The effect of air pollution on COVID-19 severity in a sample of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID-19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID-19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID-19 severity amongst PwMS. METHODS: Data were retrieved from an Italian web-based platform (MuSC-19) which includes PwMS with COVID-19. PM2.5 2016-2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID-19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID-19 severity. RESULTS: In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID-19 course (odds ratio 1.90; p = 0.009). CONCLUSIONS: Even if several other factors explain the unfavourable course of COVID-19 in PwMS, the role of air pollutants must be considered and further investigated.

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context.

BACKGROUND AND OBJECTIVES: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. METHODS: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). RESULTS: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). DISCUSSION: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon.

Monoclonal antibodies for mild-to-moderate COVID-19 in multiple sclerosis: A case series.

We reported on five people with MS, using immunodepleting disease modifying treatments (anti-CD20 monoclonal antibodies and sphingosine-one-phosphate modulators) and with reduced COVID-19 vaccine response, who had mild-to-moderate symptomatic COVID-19, and were treated with anti-SARS-CoV-2 monoclonal antibodies. In particular, we showed the possibility to use monoclonal antibodies to speed-up recovery from COVID-19 in MS, in the absence of any COVID-19 residuals or MS changes (e.g., relapses or disability).

Risk of Getting COVID-19 in People With Multiple Sclerosis: A Case-Control Study.

BACKGROUND AND OBJECTIVES: Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR). METHODS: A case-control (1:2) study was set up. Cases included PwMS with a confirmed diagnosis of COVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score-matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administered DMT, previous DMT sequences, or the place where the last treatment was administered. RESULTS: A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02) with a higher risk of contracting COVID-19. Patients receiving natalizumab as last DMT (OR [95% CI]: 2.38 [1.66-3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16-2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34-2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home. DISCUSSION: This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective.

Mental Health in Multiple Sclerosis During the COVID-19 Outbreak: A Delicate Balance between Fear of Contagion and Resilience.

The current study aimed at exploring the relationship between objective disability, illness perceptions, resilience, fear of COVID-19, and psychological distress (i.e., anxiety, depression, and stress) in people with multiple sclerosis (pwMS) during the second wave of the COVID-19 outbreak. A group of 122 pwMS recruited in an Italian university hospital took part in this cross-sectional monocentric study. Hierarchical multiple linear regression analyses were performed to assess the strength of the hypothesized associations. Results indicated that, differently from cognitive impairment, motor disability was positively associated with anxiety. However, accounting for subjective illness perception, such association was no longer significant. Moreover, accounting for both protective and risk factors in the models, even illness perception was no longer significant, highlighting the central role of resilience and fear of COVID-19 in explaining the negative emotional outcomes. Implications for clinical interventions and psychoeducational trainings are discussed.

COVID-19 pandemic and mental distress in multiple sclerosis: Implications for clinical management.

BACKGROUND AND PURPOSE: In multiple sclerosis (MS), disease-related factors and dysfunctional coping might favor the development of mental distress induced by COVID-19 containment measures. Aim of this study was exploring the relationship between disability, coping strategies, daily life reorganization and neuropsychiatric symptoms in an Italian MS population during the COVID-19 lockdown, in order to identify potentially modifiable factors that could inform clinical management of mental distress in people with MS. METHODS: We explored the relationship between mental distress, disability and coping strategies in the Italian MS population under lockdown. Structural equation modeling was applied to information collected via web survey to identify modifiable factors that could account for mental distress. RESULTS: A total of 845 participants (497 with MS and 348 controls) were included in the study. The MS group had higher scores than the control group for depression (p = 0.005), but not for anxiety, emotional dyscontrol or sleep disturbances. The structural equation modeling explained 74% of the variance observed in depression score. Within the model, three latent factors were characterized from measured variables: motor disability and cognitive dysfunction contributed to disability (ß = 0.509 and ß = 0.836; p < 0.001); positive attitude and exercise contributed to active attitude (ß = 0.386 and ß = 0.297; p < 0.001); and avoidance, social support and watching television contributed to passive attitude (ß = 0.301, ß = 0.243 and ß = 0.212; p < 0.001). With regard to the relationship between latent factors and their influence on depression, disability contributed to passive attitude (ß = 0.855; p < 0.001), while both passive and active attitude significantly influenced depression (ß = 0.729 and ß = -0.456; p < 0.001). CONCLUSION: As a practical implication of our model, favoring exercise would enhance active attitude and its positive impact on mental well-being while, at the same time, reducing the negative impact of disability on depression, representing a valuable tool in facing COVID-19-related mental distress.

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.

Physical Exercise Moderates the Effects of Disability on Depression in People with Multiple Sclerosis during the COVID-19 Outbreak.

