SARS-CoV-2 neurotropism and other possible causes of olfactory disorders in COVID-19.

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease (AIRD) caused by infection with the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first cases were diagnosed and reported in Wuhan, central China, in November 2019. The disease initially occurred locally. However, the number of infected individuals increased dynamically and spread worldwide. The most common symptoms of the SARS-CoV-2 infection include malaise, fever, dry cough and dyspnoea. Over time, reports of new COVID-19 symptoms included taste and smell disorders. A potential cause of these disorders is related to neurotropism, i.e. the affinity of SARS-CoV-2 to the nervous system. Angiotensin-converting enzyme 2 receptor is essential in the pathogenesis of SARS-CoV-2 infection. The receptor is found in many tissues and organs, including the olfactory epithelium, neurons and neuroglial cells. Another potential cause is neuroinvasiveness, i.e. the ability of the virus to invade the central nervous system, and thereby damage its structures. As a result, olfactory disorders may occur. Other concepts, such as the inflammatory response of the body and the concept of stroke or damage to olfactory supporting cells, are also considered.

COVID-19 and autoimmune diseases of the nervous system - an update.

INTRODUCTION: Due to a similar pathomechanism, COVID-19 infection may significantly affect the course of autoimmune diseases (AIDs). In our review, we aimed to assess the severity of SARS-CoV-2 infection, response to treatment, and the impact of COVID-19 infection on the course of the underlying disease in patients with neuroimmune diseases. STATE OF THE ART: In the time of the COVID-19 pandemic, it was important to determine the influence of COVID-19 infection on the course of autoimmune diseases due to the weakened immune system and immunosuppressive therapies. CLINICAL IMPLICATIONS: Many reports have indicated that in patients with AIDs, the existence of the disease is not associated with a worse prognosis in the course of the viral infection. Patients in advanced stages of the disease, elderly patients, and those with comorbidities are at risk of more frequent hospitalisations and higher mortality in the course of COVID-19. Moreover, some drugs used in AIDs have been tested for their efficacy in SARS-CoV-2 infection. Episodes of newly diagnosed myasthenia gravis, Guillain-Barré syndrome, acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica spectrum disorder (NMOSD) secondary to COVID-19 or vaccination have also been reported. Vaccination against this pathogen is highly recommended in most patients with AIDs. FUTURE DIRECTIONS: Despite many studies on the association between COVID-19 and neuroimmune diseases, more specific data is needed. The approach to patients with AIDs should be individual, since many issues remain unresolved despite the long-lasting pandemic.

Analysis of Side Effects Following Vaccination Against COVID-19 Among Individuals With Multiple Sclerosis Treated With DMTs in Poland.

Background and Objectives: Since vaccination against COVID-19 is available for over a year and the population of immunized individuals with autoimmune disorders is higher than several months before, an evaluation of safety and registered adverse events can be made. We conducted a large study of side effects following the COVID-19 vaccine among patients with multiple (MS) sclerosis treated with disease-modifying therapies (DMTs) and analyzed factors predisposing for particular adverse events. Methods: We gathered data of individuals with MS treated with DMTs from 19 Polish MS Centers, who reported at least one adverse event following COVID-19 vaccination. The information was obtained by neurologists using a questionnaire. The same questionnaire was used at all MS Centers. To assess the relevance of reported adverse events, we used Fisher's exact test, t-test, and U-Menn-Whutney test. Results: A total of 1,668 patients with MS and reports of adverse events after COVID-19 vaccination were finally included in the study. Besides one case marked as "red flag", all adverse events were classified as mild. Pain at the injection site was the most common adverse event, with a greater frequency after the first dose. Pain at the injection site was significantly more frequent after the first dose among individuals with a lower disability (EDSS ≤2). The reported adverse events following immunization did not differ over sex. According to age, pain at the injection site was more common among individuals between 30 and 40 years old, only after the first vaccination dose. None of the DMTs predisposed for particular side effects. Conclusions: According to our findings, vaccination against COVID-19 among patients with MS treated with DMTs is safe. Our study can contribute to reducing hesitancy toward vaccination among patients with MS.

Post-COVID­19 complications in hospitalized and nonhospitalized patients: the Silesian database of COVID­19 complications (SILCOV­19).

