Background

The Coronavirus Disease 2019 (COVID-19) pandemic has introduced uncertainties into the multiple sclerosis (MS) community and the focus so far has been the severity of infection among people with MS (pwMS) who have COVID-19. This approach has left questions about the risk of contracting disease in pwMS unanswered which has implications as society gradually returns to normal.

Objectives

To evaluate the trend of COVID-19 incidence in pwMS, their behaviour in response to the outbreak, and the effect of their demographic and clinical characteristics on the likelihood of contracting COVID-19.

Methods

The United Kingdom MS Register (UKMSR) has been collecting demographic and MS related data since 2011 from pwMS all over the UK. On 17 March 2020, existing participants of the UKMSR were asked to join the COVID-19 study. The study was also advertised through social media. In this on-going study, pwMS answer a COVID-19 related survey at participation and a different follow-up survey every two weeks depending on whether they report COVID-19.

Results

We estimate the nationwide overall incidence of COVID-19 in pwMS as 10% (n=522) among 5237 participants until 24 June 2020. The weekly incidence peaked during the 2^nd week after lockdown started on 23 March 2020 (13.2%) and remained high until it dropped to 3.5% in the 10^th week. The mean (standard deviation) age of the study population was 52.4 (11.9), 76.1% (n=3985) were female, and 95.7% (n=5012) were of white ethnicity. PwMS with a higher web-based Expanded Disability Status Scale (EDSS) score are more likely to self-isolate (odds ratio [OR] 1.389, 95%CI [confidence interval] 1.333−1.447). PwMS who are taking disease modifying therapies (DMTs) and those with progressive MS tend to self-isolate more (OR 1.259, 95%CI 1.059−1.497 and OR 1.245, 95% CI 1.013−1.531, respectively). Older age, progressive MS, and white ethnicity were associated with a lower likelihood of having COVID-19 (OR 0.969, 95%CI 0.957−0.982 and OR 0.595, 95% 0.422−0.838 and OR 0.495, 95%CI 0.347−0.705, respectively). Gender, EDSS, MS Impact Scale version 29 scores and DMTs did not alter the likelihood of contracting COVID-19.

Conclusions

To our knowledge, this is the largest community-based study of COVID-19 in pwMS worldwide. The trend of COVID-19 in pwMS is comparable to that of the UK general population. During a period with strict physical distancing measures, pwMS are not at an increased risk of contracting COVID-19.

Background

Despite the well-described association between vitamin D and MS, little is known about current behaviours surrounding vitamin D and the corresponding vitamin D status in this group at a population level across the UK. During the COVID-19 pandemic, interest in the role that vitamin D might play in reducing susceptibility to and severity of COVID-19 has come to the foreground.

Objectives

To determine the vitamin D status of the UK MS population, understand the factors that influence it, and examine how vitamin D supplementation affects the risk of COVID-19.

Methods

A cohort study using the UK MS Register was performed. Self-reported data surrounding vitamin D and remotely collected biological samples were collected. 1768 people with MS (pwMS) completed a questionnaire regarding vitamin D-influencing behaviours; dried blood spots were collected from 388 of these pwMS and 309 matched controls, and serum 25(OH)D was measured. Subsequently, 592 participants from this MS cohort prospectively completed questionnaires evaluating symptoms suggestive of COVID-19.

Results

Marked differences were observed between supplementation behaviours with pwMS more likely to take supplements (72% vs 26% controls, p<0.001), and at higher doses (median 1600 IU/day vs 600 IU/day in controls, p<0.001). Serum levels of 25(OH)D were higher in pwMS than controls (71nmol/L, IQR 48 vs 49nmol/L, IQR 27, p<0.001). People with MS who did not supplement had lower serum 25(OH)D levels than non-supplementing controls (median 38 nmol/L, IQR 35 vs 44 nmol/L, IQR 21, p<0.001). 71% of those self-diagnosed with COVID-19 reported taking vitamin D vs 72% without COVID-19. Median dose for those with COVID-19 was reported as 1000 IU/day vs 2000 IU/day in those without (p=0.682).

Conclusions

pwMS living in the UK are more likely to have adequate levels of vitamin D than controls, and is driven by the higher rate and dose of supplementation across this population. This has implications on the design and interpretation of any future clinical trials with vitamin D in this population. In addition, we found no evidence that vitamin D supplementation had an impact on susceptibility to COVID-19 in this population.

Background

Anxiety and depression are more common in people with multiple sclerosis (pwMS) compared to people without MS. The unpredictable nature of the COVID-19 pandemic has caused widespread distress, but it is unknown if it would affect pwMS disproportionately.

Objectives

To evaluate the impact of the COVID-19 pandemic on the mood and well-being of pwMS in the UK and compare it to that of controls.

Methods

The UK MS Register has been collecting Hospital Anxiety and Depression Scale (HADS) data of pwMS since 2011. In the mood and well-being UKMSR COVID-19 study, we asked pwMS (n=5240) and controls (n=376) to answer questions on General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) for depression and Revised Impact of Event Scale (IES-R) for post-traumatic stress disorder (PTSD) in addition to changes in their lifestyle and well-being during the COVID-19 outbreak.

