-homocysteine-methionine-SAM metabolising gene enzyme and multiple sclerosis in a Polish population

Antibodies against SARS-CoV-2 S and N proteins in relapsing-remitting multiple sclerosis patients treated with disease-modifying therapies

Clinical rationale for the study. The course of COVID-19 in people with multiple sclerosis (PwMS) has been described, while the serological status after SARS-CoV-2 infection or vaccination, especially in patients treated with disease-modifying therapies (DMT), is still under investigation. This is a significant clinical problem, as certain DMTs may predispose to a severe course of viral infections. Aim of the study. We analyzed the presence of antibodies against spike (S) and nucleocapsid (N) proteins of SARS-CoV-2 in relapsing-remitting PwMS treated with DMT, especially dimethyl fumarate, interferon beta, and glatiramer acetate, in a single multiple sclerosis (MS) centre in north-eastern Poland (the Department of Neurology, Medical University of Bialystok). Material and methods. The presence of antibodies against S and N proteins in PwMS was assessed twice: on visit one (between May and June 2020) (n = 186) and on visit two (between May and June 2021) (n = 88). Samples were taken from 68 individuals on both visits. Demographic and clinical data was collected: duration of MS, Expanded Disability Status Scale Score (EDSS), type of DMT, history of COVID-19 (positive PCR or antigen test in the past), vaccination status, and the type of vaccine. Results. It was shown that on visit one: 3.7% (n = 7) PwMS were positive for IgA against S protein (IgA-S), 3.2% (n = 6) for IgG against S (IgG-S) protein, and none of those examined was positive for IgG against N protein (IgG-N). On visit two, the most common detected antibodies were IgG-S (71.3%; n = 62), then IgA-S (65.1%; n = 55), and the least common was IgG-N (18.2%; n = 16). On visit two: 20.45% of PwMS had a history of a positive SARS-CoV-2 PCR or antigen test during the last year. By the time of visit two, 42.05% (n = 37) of patients who participated in visit two had been full-course vaccinated against COVID-19. It was demonstrated that vaccination against SARS-CoV-2 significantly induces the production of IgG-S and IgA-S (p < 0.0001), while no difference between vaccinated and unvaccinated patients was shown in the detection of IgG-N. There was no correlation between COVID-19 infection and antibodies against proteins S and N in the study group. Moreover, the presented study did not show any relationship between the ability to produce antibodies against the S protein with any of the used DMTs. Conclusions and clinical implications. According to our study, PwMS treated with dimethyl fumarate, interferon beta, or glatiramer acetate can efficiently produce antibodies against SARS-CoV-2 both after infection and after vaccination

Sense of happiness in Polish patients with multiple sclerosis

Introduction. Happiness is crucial to patient well-being and their acceptance of their disease. The aim of this study was to assess the sense of happiness in persons with multiple sclerosis (PwMS), compare it to the level of happiness in patients with other neurological conditions, and determine which factors affect the sense of happiness in PwMS. Material and methods. Five hundred and eighty-nine PwMS and 145 control subjects (post-stroke patients with chronic pain syndromes and neuropathies) were included in the study. Due to the differences between the groups in terms of demographic variables, an adjusted group of PwMS (n = 145) was selected from the entire group of PwMS. All patients were assessed using the Oxford Happiness Questionnaire (OHQ), the Satisfaction with Life Scale (SLS), and the Family APGAR Questionnaire. Based on regression analysis, the study examined which variables affected the level of happiness in the groups. Results. Analysis of the OHQ scores showed that PwMS had a lower sense of happiness compared to the control group in the overall score [113.21 (25–42) vs. 119.88 (25–49), respectively; p = 0.031] and the subscales (OHQ subscale 1 — 54.52 vs. 57.84, respectively; p = 0.027; subscale 2 — 35.61 vs. 37.67; respectively; p = 0.044). Based on linear regression analysis, life satisfaction (β = 0.40; p < 0.001), positive orientation (β = 0.32; p < 0.001), and primary education (β = 0.08; p = 0.009) were the most significant predictors of a higher level of happiness in PwMS. Similar results were found in the control group. Conclusions. The sense of happiness in PwMS was lower than in patients with other conditions. The most important factors influencing happiness included life satisfaction and positive orientation. Influencing these predictors should be the aim of psychological interventions, especially in patients with a reduced sense of happiness

Clinical course and outcome of SARS-CoV-2 infection in multiple sclerosis patients treated with disease-modifying therapies — the Polish experience

Introduction. The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited.Materials and methods. This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health.Results. There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used.Conclusions and clinical implications. Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs