Sars-CoV2 infection in pregnant women with multiple sclerosis.

BACKGROUND: In the general population, maternal SARS-CoV-2 infection during pregnancy is associated with worse maternal outcomes; however, only one study so far has evaluated COVID-19 clinical outcomes in pregnant and postpartum women with multiple sclerosis, showing no higher risk for poor COVID-19 outcomes in these patients. OBJECTIVE: In this multicenter study, we aimed to evaluate COVID-19 clinical outcomes in pregnant patients with multiple sclerosis. METHODS: We recruited 85 pregnant patients with multiple sclerosis who contracted COVID-19 after conception and were prospectively followed-up in Italian and Turkish Centers, in the period 2020-2022. A control group of 1354 women was extracted from the database of the Multiple Sclerosis and COVID-19 (MuSC-19). Univariate and subsequent logistic regression models were fitted to search for risk factors associated with severe COVID-19 course (at least one outcome among hospitalization, intensive care unit [ICU] admission and death). RESULTS: In the multivariable analysis, independent predictors of severe COVID-19 were age, body mass index ⩾ 30, treatment with anti-CD20 and recent use of methylprednisolone. Vaccination before infection was a protective factor. Vaccination before infection was a protective factor. Pregnancy was not a risk nor a protective factor for severe COVID-19 course. CONCLUSION: Our data show no significant increase of severe COVID-19 outcomes in patients with multiple sclerosis who contracted the infection during pregnancy.

mRNA versus inactivated virus COVID-19 vaccines in multiple sclerosis: Humoral responses and protectivity-Does it matter?

BACKGROUND: COVID-19 vaccines are recommended for people with multiple sclerosis (pwMS). Adequate humoral responses are obtained in pwMS receiving disease-modifying therapies (DMTs) after vaccination, with the exception of those receiving B-cell-depleting therapies and non-selective S1P modulators. However, most of the reported studies on the immunity of COVID-19 vaccinations have included mRNA vaccines, and information on inactivated virus vaccine responses, long-term protectivity, and comparative studies with mRNA vaccines are very limited. Here, we aimed to investigate the association between humoral vaccine responses and COVID-19 infection outcomes following mRNA and inactivated virus vaccines in a large national cohort of pwMS receiving DMTs. METHODS: This is a cross-sectional and prospective multicenter study on COVID-19-vaccinated pwMS. Blood samples of pwMS with or without DMTs and healthy controls were collected after two doses of inactivated virus (Sinovac) or mRNA (Pfizer-BioNTech) vaccines. PwMS were sub-grouped according to the mode of action of the DMTs that they were receiving. SARS-CoV-2 IgG titers were evaluated by chemiluminescent microparticle immunoassay. A representative sample of this study cohort was followed up for a year. COVID-19 infection status and clinical outcomes were compared between the mRNA and inactivated virus groups as well as among pwMS subgroups. RESULTS: A total of 1484 pwMS (1387 treated, 97 untreated) and 185 healthy controls were included in the analyses (male/female: 544/1125). Of those, 852 (51.05%) received BioNTech, and 817 (48.95%) received Sinovac. mRNA and inactivated virus vaccines result in similar seropositivity; however, the BioNTech vaccination group had significantly higher antibody titers (7.175±10.074) compared with the Sinovac vaccination group (823±1.774) (p<0.001). PwMS under ocrelizumab, fingolimod, and cladribine treatments had lower humoral responses compared with the healthy controls in both vaccine types. After a mean of 327±16 days, 246/704 (34.9%) of pwMS who were contacted had COVID-19 infection, among whom 83% had asymptomatic or mild disease. There was no significant difference in infection rates of COVID-19 between participants vaccinated with BioNTech or Sinovac vaccines. Furthermore, regression analyses show that no association was found regarding age, sex, Expanded Disability Status Scale score (EDSS), the number of vaccination, DMT type, or humoral antibody responses with COVID-19 infection rate and disease severity, except BMI Body mass index (BMI). CONCLUSION: mRNA and inactivated virus vaccines had similar seropositivity; however, mRNA vaccines appeared to be more effective in producing SARS-CoV-2 IgG antibodies. B-cell-depleting therapies fingolimod and cladribine were associated with attenuated antibody titer. mRNA and inactive virus vaccines had equal long-term protectivity against COVID-19 infection regardless of the antibody status.

