Do Multiple Sclerosis and Neuromyelitis Optica Patients Have a Lower Chance of Developing Neurological Complications of COVID-19, Compared to Healthy People? The Role of ACE2

As COVID-19 spreads all around the world, it indicates various side effects and complications. Currently, we know that, this disease can affect other organs like brain. The growing number of neurological complications from this disease suggests that, the coronavirus is a neurotropic virus, and this neurotropicity has been attributed to the expression and presence of receptors of angiotensin-converting enzyme 2 (ACE2) in central nervous system (CNS). Unlike ACE itself, ACE2 converts angiotensin 2 to 1, and is present in lung alveolar epithelial cells. In this regard, the coronavirus is likely to use ACE2 as a receptor to enter and infect human cells. The virus causes disease in some other areas such as pancreas and colon with the same mechanism as that of ACE2 receptor. Moreover, the high presence of the corresponding receptor in the CNS has increased the likelihood of neurological involvement in this virus. The binding of the virus to this receptor (Figure 1), which is present in different areas of the brain such as the glial cells, neurons and astrocytes spreads the virus to the CNS and this induces a variety of neurological symptoms. One of the most important areas of the brain that causes high expressions of ACE and ACE2, angiotensinogen, and angiotensin II secretion in the CNS, is perivascular astrocytes. Neuromyelitis optica spectrum disorder (NMOSD) is an astrocytopathy in which a high rate of astrocyte destruction occurs. Some studies have also shown that, these perivascular astrocytes are largely eliminated in multiple sclerosis (MS), especially at chronic stages. This destruction could justify the studies, which have demonstrated the low levels of ACE2 in the cerebrospinal fluid of these patients. Matsushita et al. revealed that, angiotensin II, ACE, and ACE2 levels were lower in the cerebrospinal fluid of the patients with seropositive NMOSD compared to healthy individuals. Accordingly, the same was true for ACE2 levels in MS patients. Another study confirmed the low level of ACE2 concentration in the cerebrospinal fluid of the patients with MS. The destruction of astrocytes and low level of ACE2 concentration could theoretically predict the ACE2 receptor deficiency which might reduce the chance of entering the virus into the CNS, and consequently, decrease the neurological complications. This may suggest that, neurological complications are less likely to occur in the patients with NMOSD and MS in case of developing COVID-19. However, as with all diseases, it is not possible to simply predict the lower degree of neurological complications in these patients on the basis of one factor such as a lower expression of ACE2 in these patients. Thereafter, further investigations are required to shed light on how MS and NMOSD patients develop infectious diseases related to the CNS

Psychological Aspects of Neuroinflammatory Disorders in COVID-19 Era

Although the COVID-19 pandemic was initially manifested as a contagious respiratory infection, its other aspects quickly became apparent. Accordingly, the disease could affect various organs such as skin, digestive system, and the central nervous system. Apart from these diverse manifestations, it was rapidly cleared that the virus could potentially play a role in causing a wide range of autoimmune diseases. Moreover, various anthropological aspects of COVID-19 and its effects on human life were considered. In this regard, one of the important issues is its psychological effects, not only on the population of healthy people, but also on people suffering from underlying diseases. Inflammatory diseases of the central nervous system are included as one group of these diseases. Since these diseases can cause many psychological problems in patients, it is very important to pay attention to them during the COVID-19 pandemic. In the following section, the psychological aspects of COVID-19 in patients with neuroinflammatory diseases are described

Evaluation of the Incidence, Severity, and Mortality Rate of COVID-19 in Patients with Multiple Sclerosis Receiving Interferon β-1a

We enthusiastically read Payandemehr et al.’s study, which examined the effect of interferon β-1a (ReciGen, CinnaGen Co., Iran) on the severity of the disease in patients with COVID-19 and revealed that taking interferon β-1a (INF) significantly reduced the duration of hospitalization and the rate of mortality of hospitalized COVID-19 patients. INF is one of the main drugs in patients with relapsing-remitting multiple sclerosis (RRMS), and these patients mainly use this drug for a long time. We decided to examine whether the drug has an effect on the incidence rate of COVID-19 in MS patients and whether it affects the course of COVID-19 in case of infection. In November 2020, 75 RRMS patients treated with INF (ReciGen, CinnaGen Co., Iran) were evaluated for COVID-19. Fifty-seven and eighteen cases were female and male, respectively. Patients had a mean age of 36.9±7.2 years, disease duration of 7.0±4.4 years, and the INF use duration of 3.5±1.7 years. Of these 75 patients, only one patient (1.33%) tested positive for COVID-19. The patient was a 29-year-old female nurse working in the pediatric intensive care unit (ICU) and had been receiving INF for six years since the diagnosis of MS. She developed symptoms of cough, shortness of breath, lethargy, anorexia, constipation, and diarrhea in June 2020. The lung computed tomography (CT) scan indicated mild lung involvement, and the reverse transcription polymerase chain reaction (RT-PCR) test was positive for COVID-19. The patient continued her INF treatment, and the symptoms completely disappeared after five days. The patient did not require to be hospitalized during her COVID-19 infection. Therefore, the hospitalization rate due to COVID-19, hospitalization in the ICU, and mortality rate were zero in INF users. In a study by Sahraian et al. addressing 4647 MS patients revealed that the incidence of COVID-19 was 1.46%, which was similar to our findings concerning patients receiving INF. However, the hospitalization rate in the mentioned study was 25%, which was very different from that of our study. It should be noted that patients were taking a wide range of drugs in the mentioned study, and most of them were taking rituximab. Nevertheless, there was no relationship between the type of the administered drug and the chance of hospitalization in the mentioned study. Our findings suggest that there might be a link between the use of INF and non-hospitalization and lack of mortality in patients with MS infected by COVID-19. The obtained findings are in line with the results provided by Payandemehr et al.’s study. Although our study was observational and did not have a control group, it revealed that the INF administration might reduce the severity of the infection. However, the use of INF did not prevent COVID-19 infection. The positive effect of interferons on reducing the severity of COVID-19 has been indicated in other studies, as well. Considering its positive effect on COVID-19 and the fact that interferons have been used in the treatment of MS disease for many years, more attention should be devoted to administering this drug in patients with MS during COVID-19 as it can significantly reduce the risk of COVID-19 related complications

Could Fampridine Attenuate the Severity of COVID-19 in Patients with Multiple Sclerosis?