Results

The HADS score of pwMS (n=2225) during the COVID-19 outbreak had not changed compared to the year before (mean difference 0.004, 95%CI -0.11−0.12, p=0.952 for anxiety and mean difference 0.05, 95%CI -0.05−0.15, p=0.283 for depression). The rate of anxiety (GAD-7>5) in male pwMS (37.2%) was more than controls (24.3%) (p=0.032) but was similar in female pwMS and controls. More male pwMS had moderate to severe depression (PHQ-9>9) compared to controls (28.5.4% vs 12.2%, p=0.003), but again, the rate was similar in females. More pwMS who had COVID-19, experienced anxiety or PTSD (IES-R>32) compared to those without the infection (54% vs 44%, p=0.018; 30.5% vs 22.5%, p=0.024, respectively). The rate of depression was similar in pwMS with or without symptoms of the disease. Anxiety, compared to the actual infection, was more strongly associated with subjective worsening of general health (57.1% vs 37.3%, with anxiety or COVID-19 respectively, p=0.008) or MS symptoms (61% vs 31.3%, p<0.001).

A high proportion of both pwMS and controls did not experience any change in the quality of their relationships. However, more pwMS reported worsening of their relationships compared to controls (21.4% vs 16.7%, p<0.001). The change in loneliness was similar between the two groups with 4 in 10 pwMS and controls feeling lonelier during the outbreak.

Conclusions

Anxiety during the COVID-19 pandemic is having a more profound effect on the general well-being of most patients compared to the infection itself.

Background

Multiple Sclerosis (MS) is a common neuro-inflammatory disorder caused by a combination of environmental exposures and genetic risk factors.

Objectives

To determine which environmental risk factors are associated with MS in UK Biobank, to validate an autosomal polygenic risk score for MS , and to determine whether genetic risk modifies the effect of environmental MS risk factors.

Methods

People with MS were identified within UK Biobank using ICD10-coded MS or self-report. Associations between environmental risk factors, HLA alleles, and MS risk were quantified using multivariable logistic regression. Interaction between environmental and genetic risk factors was quantified using the Attributable Proportion due to interaction (AP). Model fits were quantified using Nagelkerke’s pseudo-R² metric.

Results

Phenotype data were available for 2151 pwMS and 486,125 controls. Exposures associated with MS risk were childhood obesity (OR=1.39, 95%CI 1.22-1.58), smoking (OR=1.19, 95%CI 1.07-1.33), earlier menarche 0.95, 95%CI 0.92-0.98), HLA-DRB1*15 (OR_Homozygote 5.05, 95%CI 4.22-6.05) and lack of the HLA-A*02allele (OR_Homozygote=0.57, 95%CI 0.46-0.70). The autosomal polygenic risk score (PRS) was associated with MS disease status (OR_{Top-vs-bottom-decile}=3.96, 95%CI 3.11-5.04). There was evidence of positive (synergistic) interaction between elevated childhood body size and the PRS (AP 0.11, 95% CI 0.008 to 0.202, p = 0.036), and weaker evidence suggesting a possible interaction between smoking status prior to age 20 and the PRS (AP 0.098, 95% CI -0.013 to 0.194, p = 0.082).

Conclusions

This study provides novel evidence for an interaction between childhood obesity and a high burden of autosomal genetic risk. These findings have significant implications for our understanding of MS biology, and inform targeted planning of prevention strategies.

Background

Uveitis describes intraocular inflammation of the uveal tract. It may occur in the absence of a predisposing underlying condition, or may be secondary to a systemic autoimmune disease or ocular infection. An association with Multiple Sclerosis (MS) has also been observed.

Objectives

Our aim is to describe the demographics of patients with multiple sclerosis (MS) associated uveitis in a tertiary referral centre in London, UK, in order to add to the literature on the subject and inform discussions with patients with uveitis who may be concerned about developing MS. This is particularly important at present as anti-tumour necrosis factor alpha (anti-TNFα) therapies which are being used to treat refractory uveitis have also been linked to de novo demyelinating events and the exacerbation of demyelinating disease such as MS.

Methods

A retrospective audit was conducted using the online medical records system OpenEyes to identify all potential patients with a diagnosis of both uveitis and multiple sclerosis. Medical notes of all patients were reviewed by two independent researchers for suitability for inclusion. Patients were excluded for the following reasons: no online records, insufficient evidence in documentation to confirm MS or uveitis diagnosis, comorbid disease also linked to uveitis or follow up not under Moorfields. Patients who were included in the audit had had information recorded with respect to gender, ethnicity, type of MS, history of optic neuritis, site of uveitis, laterality of uveitis and age at diagnosis of uveitis and MS.

Results

16,309 patients were seen in the uveitis service between 2010 and 2017. Of these there were 106 patients with both uveitis and multiple sclerosis giving a prevalence of 0.65%. Of these 106 patients, 80 were female (75.5%) and 70 were white (66.0%). 41 of these patients had medical records which included the time at which they were diagnosed with uveitis and the mean length of follow up for these patients was 6.9 years. In this group, the most common type of uveitis associated with MS was intermediate (65.9%) and uveitis was most commonly bilateral (68.3%). MS was diagnosed at a younger average age than uveitis (35.3 vs 41.1 years old) and was diagnosed first in 61.0% of cases.

Conclusions

The 0.65% prevalence of multiple sclerosis in uveitis patients is broadly in keeping with previous estimates and is higher than the population prevalence of multiple sclerosis in the UK which ranges from 0.08 - 0.2%. This supports the association between these two conditions and suggests a common pathological process. Observations relating to the predominance of patients with both uveitis and MS being female, white and having intermediate uveitis may help inform discussions with patients regarding the risk of developing MS. The data from this audit could be used to inform a prospective study in which in-depth phenotypic and genotypic information is recorded for uveitis patients who are studied for the development of MS.