Infections In Multiple Sclerosis Patients Research Articles

COVID-19 Infection in Multiple Sclerosis Patients Treated with Rituximab Compared to Natalizumab and Healthy Controls: A Real-World Multicenter Study.

The impact of coronavirus disease 2019 (COVID-19) infection on patients with multiple sclerosis (MS) undergoing various immunomodulating therapies can vary. Individuals on B-cell therapy, such as rituximab, may be more susceptible to infection compared to those treated with natalizumab. The objective of this study was to determine the incidence and severity of COVID-19 infection in patients receiving rituximab, natalizumab, and healthy controls. This retrospective multicentric study included data derived from a centralized MS registry of four centers in South India. Data of patients on rituximab and natalizumab recruited between 2020 February and 2022 December were extracted from the registry and analyzed. The outcomes studied were the occurrence of COVID-19 infection, hospitalization, intensive care unit admission, death, post-COVID-19 relapses, and post-vaccine relapses. These outcomes were compared between the treatment groups and the matched controls. COVID-19 infection occurred in 49.1% (26/53) of those on rituximab, 19.2% (5/26) of those on natalizumab, and 11.5% (6/52) of healthy controls. In addition, 8/53 (15.1%) in the rituximab group and 1/26 (3.8%) in the natalizumab group were hospitalized. All 6/52 (11.5%) in the control group had mild infection, and none were hospitalized. No deaths occurred in any group. On statistical analysis, the occurrence of COVID-19 infection in the rituximab group was significantly higher when compared to natalizumab ( P = 0.0141) and healthy controls ( P < 0.001). Hospitalizations were significantly higher in the rituximab group when compared to healthy controls ( P < 0.006). MS patients treated with rituximab were more likely to experience COVID-19 infection compared to those treated with natalizumab and healthy controls. Hospitalization was more frequently seen in patients treated with rituximab compared to healthy controls.

Etiology, presentation and management of urinary tract infections in multiple sclerosis patients: A review of the current literature.

Urinary tract infections (UTIs) present a formidable challenge in the care of individuals affected by multiple sclerosis (MS). Lower urinary tract dysfunction is a prevalent issue among MS patients, predisposing them to an elevated risk of UTIs. When left untreated, UTIs can further exacerbate the already compromised quality of life in individuals with MS. The diagnosis and management of UTIs in MS patients necessitate a careful clinical evaluation. The objective of this review is to delineate preventive strategies and current and developing therapeutic approaches for preventing and treating UTIs associated with urinary dysfunction, catheterization, and upper urinary tract infections in patients with MS. Effectively addressing UTIs and urinary tract dysfunction in individuals with multiple sclerosis calls for a comprehensive, interdisciplinary approach.

Longitudinal increase of humoral responses after four SARS-CoV-2 vaccinations and infection in MS patients on fingolimod

Background: Humoral responses after SARS-CoV-2 vaccination are greatly impaired in multiple sclerosis (MS) patients on fingolimod. Effects of repeated vaccination and infections on long-term responses are unclear. Methods: Prospective study in 60 MS patients on fingolimod measuring humoral responses after up to four vaccinations and 8 months after fourth vaccination. Results: Anti-WH1 antibody titers increased with each additional vaccination. At long-term follow-up titers increased further and most patients developed new humoral responses against the BA.1 omicron variant. Conclusion: Repeated SARS-CoV-2 vaccinations boost humoral immunity and, probably together with SARS-CoV-2 infections, induce humoral responses on the long-term in almost all patients.

Interplay between age and disease-modifying treatments in influencing infection risk in multiple sclerosis.