INTRODUCTION: Due to the extent of the pandemic, high prevalence and severity of complications in the early post­recovery period are expected. OBJECTIVES: This study aimed to compare the scope of early post-COVID­19 complications in patients who had the disease and were or were not hospitalized. PATIENTS AND METHODS: This was a prospective, observational, registry­based cohort study conducted at a tertiary cardiovascular hospital in Silesia, Poland. Interdisciplinary diagnostics, including cardiovascular, pneumatological, respiratory, neurological, and psychiatric tests, was performed during the study visit. All patients completed the study. Two­hundred unselected, adult, white men and women with the symptoms of acute COVID­19 were included, of which 86 patients had the disease but did not require hospitalization. RESULTS: The median (interquartile range) time from symptom onset to the study visit was 107 (87-117) and 105 (79-127) days in nonhospitalized and hospitalized patients, respectively. Lung lesions on high­resolution computed tomography were found in 10 (8.8%) and 33 (39.3%) of nonhospitalized and hospitalized patients, respectively (P <0.01); no lesions were visualized on chest X­ray images. Elevated platelet distribution width was found in more than 70% of the patients in both groups. More than half of the patients had insomnia, regardless of the hospitalization status. CONCLUSIONS: The abnormal platelet parameters, functional and radiological findings in the lungs, and insomnia were the most frequent short­term COVID­19 complications in hospitalized and nonhospitalized patients. Considering the number of patients who have had COVID­19 worldwide, a high burden of the post-COVID­19 complications might be expected.

Safety of Vaccines against SARS-CoV-2 among Polish Patients with Multiple Sclerosis Treated with Disease-Modifying Therapies.

(1) Background: The present study aims to report the side effects of vaccination against coronavirus disease 2019 (COVID-19) among patients with multiple sclerosis (MS) who were being treated with disease-modifying therapies (DMTs) in Poland. (2) Methods: The study included 2261 patients with MS who were being treated with DMTs, and who were vaccinated against COVID-19 in 16 Polish MS centers. The data collected were demographic information, specific MS characteristics, current DMTs, type of vaccine, side effects after vaccination, time of side-effect symptom onset and resolution, applied treatment, relapse occurrence, and incidence of COVID-19 after vaccination. The results were presented using maximum likelihood estimates of the odds ratio, t-test, Pearson's chi-squared test, Fisher's exact p, and logistic regression. The statistical analyses were performed using STATA 15 software. (3) Of the 2261 sampled patients, 1862 (82.4%) were vaccinated with nucleoside-modified messenger RNA (mRNA) vaccines. Mild symptoms after immunization, often after the first dose, were reported in 70.6% of individuals. Symptoms included arm pain (47.5% after the first dose and 38.7% after the second dose), fever/chills/flu-like symptoms (17.1% after the first dose and 20.5% after the second dose), and fatigue (10.3% after the first dose and 11.3% after the second dose). Only one individual presented with severe side effects (pro-thrombotic complications) after vaccination. None of the DMTs in the presented cohort were predisposed to the development of side effects. Nine patients (0.4%) had a SARS-CoV-2 infection confirmed despite vaccination. (4) Conclusions: Vaccination against SARS-CoV-2 is safe for people with MS who are being treated with DMTs. Most adverse events following vaccination are mild and the acute relapse incidence is low.

Bilateral paralysis of peroneal nerve after COVID-19 disease: a case report.

BACKGROUND: COVID-19, caused by a novel coronavirus SARS-CoV 2 has rapidly developed into pandemic. This infectious disease affecting mainly respiratory system may cause multiple systemic disorders. With increasing number of new infected patients there are more and more cases with neurological complications secondary to COVID-19. CASE PRESENTATION: Here we present a case of 67-years old Polish male with previously no comorbidities, who has developed bilateral paralysis of peroneal nerve after SARS-CoV 2 infection. Prior to the hospitalization he presented cough and fever and weakness. RT-PCR was reported positive for COVID-19 infection. Then he developed pneumonia and respiratory failure with bilateral lung consolidations on radiological examination. Laboratory findings revealed elevated levels of D-dimer, CRP, AspAT, GGTP, PCT and serum glucose. After discharge from hospital he was diagnosed with thrombophlebitis and prediabetes on follow-up visits. Due to problems with walking, numbness of toes and involuntary muscle spasms in hands, the patient went to the Neurological Outpatient Clinic. After neurological examination bilateral paralysis of peroneal nerve was revealed. CONCLUSIONS: In this report we want to highlight one of the unexpected presentations of SARS-CoV 2 infection and emphasize the importance of neurological examination in COVID-19 patients.