Gender and COVID-19 related fear and anxiety: A meta-analysis.

Studies conducted during the pandemic revealed strong associations between gender and COVID-19 related fear and anxiety. Females perceive coronavirus as a greater threat to personal health and population than males. The aim of the current meta-analysis is to estimate gender difference in COVID-19 related fear and anxiety. The second purpose of this study is to clarify the role of potential moderators in COVID-19 fear and anxiety. For these reasons, studies published between March 2020 and October 2021 were searched in various databases (Web of Science, SCOPUS, PubMed, and Google Scholar). In total, 315 studies met the inclusion criteria, and 60 studies for COVID-19 related fear and 23 studies for COVID-19 related anxiety were included in the current study. Cohen's d effect size values were calculated based on these individual studies showing the difference between males and females in terms of COVID-19 related fear and anxiety. Results revealed that gender has a moderate and statistically significant effect on COVID-19 related fear (ES = 0.307) and anxiety (ES = 0.316) in favor of females. Moderator analyses showed that continent variable was a statistically significant moderator of gender difference in COVID-19 related fear and anxiety. The highest effect size of gender differences in COVID-related fear and anxiety were obtained from the studies conducted in Europe. However, other moderators (the average age of sample, culture, timing, and population) were not statistically significant. Although this meta-analysis has a few limitations, the findings showed that COVID-19 outbreak negatively affected females more.

The Socioeconomic and Psychological Impact of the COVID-19 Pandemic on People with Multiple Sclerosis in Turkey.

Introduction: Various restrictions due to the coronavirus infection have affected working life globally. People with multiple sclerosis (pwMS) have several difficulties in social life, patient follow-up, and receiving treatments. In this study, we aimed to evaluate the experiences of pwMS during the COVID-19 pandemic. Method: We developed a 50-question survey aiming to determine fears, anxieties, and the problems experienced by patients regarding their diseases and social lives during the COVID-19 pandemic. The questionnaire was released online via the Turkish MS Society website, local MS societies websites, and social media accounts. Only the answers of the patients who filled out the questionnaire completely were evaluated. Results: In total, 6008 patients took the survey, and 3255 of them completed the questionnaire. Among all, 378 patients (11.6%) were positive for COVID-19. The most common COVID-19-related symptom was fatigue (48.4%). The routine medical follow-up was interrupted in 61.4% and the medication was discontinued in 14% of the patients. Approximately 25% of the patients reported different symptoms related to relapse activity. The main concern of the patients related to the COVID-19 pandemic was the disruption of the health of the ones they loved. Among all the patients, 4.4% lost their jobs. Conclusion: Our data showed that the COVID-19 pandemic strongly affected the working lives of pwMS. Also, the pandemic changed the attitudes of patients and neurologists. Therefore, the long-term effects of the COVID-19 pandemic on disease approach, patient follow-up, social conditions, and working life should be monitored.

A multiparametric score for assessing the individual risk of severe Covid-19 among patients with Multiple Sclerosis.