Disease-modifying treatments (DMTs) can increase the risk of infections in multiple sclerosis (MS). Aged individuals are usually excluded from clinical trials, and there is uncertainty regarding safety of immunosuppressive DMTs in these patients. To investigate the association of DMTs, ageing and other clinical variables with risk of infections in MS patients. Prospective single-centre observational study collecting information on occurrence, type and grade of infections in patients followed at the MS centre, Lugano (Switzerland). Associations with infection risk were tested using multivariable Poisson and Cox regressions. A total of 503 patients were included (injectables/untreated, n = 127; orals, n = 139; monoclonal antibodies (MAB), n = 237) and 326 infections recorded over 12.6 (11.6-14.0) months. As compared to injectable DMTs/no treatment, MAB and oral DMTs were positively associated with infection incidence (IRR = 2.32, 95% confidence interval (CI) = 1.39-3.89, p = 0.001; IRR = 2.04, 95% CI = 1.19-3.49, p = 0.009, respectively). After excluding COVID-19, the effect of MAB was stronger among patients <50 years (IRR = 5.90, 95% CI = 2.80-12.45, p < 0.001) than >50 years (IRR = 1.95, 95% CI = 0.91-4.15, p = 0.084). Higher disability and male sex were the only variables associated with severe infections. Treatment with MAB and oral DMTs is associated with higher incidence of infections, with a stronger effect in young MS patients. Disability appears the main predictor of severe infections regardless of treatment.

Associations between Toxoplasma gondii Infection and Multiple Sclerosis: A Case-Control Seroprevalence Study.

Currently, there are conflicting reports on the associations between Toxoplasma gondii infection and multiple sclerosis (MS) in humans. In the present study, a case-control study was carried out to assess associations between seropositivity to T. gondii infection and MS. This case-control study was carried out on 200 MS patients (cases) attended in Sina Hospital affiliated to Tehran University of Medical Sciences, Tehran, Iran, and 200 healthy subjects from the general population of the same city, March to July 2017. Blood samples were collected from individuals and were examined using Enzyme-linked immunosorbent assay (ELISA) for the presence of T. gondii IgG antibodies and the IgG-positive samples were further analyzed for specific anti-T. gondii IgM. The overall seroprevalence of anti-T. gondii IgG was 44.2% (177/400) in 121 (60.5%) sera of the 200 MS patients (cases) and 56 (28.0%) sera of the 200 controls (OR = 3.94; 95% CI: 2.59-5.99; P < 0.001). Seroprevalence of T. gondii infection in MS patients increased significantly with increasing of age (P < 0.001). In the control group, no statistically significant differences were seen between the seroprevalence of T. gondii infection in various age groups (P = 0.858). Moreover, no statistically significant relationships were reported between the seropositivity to T. gondii and the sex for the cases and controls (P>0.05). Anti-T. gondii IgM antibodies were not detected in anti-T. gondii IgG positive patients. T. gondii infection might be a probability risk factor for MS. However, further studies are necessary to describe clearly the roles of T. gondii infection in MS.

Immune responses following COVID-19 infection in multiple sclerosis patients using immunomodulatory therapy.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has quickly become a global pandemic. Most multiple sclerosis (MS) patients use disease-modifying treatments (DMTs), such as immunomodulators or immunosuppressants. By targeting different types of immune cells, DMTs affect cellular and/or humoral immunity. The potential effects of DMTs on the long-term immune response to COVID-19 is not fully known. Between 16.04.2020 and 15.07.2020, a total of 34 people, 17 of whom were diagnosed with MS according to the 2010 McDonald diagnostic criteria and a control group of 17 individuals who did not have a known systemic disease who were matched according to age, gender, and COVID-19 disease severity, where all received COVID-19 diagnosis with SARS-CoV-2 PCR positivity in nasopharyngeal swab test and immune responses were measured (SARS-CoV-2 IgM and IgG antibody levels COVID 19 ELISA kit), were included in our study. Demographic data of MS patients and the control group, SARS-CoV-2 immune responses, antibody titers and disease year of MS patients, EDSS scores, disease type, and disease duration were determined. All patients were symptomatic for COVID-19. COVID-19 disease severity was divided into three groups as mild, moderate, and severe according to the clinical condition of the patient. Demographic data of MS patients and the control group, SARS-CoV-2 immune responses, antibody titers and disease year of MS patients, EDSS scores, disease type, and disease duration were determined. All patients were symptomatic for COVID-19. COVID-19 disease severity was divided into three groups as mild, moderate, and severe according to the clinical condition of the patient. According to our study results, IgG-type long-term immune responses were lower in MS patients using DMTs than in the healthy population. We hope that our study will provide insight into the COVID-19 vaccine immune responses.