Symptoms after COVID-19 Infection in Individuals with Multiple Sclerosis in Poland.

(1) Background: To report and analyze the presence of residual symptoms after SARS-CoV-2 infection among Polish patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs). (2) Methods: The study included 426 individuals with MS treated with DMTs and confirmed SARS-CoV-2 infection from 12 Polish MS centers. The data were collected through to 31 May 2021. The information included demographics, specific MS characteristics, course of SARS-CoV-2 infection, and residual (general and neurological) symptoms lasting more than four and 12 weeks after the initial infection. The results were obtained using maximum likelihood estimates for odds ratio and logistic regression. (3) Results: A total of 44.84% patients with MS reported symptoms lasting between four and 12 weeks after the initial infection; 24.41% people had symptoms that resolved up to 12 weeks, and 20.42% patients had symptoms that lasted over 12 weeks. The most common symptoms were: fatigue, disturbance of concentration, attention, and memory, cognitive complaints, and headache. None of the DMTs were predisposed to the development of residual symptoms after the initial infection. A total of 11.97% of patients had relapse three months prior or after SARS-CoV-2 infection. (4) Conclusion: Almost half of individuals with MS treated with different DMTs had residual symptoms after SARS-CoV-2 infection. None of the DMTs raised the probability of developing post-acute COVID symptoms.

Anti-severe acute respiratory syndrome coronavirus-2 antibody responses following Pfizer-BioNTech vaccination in a patient with multiple sclerosis treated with ocrelizumab: a case report.

Patients with multiple sclerosis (MS) repeatedly receive therapies that cause B-lymphocyte depletion. This may lead to abnormal immune responses following coronavirus disease 2019 (COVID-19) vaccination, as has been suggested previously. We therefore evaluated post-vaccination immune responses in a patient with MS treated with ocrelizumab. The intervals between ocrelizumab infusions and vaccination were as recommended by the Section of Multiple Sclerosis and Neuroimmunology of the Polish Neurological Society. A reactive immune response was observed in this patient following vaccination. This suggests that appropriate intervals between ocrelizumab infusions and COVID-19 vaccinations may permit the generation of efficacious immune responses in patients receiving B-lymphocyte depleting therapies.

Multiple sclerosis immunomodulatory therapies tested for effectiveness in COVID-19.

INTRODUCTION: The global pandemic of COVID-19 began in Wuhan, China in December 2019. Research into effective therapies has been conducted worldwide. Currently, there is no antiviral treatment and many patients develop a severe course of the disease, including severe respiratory failure. Due to similar pathomechanisms of inflammation in multiple sclerosis (MS) and COVID-19, immunomodulatory drugs that are registered for the treatment of MS are under study in the SARS-CoV-2 infection in clinical trials. MATERIALS AND METHODS: Using clinicaltrials.gov, we found information related to ongoing clinical studies on potential drugs for COVID-19 which are also used in MS therapy. The outcomes of several trials were published on pubmed.ncbi.nlm.nih.gov. RESULTS: There were 18 clinical trials evaluating the effectiveness and safety of interferon-ß, fingolimod, or leflunomide in COVID-19. Some trial outcomes available at pubmed.ncbi.nlm.nih.gov suggested an association of these drug treatments with improvements in signs and symptoms, and the disease course. CONCLUSION: The administration of immunomodulatory drugs in COVID-19 may result in potential beneficial effects probably associated with their anti-inflammatory and antiviral properties. Further research is warranted to confirm the long-term effects of immunomodulatory therapies in patients with COVID-19.

The course of COVID-19 infection in patients with multiple sclerosis-The experience of one center based on the population of Upper Silesia.