BACKGROUND: Many risk factors for the development of severe forms of Covid-19 have been identified, some applying to the general population and others specific to Multiple Sclerosis (MS) patients. However, a score for quantifying the individual risk of severe Covid-19 in patients with MS is not available. The aim of this study was to construct such score and to evaluate its performance. METHODS: Data on patients with MS infected with Covid-19 in Italy, Turkey and South America were extracted from the Musc-19 platform. After imputation of missing values, data were separated into training data set (70%) and validation data set (30%). Univariable logistic regression models were performed in the training dataset to identify the main risk factors to be included in the multivariable logistic regression analyses. To select the most relevant variables we applied three different approaches: (1) multivariable stepwise, (2) Lasso regression, (3) Bayesian model averaging. Three scores were defined as the linear combination of the coefficients estimated in the models multiplied by the corresponding value of the variables and higher scores were associated to higher risk of severe Covid-19 course. The performances of the three scores were compared in the validation dataset based on the area under the ROC curve (AUC) and an optimal cut-off was calculated in the training dataset for the score with the best performance. The probability of showing a severe Covid-19 course was calculated based on the score with the best performance. RESULTS: 3852 patients were included in the study (2696 in the training dataset and 1156 in the validation data set). 17% of the patients required hospitalization and risk factors for severe Covid-19 course were older age, male sex, living in Turkey or South America instead of living in Italy, presence of comorbidities, progressive MS, longer disease duration, higher Expanded Disability Status Scale, Methylprednisolone use and anti-CD20 treatment. The score with the best performance was the one derived using the Lasso selection approach (AUC= 0.72) and it was built with the following variables: age, sex, country, BMI, presence of comorbidities, EDSS, methylprednisolone use, treatment. An excel spreadsheet to calculate the score and the probability of severe Covid-19 is available at the following link: https://osf.io/ac47u/?view_only=691814d57b564a34b3596e4fcdcf8580. CONCLUSIONS: The originality of this study consists in building a useful tool to quantify the individual risk for Covid-19 severity based on patient's characteristics. Due to the modest predictive ability and to the need of external validation, this tool is not ready for being fully used in clinical practice to make important decisions or interventions. However, it can be used as an additional instrument to identify high-risk patients and persuade them to take important measures to prevent Covid-19 infection (i.e. getting vaccinated against Covid-19, adhering to social distancing, and using of personal protection equipment).

Gender and COVID-19 related fear and anxiety: A meta-analysis

Studies conducted during the pandemic revealed strong associations between gender and COVID-19 related fear and anxiety. Females perceive coronavirus as a greater threat to personal health and population than males. The aim of the current meta-analysis is to estimate gender difference in COVID-19 related fear and anxiety. The second purpose of this study is to clarify the role of potential moderators in COVID-19 fear and anxiety. For these reasons, studies published between March 2020 and October 2021 were searched in various databases (Web of Science, SCOPUS, PubMed, and Google Scholar). In total, 315 studies met the inclusion criteria, and 60 studies for COVID-19 related fear and 23 studies for COVID-19 related anxiety were included in the current study. Cohen's d effect size values were calculated based on these individual studies showing the difference between males and females in terms of COVID-19 related fear and anxiety. Results revealed that gender has a moderate and significant effect on COVID-19 related fear (ES = 0.307) and anxiety (ES = 0.316) in favor of females. Moderator analyses showed that continent variable was a significant moderator of gender difference in COVID-19 related fear and anxiety. The highest effect size of gender differences in COVID-related fear and anxiety were obtained from the studies conducted in Europe. However, other moderators (the average age of sample, culture, timing, and population) were not statistically significant. Although this meta-analysis has a few limitations, the findings showed that COVID-19 outbreak negatively affected females more.

The Turkish experience of COVID-19 infection in people with NMOSD and MOGAD: A milder course?

BACKGROUND: COVID-19 is a multisystemic infection with variables consequences depending on individual and comorbid conditions. The course and outcomes of COVID-19 during neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are not clearly known. OBJECTIVE/METHODS: The aim of this study was to examine the features and outcomes of COVID-19 infection in NMOSD and MOGAD patients. The patients' demographic and clinical factors, disease modifying treatment (DMT) used and disease information of COVID-19 infection were recorded. Conditions leading to hospitalization and severe exposure to COVID-19 infection were also analyzed. RESULTS: The study included 63 patients from 25 centers. Thirty-two patients (50.8%) belong to AQP-4 seropositive group, 13 (20.6%) and 18 (28.6%) were in MOG-positive and double-seronegative groups, respectively. Risk factors for severe COVID-19 infection and hospitalization were advanced age, high disability level and the presence of comorbid disease. Disease severity was found to be high in double-seronegative NMOSD and low in MOGAD patients. No statistically significant effect of DMTs on disease severity and hospitalization was found. CONCLUSION: In NMOSD and MOGAD patients, advanced age, high disability and presence of comorbid disease pose risks for severe COVID-19 infection. There was no direct significant effect of DMTs for COVID-19 infection.

SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study.

BACKGROUND: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. OBJECTIVE: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. METHODS: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. RESULTS: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). CONCLUSION: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.