Objective The purpose of this study was to investigate the effect of disease modifying therapies on immune response to severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccines in people with multiple sclerosis (MS). Methods Four hundred seventy‐three people with MS provided one or more dried blood spot samples. Information about coronavirus disease 2019 (COVID‐19) and vaccine history, medical, and drug history were extracted from questionnaires and medical records. Dried blood spots were eluted and tested for antibodies to SARS‐CoV‐2. Antibody titers were partitioned into tertiles with people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following the SARS‐CoV‐2 vaccine according to disease modifying therapy. We used regression modeling to explore the effect of vaccine timing, treatment duration, age, vaccine type, and lymphocyte count on vaccine response. Results Compared to no disease modifying therapy, the use of anti‐CD20 monoclonal antibodies (odds ratio = 0.03, 95% confidence interval [CI] = 0.01–0.06, p < 0.001) and fingolimod (odds ratio = 0.04; 95% CI = 0.01–0.12) were associated with lower seroconversion following the SARS‐CoV‐2 vaccine. All other drugs did not differ significantly from the untreated cohort. Both time since last anti‐CD20 treatment and total time on treatment were significantly associated with the response to the vaccination. The vaccine type significantly predicted seroconversion, but not in those on anti‐CD20 medications. Preliminary data on cellular T‐cell immunity showed 40% of seronegative subjects had measurable anti‐SARS‐CoV‐2 T cell responses. Interpretation Some disease modifying therapies convey risk of attenuated serological response to SARS‐CoV‐2 vaccination in people with MS. We provide recommendations for the practical management of this patient group. ANN NEUROL 2021

Objective: To investigate the effect of disease modifying therapies on serological response to SARS-CoV2 vaccines in people with multiple sclerosis Methods: 473 people with multiple sclerosis from 5 centres provided one or more dried blood spot samples and a questionnaire about COVID-19 and vaccine history. Information about disease and drug history was extracted from their medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV2 receptor binding domain. Seropositivity was expressed according to validated cut-off indices. Antibody titers were partitioned into tertiles using data from people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (Univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following SARS-CoV2 vaccine according to disease modifying therapy. We used regression modelling to explore the effect of factors including vaccine timing, treatment duration, age, vaccine type and lymphocyte count on vaccine response. Results: Compared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio 0.03; 95% confidence interval 0.01-0.06, p<0.001) and fingolimod (odds ratio 0.41; 95% confidence interval 0.01-0.12) were associated with lower seroconversion following SARS-CoV2 vaccine. All other drug groups did not differ significantly from the untreated cohort. Both time since last anti-CD20 treatment and total time on treatment were significantly related with serological response to vaccination. Vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications. Interpretation: Some disease modifying therapies carry a risk of attenuated response to SARS-CoV2 vaccination in people with MS. We provide recommendations for the practical management of this patient group.

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Background: Iron rims (IRs) surrounding white matter lesions (WMLs) are suggested to predict a more severe disease course. Only small longitudinal cohorts of patients with and without iron rim lesions (IRLs) have been reported so far. Objective: To assess whether the presence and number of IRLs in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS) are associated with long-term disability or progressive disease. Methods: Ninety-one CIS/MS patients were recruited between 2008 and 2013 and scanned with 7 T magnetic resonance imaging (MRI). Expanded Disability Status Scale (EDSS) was used to calculate Age-related Multiple Sclerosis Severity Score (ARMSS) at the time of scan and at the latest clinical follow-up after 9 years. WMLs were assessed for the presence of IRL using Susceptibility weighted imaging (SWI)-filtered phase images. Results: In all, 132 IRLs were detected in 42 patients (46%); 9% of WMLs had IRs; 54% of the cohort had no rims, 30% had 1–3 rims and 16% had ⩾4. Patients with IRL had a higher EDSS and ARMSS. Presence of IRL was also a predictor of long-term disability, especially in patients with ⩾4 IRLs. IRLs have a greater impact on disability compared to the WML number and volume. Conclusion: The presence and number of perilesional IR on MRI hold prognostic value for long-term clinical disability in MS.

Importance: Uncertainties remain about the benefit of a 3rd COVID-19 vaccine for people with attenuated response to earlier vaccines. This is of particular relevance for people with multiple sclerosis (pwMS) treated with anti-CD20 therapies and fingolimod, who have substantially reduced antibody responses to initial vaccine course. Objective: To report humoral and T-cell responses following COVID-19 vaccine 3 in pwMS who were seronegative after COVID-19 vaccines 1&2. Design, setting and participants: PwMS taking part in a seroprevalence study without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Data on demographics, MS treatment, and COVID-19 infection/vaccine dates were derived from the medical notes. Methods: Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. The relationship between evidence of prior COVID-19 infection and immune response to COVID-19 vaccine 3 was evaluated using Fishers exact test. Results: Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There no association between laboratory evidence of prior COVID-19 infection and anti-spike seroconversion following COVID-19 vaccine 3. Conclusions: Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.

IntroductionIdentifying accurate prognostic imaging biomarkers in multiple sclerosis (MS) is crucial. Iron rims (IR) surrounding white matter lesions (WML) are suggested to predict a more severe disease course. Only small longitudinal cohorts of patients with and without IRL have been reported so far.ObjectiveTo assess if the presence and number of IRL in patients with CIS and MS are associated with worse long-term clinical disability.MethodsNinety-one CIS/MS patients were recruited between 2008 and 2013 and scanned with 7T MRI. Age-Related Multiple Sclerosis Score (ARMSS), a validated measure of disease severity, was calculated for patients at the time of scan and at the latest clinical follow-up after 9 years. WMLs were assessed for the presence of IRL using SWI-filtered phase images.Results132 IRLs were detected in 42 patients (46%). 9% of WMLs had IR. 54% of the cohort had no rims, 30% had 1-3 rims and 16% had ≥4. Patients with IRL at baseline had a higher EDSS and ARMSS. Presence of IRL was also a predictor of long-term disability especially in those patients with ≥4 IRL. The effect of IRL on disability was greater than the baseline WML numbers, another known prognostic biomarker.ConclusionThe presence and number of perilesional IR at a baseline scan hold prognostic value for long term clinical disability in MS.

OBJECTIVE To determine whether brief attendance for outpatient radiological investigations is associated with increased risk of clinically significant coronavirus disease 2019 (covid19) infection. DESIGN Observational cohort study with a historical control. SETTING 2 large UK University Hospitals located in Nottingham and Cardiff. PARTICIPANTS All 47,340 patients who attended an outpatient radiology appointment at Nottingham University Hospitals and University Hospital of Wales during the first wave of the pandemic in 2020, and 70,655 patients that comprised the control cohort who attended for outpatient radiology the same period in 2019. MAIN OUTCOME MEASURES The risk of developing clinically significant covid-19 infection within 28 days of attending a radiological examination. Covid19 infection rates for the 2020 cohort were compared against a control group who attended in 2019. RESULTS 84 positive SARSCoV2 tests were temporally associated with 47,340 radiological examinations across two hospitals in 2020. This low infection rate was higher than the 2019 control cohort; OR 2.507 (1.766 3.559) and equates to an approximate 1 positive covid19 infection per 1000 radiology investigations. CONCLUSIONS Our data suggests that attending hospitals for outpatient radiological investigations during the pandemic is associated with a very small absolute risk of acquiring clinically significant covid19 infection. It is unlikely that this risk is directly attributable to radiology attendance, considering the reasons leading individuals to attend hospitals during the pandemic, the true attributable risk will likely be even lower. TRIAL REGISTRATION ClinicalTrials.gov NCT04544176