SARS-CoV-2 infection in multiple sclerosis patients: interaction with treatments, adjuvant therapies, and vaccines against COVID-19.

The SARS-CoV-2 pandemic has raised particular concern for people with Multiple Sclerosis, as these people are believed to be at increased risk of infection, especially those being treated with disease-modifying therapies. Therefore, the objective of this review was to describe how COVID-19 affects people who suffer from Multiple Sclerosis, evaluating the risk they have of suffering an infection by this virus, according to the therapy to which they are subjected as well as the immune response of these patients both to infection and vaccines and the neurological consequences that the virus can have in the long term. The results regarding the increased risk of infection due to treatment are contradictory. B-cell depletion therapies may cause patients to have a lower probability of generating a detectable neutralizing antibody titer. However, more studies are needed to help understand how this virus works, paying special attention to long COVID and the neurological symptoms that it causes.

Risk of serious infections in multiple sclerosis patients by disease course and disability status: Results from a Swedish register-based study

Background and objectivesSerious infections are an emerging concern with increasing use of potent immunomodulation in multiple sclerosis (MS), but the extent to which MS disease features influence infectious susceptibility is poorly characterized. The objective of this study was to assess the associations of MS disease course and disability status with risk of serious infections. MethodsA cohort of 8660 MS patients was individually matched on age, sex and region of residence with 86,600 people without MS from the general population using national registers in Sweden. The study period was from 1996 to 2012, with follow-up until December 31, 2014. The main outcomes were infection as the underlying or contributory cause of death or infection-related hospital admission identified in the Cause of Death and Patient registers. MS disease course (relapsing-remitting or progressive disease) and Expanded Disability Status Scale (EDSS) score (six and over or below six) were extracted from the MS Register Hazard ratios (HRs) for any serious infection were estimated using flexible parametric models. ResultsDuring a median follow-up of 9.6 years (interquartile range = 5.5–13.5 years), 1337 MS patients experienced a serious infection. Compared with individually matched people without MS, risk of serious infection was greater for progressive disease (HR = 3.80; 95% CI 3.52: 4.09) than relapsing-remitting disease (HR = 1.77; 95% CI: 1.62:1.93). A similar pattern of risk was seen for dichotomised EDSS score (HR = 4.26; 95% CI 3.87: 4.70 for EDSS 6.0–9.5 and HR = 1.30; 95% CI 1.1853: 1.43 for EDSS 0.0–5.5). Overall, associations with greater disability did not notably differ by immunomodulatory therapy use, but associations with lower disability were more pronounced in patients receiving these therapies. ConclusionsDisease course or EDSS score (which may be more readily available than MS course in some patients) should be considered in individual management and monitoring of MS patients, including assessing benefit-risk of therapies that influence general immune function.

Risks of Minor and Severe Infections in Multiple Sclerosis Patients Treated with Long-term B-cell Depletion (P13-4.011)

Risks of Minor and Severe Infections in Multiple Sclerosis Patients Treated with Long-term B-cell Depletion (P13-4.011)

