Impact of vaccination on COVID-19 outcome in multiple sclerosis.

BACKGROUND: COVID-19 continues to challenge neurologists in counselling persons with multiple sclerosis (pwMS) regarding disease-modifying treatment (DMT) and vaccination. The objective here was to characterize predictors of COVID-19 outcome in pwMS. METHODS: We included pwMS with PCR-confirmed COVID-19 diagnosis from a nationwide population-based registry. COVID-19 outcome was classified as either mild or severe. Impact of DMT, specifically anti-CD20 monoclonal antibodies, and vaccination on COVID-19 outcome was determined by multivariable models adjusted for a-priori-risk (determined by a cumulative risk score comprising age, disability and comorbidities). RESULTS: Of 317 pwMS with COVID-19 (mean age 41.8 years [SD 12.4], 72.9% female, median EDSS 1.5 [range 0-8.5], 77% on DMT [16% on antiCD20]), 92.7% had a mild course and 7.3% a severe course with 2.2% dying from COVID-19. Ninety-seven pwMS (30.6%) were fully vaccinated. After a median 5 months from vaccination to SARS-CoV-2 infection (range 1-9), severe COVID-19 occurred in 2.1% of fully vaccinated pwMS compared to 9.5% in unvaccinated pwMS (p=0.018). A-priori-risk robustly predicted COVID-19 severity (R2 0.605; p<0.001). Adjusting for a-priori-risk, anti-CD20 treatment was associated with increased COVID-19 severity (odds ratio [OR] 3.3; R2 0.113; p=0.003), but exposure to any other DMT was not. Fully vaccinated pwMS showed a significantly decreased risk for severe COVID-19 (OR 0.21, R2 0.144, p<0.001). CONCLUSIONS: In a population-based MS cohort, COVID-19 course is primarily predicted by a-priori-risk (depending on age, disability and comorbidities) explaining about 60% of variance. Anti-CD20 treatment is associated with a moderately increased risk, while reassuringly vaccination provides protection from severe COVID-19.

Long-term outcome after COVID-19 infection in multiple sclerosis: a nation-wide multicenter matched-control study.

BACKGROUND: Long-term outcome after COVID-19 in patients with multiple sclerosis (pwMS) is scarcely studied and controlled data are lacking. OBJECTIVE: To compare long-term outcome after COVID-19 in pwMS to a matched control group of pwMS without COVID-19. METHODS: We included pwMS with PCR-confirmed diagnosis of COVID-19 and ≥6 months of follow-up available and, as a control group, pwMS matched 1:1 for age, sex, disability level and disease-modifying treatment type. RESULTS: Of 211 pwMS with COVID-19 (mean age 42.6 years [SD 12.2], 69% female, median EDSS 1.5 [range: 0-7.5], 16% antiCD20), 90.5% initially had a mild COVID-19 course. At follow-up, 70% had recovered completely 3 months (M3) after COVID-19, 83% after 6 months (M6) and 94% after 12 months (M12). Mild initial COVID-19 course was the only significant predictor of complete recovery (odds ratio [OR]: 10.5; p<0.001). Most frequent residual symptoms were fatigue (M3: 18.5%, M6: 13.7%, M12: 7.3%), hyposmia (M3: 13.7%, M6: 5.2%, M12: 1.7%) and dyspnea (M3: 7.1%, M6: 6.6%, M12: 2.8%). Compared to matched controls, fatigue, hyposmia and dyspnea were significantly more frequent at M3 and still slightly at M6, while there was no difference at M12. PwMS with COVID-19 had neither a significantly increased risk for relapses (OR 1.1; p=0.70) nor disability worsening (OR 0.96; p=0.60). DISCUSSION: Long-term outcome of COVID-19 is favourable in a large majority of pwMS with only a small proportion of patients suffering from persistent symptoms usually resolving after 3-6 months. COVID-19 is not associated with increased risk of relapse or disability.

Humoral immune response after COVID-19 in multiple sclerosis: A nation-wide Austrian study.

BACKGROUND: Knowledge on immunity after SARS-CoV-2 infection in patients with multiple sclerosis (pwMS) and the impact of disease-modifying treatment (DMT) is limited. OBJECTIVE: To evaluate degree, duration and potential predictors of specific humoral immune response in pwMS with prior COVID-19. METHODS: Anti-SARS-CoV-2 antibody testing was performed in pwMS with PCR-confirmed diagnosis of symptomatic COVID-19 from a nation-wide registry. Predictors of seropositivity were identified by multivariate regression models. RESULTS: In 125 pwMS (mean age = 42.4 years (SD = 12.3 years), 70% female), anti-SARS-CoV-2 antibodies were detected in 76.0% after a median of 5.2 months from positive PCR. Seropositivity rate was significantly lower in patients on IS-DMT (61.4%, p = 0.001) than without DMT or immunomodulatory DMT (80.6%; 86.0%, respectively). In multivariate analysis, IS-DMT was associated with reduced probability of seropositivity (odds ratio (OR): 0.51; 95% confidence interval (95% CI): 0.17-0.82; p < 0.001). Predefined subgroup analyses showed marked reduction of seropositivity in pwMS on rituximab/ocrelizumab (OR 0.15; 95% CI: 0.05-0.56; p < 0.001). Rate of seropositivity did not change significantly over 6 months. CONCLUSIONS: Humoral immunity is stable after SARS-CoV-2 infection in MS, but is reduced by immunosuppressive DMT, particularly anti-CD20 monoclonal antibodies. This provides important evidence for advising pwMS as well as for planning and prioritizing vaccination.

COVID-19 severity and mortality in multiple sclerosis are not associated with immunotherapy: Insights from a nation-wide Austrian registry.

BACKGROUND: The COVID-19 pandemic challenges neurologists in counselling patients with multiple sclerosis (pwMS) regarding their risk by SARS-CoV-2 and in guiding disease-modifying treatment (DMT). OBJECTIVE: To characterize the prevalence and outcome of COVID-19 in pwMS specifically associated with different DMT in a nationwide population-based study. METHODS: We included patients aged ≥18 years with a confirmed diagnosis of MS and a diagnosis of COVID-19 established between January 1, 2020 and December 31, 2020. We classified COVID-19 course as either mild, severe or fatal. Impact of DMT and specifically immunosuppressants (alemtuzumab, cladribine, fingolimod, ocrelizumab or rituximab) on COVID-19 outcome was determined by multivariable models, adjusted for a-priori-risk. RESULTS: Of 126 MS patients with COVID-19 (mean age 43.2 years [SD 13.4], 71% female), 86.5% had a mild course, 9.5% a severe course and 3.2% died from COVID-19. A-priori-risk significantly predicted COVID-19 severity (R2 0.814; p<0.001) and mortality (R2 0.664; p<0.001). Adjusting for this a-priori-risk, neither exposure to any DMT nor exposure to specific immunosuppressive DMT were significantly associated with COVID-19 severity (odds ratio [OR] 1.6; p = 0.667 and OR 1.9; p = 0.426) or mortality (OR 0.5; p = 0.711 and 2.1; 0.233) when compared to no DMT. CONCLUSIONS: In a population-based MS cohort, COVID-19 outcome was not associated with exposure to DMT and immunosuppressive DMT when accounting for other already known risk factors. This provides reassuring evidence that COVID-19 risk can be individually anticipated in MS and-except for a very small proportion of high-risk patients-treatment decisions should be primarily focused on treating MS rather than the pandemic.