Physical disability impacts psychosocial wellbeing in people with multiple sclerosis. However, the role of physical activity in this context is still debated. By taking advantage of a previous survey, conducted online from 22 April to 7 May 2020, we performed a post-hoc analysis with the aim to assess the associations between disability, physical exercise, and mental health in multiple sclerosis. We retrieved the following data: (i) sociodemographic information, (ii) changes in lifestyle (including exercise), (iii) physical disability, as measured with the Patient-Determined Disease Steps scale, and (iv) anxiety feelings and depressive symptoms assessed via the items included in the Quality of Life in Neurological Disorders measurement system. Examination of the interaction plot showed that the effect of disability on depression, but not on anxious symptoms, was significant for all levels of physical exercise (low: b = 1.22, 95% C.I. 0.85, 1.58, p < 0.001; moderate: b = 0.95, 95% C.I. 0.66, 1.24, p < 0.001; and high: b = 0.68, 95% C.I. 0.24, 1.13, p = 0.003). Based on these data, we can conclude that disability significantly impacted depression during the COVID-19 pandemic, with physical activity playing a moderating role. Our results suggest that favoring exercise in multiple sclerosis (MS) would ameliorate psychological wellbeing regardless of the level of physical disability.

Prevalence of SARS-CoV-2 Antibodies in Multiple Sclerosis: The Hidden Part of the Iceberg.

BACKGROUND: We compared the prevalence of SARS-CoV-2 IgG/IgM in multiple sclerosis (MS), low-risk, and high-risk populations and explored possible clinical correlates. METHODS: In this cross-sectional study, we recruited MS patients, low-risk (university staff from non-clinical departments), and high-risk individuals (healthcare staff from COVID-19 wards) from 11 May to 15 June 2020. We used lateral flow immunoassay to detect SARS-CoV-2 IgG and IgM. We used t-test, Fisher's exact test, chi square test, or McNemar's test, as appropriate, to evaluate between-group differences. RESULTS: We recruited 310 MS patients (42.3 ± 12.4 years; females 67.1%), 862 low-risk individuals (42.9 ± 13.3 years; females 47.8%), and 235 high-risk individuals (39.4 ± 10.9 years; females 54.5%). The prevalence of SARS-CoV-2 IgG/IgM in MS patients (n = 9, 2.9%) was significantly lower than in the high-risk population (n = 25, 10.6%) (p < 0.001), and similar to the low-risk population (n = 11, 1.3%) (p = 0.057); these results were also confirmed after random matching by age and sex (1:1:1). No significant differences were found in demographic, clinical, treatment, and laboratory features. Among MS patients positive to SARS-CoV-2 IgG/IgM (n = 9), only two patients retrospectively reported mild and short-lasting COVID-19 symptoms. CONCLUSIONS: MS patients have similar risk of SARS-CoV-2 infection to the general population, and can be asymptomatic from COVID-19, also if using treatments with systemic immunosuppression.

Mild or no COVID-19 symptoms in cladribine-treated multiple sclerosis: Two cases and implications for clinical practice.

BACKGROUND: The use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) could affect COVID-19 outcomes by modulating the immune response, which, in turn, might favor viral replication and/or confer protection from COVID-19 induced inflammatory response CASE REPORT: We report on two MS patients treated with cladribine, with heterogeneous demographics and clinical features, who developed mild or no symptoms from COVID-19 and produced anti-SARS-CoV-2 antibodies, notwithstanding low lymphocyte levels. IMPLICATIONS: Benign COVID-19 clinical course and anti-SARS-CoV-2 antibody production can occur in MS patients with lymphopenia, suggesting the possibility to respond to COVID-19 vaccination, once available, in this vulnerable population.

Assessing disability and relapses in multiple sclerosis on tele-neurology.

BACKGROUND: As a consequence of the coronavirus disease 2019 (COVID-19) pandemic, a large amount of consultations will be delivered through tele-medicine, especially for diseases causing chronic disability and requiring immunomodulatory treatments, such as multiple sclerosis (MS). METHODS: We have hereby reviewed available tools for tele-neurology examination in MS, including components of neurological examination that can be assessed through video, patient-reported outcome measures (PROMs), and digital technology. RESULTS: Overall, we have suggested a battery for assessing MS disability and relapses on tele-medicine, which brings together conventional examination, PROMs (e.g., Patient Determined Disease Steps, MS Impact Scale), and cognitive tests (Symbol Digit Modalities Test) that can be delivered remotely and in multiple languages. DISCUSSION: The use of common tools for neurological examination could improve tele-neurology practice for both general neurologists and MS specialists, and quality of care for people with MS.

COVID-19 prevention and multiple sclerosis management: The SAFE pathway for the post-peak.

BACKGROUND: We hereby report on our experience from Naples (South Italy), where the peak of coronavirus disease 2019 (COVID-19) has already passed. METHODS: Assuming that COVID-19 will be circulating until vaccination and/or herd immunity is achieved (possibly not earlier than 2021), we have developed a protocol for the long-term management of multiple sclerosis (MS). RESULTS: We have defined a pathway for the access to the MS Centre with logistic, preventative and clinical recommendations, and have also included 14-day self-isolation and COVID-19 testing before some disease modifying treatments. DISCUSSION: Overall, we believe our experience could be helpful for MS management in the upcoming months.