Vaccination Coverage against Tetanus, Diphtheria, Pertussis and Poliomyelitis and Validity of Self-Reported Vaccination Status in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic immune-mediated disease with a neurodegenerative component of the central nervous system. Immunomodulatory therapy can increase the risk of infection, which is a particular risk for MS patients. Therefore, a complete vaccination status is of utmost importance as protection against vaccine-preventable infectious diseases. Our aim was to investigate the vaccination status, vaccination card knowledge and the vaccination behavior of MS patients with regard to vaccinations against tetanus, diphtheria, pertussis and poliomyelitis. Three hundred twenty-seven patients with MS were evaluated by anamnesis, clinical examination, structured interview and vaccination card control in this two-center study. Based on the recommendations of the Robert Koch Institute, we assessed the completeness of the vaccination status of the examined vaccinations. Furthermore, a comparative analysis of patients with complete/incomplete or correctly/wrongly self-reported vaccination status was performed. In the cohort analyzed, the vaccination coverage was 79.5% for tetanus, 79.2% for diphtheria, 74.8% for pertussis and 84.8% for poliomyelitis. The assumed vaccination status was higher for tetanus (86.5%) and lower for diphtheria (69.4%), pertussis (61.2%) and poliomyelitis (75.9%). Patients who were unvaccinated or only partially vaccinated against tetanus had received vaccination advice from a physician less often in the past year (13.4 vs. 36.9%, p < 0.001) and had no one to check the vaccination card more often (35.8 vs. 12.3%, p < 0.001). High sensitivity (93.7%) and low specificity (30.3%) were determined regarding the validity of self-reported tetanus vaccination status. Patients with a correctly reported tetanus vaccination status were more likely to have their vaccination card checked by a physician than those who overestimated or underestimated their vaccination status (76.7 vs. 63.0/43.8%, p = 0.002). Similar findings were seen with regard to diphtheria, pertussis and poliomyelitis vaccination. Patients without a regular vaccination card control (17.1%) were more likely to be male (44.6 vs. 29.4%, p = 0.037), had fewer siblings on average (1.1 vs. 1.6, p = 0.016), dealt less frequently with the issue of vaccination in the past year (32.1 vs. 69.3%, p < 0.001) and more frequently had the wish to receive vaccination advice (48.2 vs. 34.4%, p = 0.030) than patients in whom the vaccination card was checked regularly by a physician. To minimize the risk of infection in MS patients, treating physicians should provide regular vaccination counseling and perform vaccination card controls, as these factors are associated with a higher vaccination coverage and a higher validity of self-reported vaccination statuses.

Cellular and Humoral Immunity to SARS-CoV-2 Infection in Multiple Sclerosis Patients on Ocrelizumab and Other Disease-Modifying Therapies: A Multi-Ethnic Observational Study.

ObjectiveThe objective of this study was to determine the impact of multiple sclerosis (MS) disease‐modifying therapies (DMTs) on the development of cellular and humoral immunity to severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection.MethodsPatients with MS aged 18 to 60 years were evaluated for anti‐nucleocapsid and anti‐Spike receptor‐binding domain (RBD) antibody with electro‐chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N‐terminal domain with multiepitope bead‐based immunoassays (MBI); live virus immunofluorescence‐based microneutralization assay; T‐cell responses to SARS‐CoV‐2 Spike using TruCulture enzyme‐linked immunosorbent assay (ELISA); and IL‐2 and IFNγ ELISpot assays. Assay results were compared by DMT class. Spearman correlation and multivariate analyses were performed to examine associations between immunologic responses and infection severity.ResultsBetween January 6, 2021, and July 21, 2021, 389 patients with MS were recruited (mean age 40.3 years; 74% women; 62% non‐White). Most common DMTs were ocrelizumab (OCR)—40%; natalizumab —17%, Sphingosine 1‐phosphate receptor (S1P) modulators −12%; and 15% untreated. One hundred seventy‐seven patients (46%) had laboratory evidence of SARS‐CoV‐2 infection; 130 had symptomatic infection, and 47 were asymptomatic. Antibody responses were markedly attenuated in OCR compared with other groups (p ≤0.0001). T‐cell responses (IFNγ) were decreased in S1P (p = 0.03), increased in natalizumab (p <0.001), and similar in other DMTs, including OCR. Cellular and humoral responses were moderately correlated in both OCR (r = 0.45, p = 0.0002) and non‐OCR (r = 0.64, p <0.0001). Immune responses did not differ by race/ethnicity. Coronavirus disease 2019 (COVID‐19) clinical course was mostly non‐severe and similar across DMTs; 7% (9/130) were hospitalized.InterpretationDMTs had differential effects on humoral and cellular immune responses to SARS‐CoV‐2 infection. Immune responses did not correlate with COVID‐19 clinical severity in this relatively young and nondisabled group of patients with MS. ANN NEUROL 2022;91:782–795