Since the onset of COVID-19 in December 2019, millions of people have been infected with SARS-CoV-2 across the world and many have died of the disease. Therefore, the search for any drug with a positive effect on the course of this disease is of great value. Fampridine is a drug widely used to improve gait disorders in patients with multiple sclerosis. The mentioned drug is a potassium channel blocker that increases the conduction of action potentials in damaged axons. However, it is not evident whether this drug can affect potassium channels on the surface of other cells. Some studies have revealed that potassium-blocking drugs can play a role in reducing the incidence or severity of infectious diseases. Hence, the question of whether fampridine could also have a protective effect on patients with MS in the face of COVID-19 should be attended to. The incidence and severity of COVID-19 in patients with MS receiving fampridine (Dalfyra®, Arvand Pharmed) were evaluated to address the mentioned question. In the present study conducted in November 2020, 117 MS patients receiving fampridine were tested for COVID-19. The majority of these patients (55.6%) were receiving rituximab. Of these 117 patients, nine were infected by the COVID-19 virus. Of these nine patients, five and four were female and male, respectively. Eight of the infected patients took rituximab, and one did not take any disease modulatory drug (DMD). One of these nine patients required to be hospitalized. She was a 40-year-old woman with MS disease duration of 3.5 years and was treated with rituximab. Her symptoms were manifested by fever, shortness of breath, and dry cough. The mentioned patient was hospitalized for three days due to the conditions associated with COVID-19. She did not need to be admitted to the intensive care unit (ICU) and was discharged with a good medical condition after three days. The incidence of COVID-19 in these patients was 7%, and the hospitalization rate was 11% in patients receiving fampridine. None of the patients with COVID-19 required hospitalization in the ICU, and no fatalities were reported. In a previous study conducted on 4,647 patients with MS in Iran, the incidence rate was reported to be 1.46% during the first wave of COVID-19 (May 2020). The incidence rate in our study was 7%, which was significantly higher than the percentage of the previous report. It should be noted that our study was conducted at the height of the second wave of COVID-19 in Iran, during which a much larger number of people were infected with COVID-19, according to official statistics. In the previous study, the hospitalization rate was 25%. However, fampridine users, despite being more infected, had a lower hospitalization rate (11%), which indicated a lower severity of the disease in these patients. The mentioned finding could be due to the possible protective effect of fampridine on the exacerbation of COVID-19 in these patients. This hypothesis requires further examination in more detail

Herpes simplex encephalitis after receiving Covid-19 vaccine; A case report

Shortly after the onset of the coronavirus pandemic, different vaccines were developed to combat it. The vaccines had different mechanisms and triggered cellular and humoral immune responses against the virus. In addition to their positive effects, various side effects have been reported for them. They rarely cause severe complications. They can also rarely trigger latent infections. The present case report presents a patient who developed herpes simplex encephalitis after receiving the second dose of the Covaxin (BBV152)

Association of Limb-Girdle muscular dystrophy with multiple sclerosis: A case report

Background: The association of limb-girdle muscular dystrophy (LGMD) with other neurological disorders is uncommon. Case presentation: We report a 25-year-old female with LGMD who suffered from slowly progressive proximal muscular weakness and atrophy since she was 12 years of age. The patient recently presented with acute loss of left side visual acuity. After evaluation, findings were suggestive of multiple sclerosis. Conclusions: This is the first report of LGMD in association with MS. The simultaneous occurrence of MS with myopathies may be incidental but there may be a genetic susceptibility for both diseases. This comorbidity may influence the treatment of MS

The Comparison of the Effectiveness of Cognitive-Behavioral Stress Management Training and Acceptance and Commitment Therapy on Interleukin 12 in patients with Multiple Sclerosis

Introduction: The levels of Biomarkers such as interleukin 12 (IL-12) are elevated in patients with Multiple Sclerosis (MS). The aim of the present study was to compare the effectiveness of Cognitive-Behavioral Stress Management (CBSM) training and Acceptance and Commitment Therapy (ACT) on IL-12 in Multiple Sclerosis (MS) patients. Methods: The present study was a quasi-experimental design with pretest-posttest and follow-up with control group. The statistical population included all female patients with Relapsing–Remitting MS who had referred to Multiple Sclerosis Research Center of Tehran University of Medical Sciences in Sina Hospital. 30 patients were selected by convenient sampling method and were replaced randomly into two experimental groups and one control group (each group included 10 patients). One of the experimental groups received the CBSM training and another experimental group received the ACT. To measure IL-12, the Enzyme-Linked Immunosorbent Assay (ELISA) was used. The data were analyzed using Analysis of Variance (ANOVA) with repeated measurement. Results: The results showed that ACT had no significant effect on IL-12 (p>0.05), but CBSM training significantly reduced IL-12 and these results remained in the follow-up period (p<0.001). Discussion: Relaxation techniques in CBSM can increase diaphragmatic breathing and decrease stress experience, including cortisol levels and stress. Subsequently, physiological symptoms reduce stress and thus affect the level of biomarkers like IL-12. Therefore, it can be useful in improving biological parameters in patients with MS