ABSTRACT
Introduction: People with multiple sclerosis (PwMS) treated with anti-CD20 therapies and fingolimod are less likely to successfully produce a humoral response to COVID-19 vaccines 1 and 2. Objective(s): To measure the humoral and/or cellular response to COVID-19 booster vaccinations in a cohort of PwMS who were previously seronegative after their initial COVID vaccine course. Aim(s): To determine whether there is a benefit of COVID-19 booster vaccinations for people with MS who are known to have had an attenuated response to initial vaccines. Method(s): We studied a cohort of PwMS all of whom were seronegative for anti-SARS-CoV-2 spike protein IgG after the 1st and 2nd COVID-19 vaccines, including PwMS treated with ocrelizumab (n=53), fingolimod (n=15), other DMTs (n=9) and no DMT (n=2). Dried blood spot +/- whole blood samples were obtained from participants at 2-8 weeks after their 3rd (n=79) and 4th (n=40) COVID-19 vaccines. Samples were used to measure anti-SARS-CoV-2 spike protein IgG (ELISA) and T-cell response (IFN-g release assay measured on whole blood). Result(s): Overall 27/79 (34%) who were seronegative after COVID vaccine 2 seroconverted after vaccine 3. Seroconversion rates were 17% for PwMS treated with ocrelizumab, 47% for fingolimod and 100% for other DMTs. A further 2/30 (7%) of those who remained seronegative after vaccine 3 seroconverted after vaccine 4. Anti-SARS-CoV-2 T-cell responses were measurable in 26/40 (65%) after vaccine 3 and 13/19 (68%) after vaccine 4 but were conspicuously absent in people treated with fingolimod. Overall, 75% of participants showed either humoral or cellular response after receiving 4 COVID vaccinations. PwMS with laboratory evidence of prior COVID-19 infection had higher measurable T-cell responses. Conclusion(s): Booster vaccinations for COVID-19 are associated with incremental benefits in measurable immunity in those with attenuated responses to the initial vaccine course. Overall, three quarters of those who were seronegative after COVID vaccines 1 & 2 had a measurable immune response after COVID vaccine 4. This data supports the use of booster vaccinations in pwMS at risk of attenuated vaccine response.
ABSTRACT
The COVID-19 study (clinicaltrials.gov:NCT04354519) is a prospective observational cohort launched on 17 March 2020 as part of the UKMSR. As of 24 April, out of 3910 participants, 237 (6.1% (95% CI 5.3% to 6.8%)) reported self-diagnosed COVID-19 among whom 54 (22.8% (17.5% to 28.2%)) also had a diagnosis by a healthcare professional based on symptoms and 37 (15.6% (11.2% to 20.6%)) a confirmed diagnosis by testing. Three participants reported hospitalisation due to COVID-19. No deaths were reported. Among 1283 siblings without MS, 79 (6.2%) had a reported diagnosis of COVID-19. Adjusting for age and gender, the likelihood of contracting COVID-19 in pwMS was similar to siblings (OR 1.180 (0.888 to 1.569)). Seven hundred and fifty-nine of 3812 participants reported that they were self-isolating and that they had been self-isolating for at least 2 weeks before symptom onset if they had COVID-19. Of these, 2 (0.3% (0% to 0.7%)) had self-diagnosed COVID-19 whereas 137 of 3053 participants not self-isolating (4.5% (3.8% to 5.2%)) had the disease. Participants on DMTs were less likely to have self-diagnosed COVID-19 (OR 0.640 (CI 0.428 to 0.957)), which remained significant after removing self-isolating participants (OR 0.633 (0.402 to 0.998)). High-efficacy DMTs reduced the likelihood of self-diagnosed COVID-19 compared with no DMTs (OR 0.540 (0.311 to 0.938)) but not compared with moderate-efficacy DMTs. Including webEDSS (n=2808) and physical MSIS-29v2 (n=3192) as additional predictors in the analysis showed no significant association with the likelihood of contracting COVID-19. The gender distribution was similar between participants with and without COVID-19. More participants with self-diagnosed COVID-19 reported themselves as having any ethnicity other than white compared with those without the disease (6.9% (3.9% to 10.1%) vs 3.8% (3.2% to 4.4%), p=0.019). Gender and ethnicity did not affect the likelihood of having COVID-19.
ABSTRACT
BACKGROUND: In March 2020, the United Kingdom Multiple Sclerosis Register (UKMSR) established an electronic case return form, designed collaboratively by MS neurologists, to record data about COVID-19 infections in people with MS (pwMS). OBJECTIVES: Examine how hospital admission and mortality are affected by disability, age and disease modifying treatments (DMTs) in people with Multiple Sclerosis with COVID-19. METHODS: Anonymised data were submitted by clinical teams. Regression models were tested for predictors of hospitalisation and mortality outcomes. Separate analyzes compared the first and second 'waves' of the pandemic. RESULTS: Univariable analysis found hospitalisation and mortality were associated with increasing age, male gender, comorbidities, severe disability, and progressive MS; severe disability showed the highest magnitude of association. Being on a DMT was associated with a small, lower risk. Multivariable analysis found only age and male gender were significant. Post hoc analysis demonstrated that factors were significant for hospitalisation but not mortality. In the second wave, hospitalisation and mortality were lower. Separate models of the first and second wave using age and gender found they had a more important role in the second wave. CONCLUSIONS: Features associated with poor outcome in COVID-19 are similar to other populations and being on a DMT was not found to be associated with adverse outcomes, consistent with smaller studies. Once in hospital, no factors were predictive of mortality. Reassuringly, mortality appears lower in the second wave.