BACKGROUND: It is suspected that patients with multiple sclerosis (MS) are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to disability and immunotherapy. The relationship between MS and coronavirus disease 2019 (COVID-19) is uncertain. The aim of the study was to collect and analyze this relationship. METHODS: All MS patients of the Neurological Outpatient Clinic in Zabrze, Poland, were regularly questioned for the symptoms of COVID-19 and contact with an infected person. Patients that presented with COVID-19 symptoms or confirmed contact with an infected person were referred for the COVID-19 test. All patients with confirmed SARS-CoV-2 infection (n = 41) were included in the analysis. Medical records of the study group were analyzed. Patient condition was monitored in the outpatient clinic after recovery. In 26 subjects, additional examinations, including brain magnetic resonance imaging (MRI), electroneurography (ENG), electroencephalography (EEG), color duplex Doppler (CDD), visual evoked potentials (VEPs), brainstem auditory evoked potentials (BAEPs) and psychological assessment were performed following recovery. RESULTS: Only one patient required hospitalization during COVID-19 infection, whereas 87.80% of patients did not require treatment for COVID-19. In all patients, C-reactive protein (CRP) levels were below 10 mg/L. In 2.44% of patients, oxygen partial pressure was below 95%. In most MS patients, the results of further examinations after COVID-19 infection were similar to those prior to infection. Psychological assessment revealed that anxiety was found in 42.31% of patients. CONCLUSIONS: A mild course of COVID-19 in MS patients seems common despite disease-modifying drug treatment and disability. Self-isolation is recommended to reduce the number of infected patients. COVID-19 infection did not worsen the course of MS in most subjects. Patients with MS may require additional psychological support during the pandemic due to their susceptibility to anxiety.

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.

Multiple sclerosis patients and COVID-19.

Coronavirus disease 2019 (COVID-19) is now a major issue for all fields of medicine. Due to the higher mortality rate among patients with chronic diseases, it has also caused concern in patients with multiple sclerosis (MS), who in addition are often receiving immunosuppressive drugs. The aim of this article is to discuss what is currently known about the severity of COVID-19 in MS patients.

COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna) in patients with multiple sclerosis: a statement by a working group convened by the Section of Multiple Sclerosis and Neuroimmunology of the Polish Neurological Society.

A working group convened by the Section of Multiple Sclerosis and Neuroimmunology of the Polish Neurological Society has developed a statement with regard to the currently available mRNA vaccines (Pfizer-BioNTech and Moderna) preventing novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) infection, which causes Coronavirus disease 2019 (COVID-19), in patients with multiple sclerosis (MS). This statement has been based on the literature available as of 15 January, 2021. The guidance will be updated as new data emerges. All data regarding the above-mentioned vaccines comes from clinical trials which have been reviewed, published and approved by the regulatory authorities [1, 2]. In the current manuscript, whenever a SARS-CoV-2 vaccine is discussed, it refers to mRNA vaccines only.

Neurological symptoms as a clinical manifestation of coronavirus disease 2019: implications for internists.

Numerous experimental and clinical studies have proven that the new severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) has a tropism for the nervous system. The infection of the nervous system by SARS­CoV­2 can occur via the nasal route through trans­synaptic pathways. Coronaviruses can infect neurons and glial cells through angiotensin­converting enzyme 2 receptors or by endocytosis. The infection of the central nervous system accompanied by coronavirus disease 2019-related systemic inflammation leads to the impairment of the blood-brain barrier and triggers a neuroinflammatory response with reactive astrogliosis and microglial activation. In addition, brain stem cells are being damaged, which results in respiratory distress. Apart from typical symptoms of COVID­19 associated with the involvement of the respiratory system, neurological manifestations such as headache, dizziness, myalgia, anosmia, ageusia, encephalopathy, encephalitis, stroke, epileptic seizures, rhabdomyolysis, and Guillain-Barré syndrome are related to SARS­CoV­2 infection. In this review, we focused on the currently known neurological manifestations of COVID­19, which could be considered mainly in asymptomatic patients with COVID­19 and, if noted, may limit the transmission of coronavirus infection.

SARS-CoV-2/COVID-19 in multiple sclerosis patients receiving disease-modifying therapy.

At the end of 2019, the COVID-19 pandemic began, which at the time of writing continues to be a serious problem for many areas of medicine, including neurology. Since patients with multiple sclerosis (MS) often exhibit motor disability and receive disease-modifying therapy (DMT), which has an immunosuppressive effect, it is plausible that this will affect the susceptibility of MS patients to COVID-19, as well as the course of this disease. However, current data indicate that the use of DMT does not cause negative prognosis in COVID-19 sufferers, but the motor disability progression associated with MS does. In this study, we present the case reports of 4 patients with relapsing-remitting MS, who developed COVID-19, and despite the use of DMT the course of the disease was mild. Two patients were treated with dimethyl fumarate, one with Interferon ß1b and one with glatiramer acetate. One of the patients using dimethyl fumarate had lymphopenia. All patients had symptoms of COVID-19 from the nervous system, the most frequent being headache, which occurred in all patients. The aim of this article is to present a case series of four patients with MS and COVID-19, and to discuss the available literature on COVID-19 in patients with MS, with particular consideration of the impact of DMT.