A one year follow of patients with multiple sclerosis during COVID-19 pandemic: A cross-sectional study in Qom province, Iran

BackgroundIn the current COVID-19 pandemic, Multiple Sclerosis (MS) patients represent a population of particular interest as they might be at higher risk of COVID-19 infection and it's complications. The present study aimed to investigate a one year follow up of patients with MS during the COVID-19 pandemic, in Qom province, Iran. MethodsThis study was performed at the MS Clinic of Beheshti Hospital from June 1, 2020 to November 1, 2021. 202 patients with a diagnosis of MS and negative self-reported history of COVID-19 at the beginning of the pandemic, were enrolled. First, the demographic characteristics of patients were collected. Second, the patients underwent serological testing for anti-SARS-CoV-2 IgG antibodies. Then, a year later, they were revalauted and asked about the occurrence of clinical relapse leading to hospitalization, disease progression, DMT profile, COVID-19 vaccination, and history of COVID-19 infection. We considered six weeks after COVID-19 regarding relapse occurrence. Eventually, statistical analysis was carried out by using SPSS 26.0 ResultsOf 202 patients, 26 patients (12.87%) had initially a positive index antibody result. During the follow-up periods, 25 patients (12.37%) were infected with COVID-19 which was mainly mild (74.8%), and significantly lower than general population. 118 patients (58.41%) were vaccinated for COVID-19 which reduced the risk of COVID-19 development (P<001). Except a case of myelitis associated with vaccination, no serious adverse event was reported. Additionally, only one patient developed MS relapse following COVID-19 infection. Except clinical relapse (P = 0.001), other demographic and MS characteristics, and DMT type were not associated with COVID-19. In terms of MS course, 12 patients (5.94%) discontinued their DMTs regardless of the DMT adverse events or treatment failure. 41 patients (20.3%) experienced a clinical relapse, of whom 12 were escalated to a second line DMT. Further, 27 patients (13.4%) noted a history of worsening disability which mainly occurred after COIVD-19 infection. ConclusionThe present study showed a significant lower incidence of COVID-19 infection in MS patients. Except for clinical relapse, other demographic and MS characteristics, and DMT type were not associated with COVID-19 infection. In addition, COVID-19 vaccination reduced the risk of COVID-19 development, and the prognosis was favorable in the majority of MS patients.

Herpesvirus Infections in KIR2DL2-Positive Multiple Sclerosis Patients: Mechanisms Triggering Autoimmunity.

In multiple sclerosis (MS), there is a possible relationship with viral infection, evidenced by clinical evidence of an implication of infectious events with disease onset and/or relapse. The aim of this research is to study how human herpesvirus (HHVs) infections might dysregulate the innate immune system and impact autoimmune responses in MS. We analyzed 100 MS relapsing remitting patients, in the remission phase, 100 healthy controls and 100 subjects with other inflammatory neurological diseases (OIND) (neuro-lupus) for their immune response to HHV infection. We evaluated NK cell response, levels of HHVs DNA, IgG and pro- and anti-inflammatory cytokines. The results demonstrated that the presence of KIR2DL2 expression on NK cells increased the susceptibility of MS patients to HHV infections. We showed an increased susceptibility mainly to EBV and HHV-6 infections in MS patients carrying the KIR2DL2 receptor and HLA-C1 ligand. The highest HHV-6 viral load was observed in MS patients, with an increased percentage of subjects positive for IgG against HHV-6 in KIR2DL2-positive MS and OIND subjects compared to controls. MS and OIND patients showed the highest levels of IL-8, IL-12p70, IL-10 and TNF-alpha in comparison with control subjects. Interestingly, MS and OIND patients showed similar levels of IL-8, while MS patients presented higher IL-12p70, TNF-alpha and IL-10 levels in comparison with OIND patients. We can hypothesize that HHVs’ reactivation, by inducing immune activation via also molecular mimicry, may have the ability to induce autoimmunity and cause tissue damage and consequent MS lesion development.

Validation of algorithms for identifying outpatient infections in MS patients using electronic medical records

Background Our multiple sclerosis (MS) stakeholder groups expressed concerns about whether MS disease-modifying therapies (DMTs) increase the risk of specific outpatient infections. Validated methods for identifying the risk of these selected outpatient infections in the general population either do not exist, exclude the clinically important possibility of recurrent infections, or are inaccurate, largely because existing studies relied primarily on International Classification of Diseases (ICD) codes to identify infectious outcomes. Additionally, no studies have validated methods among the MS population, where some MS symptoms can be mistaken for infections (e.g., urinary tract infections (UTIs)).Objective To utilize multiple data elements in the electronic health record (EHR) to improve accurate identification of selected outpatient infections in an MS cohort and general population controls.Methods We searched Kaiser Permanente Southern California's EHR based on ICD-9/10 codes for specified outpatient infections from 1/1/2008-12/31/2018 among our MS cohort (n=6000) and 5:1 general population controls matched on age, sex, and race/ethnicity (n=30,010). Random sample chart abstractions from each group were used to identify common coding errors for outpatient pneumonia, upper and lower respiratory tract infection, UTIs, herpetic infections (herpes zoster (HZ), herpes simplex virus (HSV)), fungal infections, otitis media, cellulitis, and influenza. This information was used to define discrete infectious episodes and to identify the algorithm with the highest positive predictive value (PPV) after supplementing the ICD-coded episodes with radiology, laboratory and/or pharmacy data.Results PPVs relying on ICD codes alone were inaccurate, particularly for identifying recurrent herpetic infections (HZ (42%) and HSV (60%)), UTIs (42%) and outpatient pneumonia (20%) in MS patients. Defining and validating episodes improved the PPVs for all the selected infections. The final algorithms’ PPVs were 80-100% in MS and 75-100% in the general population, after including dispensed treatments (UTI, herpetic infections and yeast vaginitis), timing of dispensed treatments (UTI, herpetic infections and yeast vaginitis), removal of prophylactic antiviral use (herpetic infections), and inclusion of selected laboratory (UTIs) and imaging results (pneumonia). The only exception was outpatient pneumonia, where PPVs improved but remained ≤70%. There were no significant differences in the PPVs for the final algorithms between the MS and general population.Conclusions Provided herein are accurate and validated algorithms that can be used to improve our understanding of how the risk of recurrent outpatient infections are influenced by MS treatments, MS-related disability, and co-morbidities. Findings from such studies will be important in helping patients and clinicians engage in shared decision-making and in developing strategies to mitigate risks of recurrent infections.

Prognostic factors related to the risk of COVID-19 infection in MS patients

It is still debated whether Multiple Sclerosis (MS) patients are at high-risk of COVID-19 because of their life style, disease- or treatments-associated immune alterations. We compared features of MS patients with COVID-19 infection (MS-COVID) to those of residency-, age-, sex- and treatment-matched MS controls (MS-NCOVID). Moreover, the severity of COVID-19 infection was assessed in MS-COVID patients and their cohabitants.

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

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. 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. 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. 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 and COVID‐19: How could therapeutic scenarios change during the pandemic?

We read with great interest the review by Rostami Mansoor and Ghasemi-Kasman entitled "Impact of disease-modifying drugs on the severity of COVID-19 infection in multiple sclerosis patients" on your journal. This article is protected by copyright. All rights reserved.

Nasolacrimal transition time in patients with multiple sclerosis.

To measure the duration of nasolacrimal transition in patients with Multiple Sclerosis (MS), to compare the findings with the healthy population and to investigate the relationship between MS-related disability and nasolacrimal transition time. A total of 73 individuals including 37 patients with relapsing-remitting MS and 36 healthy volunteers were included in the study. In both groups the nasolacrimal transition time was measured using flurosein drops. The degree of disability of MS patients was calculated according to the Expanded Disability Status Scale (EDSS). There was a significant difference between MS patients and control group in terms of the median value of nasolacrimal transition time in (240s (min: 85, max: 724) and 58.5s (min: 21, max: 428), respectively) (p < 0.001). A positive correlation was found between EDSS scores and nasolacrimal transition time of MS patients (r = 0.384, p = 0.019). This study showed that nasolacrimal transition time is prolonged in MS patients and there is a relationship between the degree of MS-related disability and the nasolacrimal transition time. This is the first study in the literature on this subject and the results of our study have the potential to shed light on the causes of common infections in MS patients. Long-term prospective studies are needed to further investigate the relationship between prolonged nasolacrimal transition and infections in MS patients.

Outcome of COVID-19 infection in multiple sclerosis patients receiving disease-modifying therapies.

Background:With the spread of COVID-19, treatment of diseases such as multiple sclerosis (MS) should be resumed with caution due to the disease-modifying therapies (DMTs) used in this subset of patients and the immunoregulatory effects of these drugs. We aim to assess the outcome of COVID-19 infection in MS patients receiving DMTs.Materials and Methods:This is a cross-sectional study involving 45 COVID-19-infected patients previously diagnosed with MS. The data regarding their MS status and the type of DMT taken by the patients were extracted from the Isfahan MS Institute registry and were summarized. Diagnosis of MS was based on the 2017 McDonald Criteria, and the diagnosis of COVID-19 was based on computed tomography scan and polymerase chain reaction of nasopharyngeal swabs.Results:Out of the 45 MS patients infected with COVID-19, 5 had unfavorable outcomes. Two patients deceased and the other three had persistent respiratory complications on the 4-week follow-up visit. Hypertension, diabetes, seizures, and rheumatoid arthritis were among the comorbidities that the patients reported. Both patients who died received rituximab as part of their MS treatment. All other patients recovered completely.Conclusion:Each different drug category may possess a distinct risk for infection, therefore until robust evidence are available, the safest drug should be utilized or the therapy should be postponed, if possible, to minimize patient risk. Disease-modifying therapy use in MS patients should be cautiously applied as their effect on COVID-19 infection prognosis is not yet studied.

Impact of disease-modifying drugs on the severity of COVID-19 infection in multiple sclerosis patients.

Recent evidence suggested that neurological manifestations occur in patients with a severe form of coronavirus disease (COVID‐19). On the basis of this issue, neurologists are very concerned about patients with neurological disorders, especially multiple sclerosis (MS), as consumers of immunosuppressive or immune‐modulating drugs. Therefore, the administration of proper disease‐modifying therapies (DMTs) in MS patients is critical during the pandemic status. On the one hand, both the autoimmune diseases and immunosuppressive drugs increase the risk of infection due to impairment in the immune system, and on the other hand, postponing of MS treatment has serious consequences on the central nervous system. In the present study, we discussed recent literature about the effect of DMTs administration on the severity of COVID‐19 in the MS patients. Overall, it seems that DMTs do not provoke the COVID‐19 infection in the MS patients by declining immune responses and cytokine storm. However, as a precaution, the supervision of a neurologist is highly recommended.