ABSTRACT
Objective: Assess the SARS-CoV2 Spike antibody response in multiple sclerosis (MS) patients on high efficacy immunotherapies. Background: There is limited knowledge about SARS-CoV2 mRNA vaccine response in MS patients on immunotherapy. Design/Methods: Patients with MS, aged 18-65, on fingolimod, siponimod, ofatumumab, or ocrelizumab for at least 3 months prior to first mRNA SARS-CoV2 vaccine (Pfizer or Moderna) were offered enrollment. A cohort of healthy controls who received the mRNA vaccines were also enrolled. Blood samples for the SARS-CoV2 Spike antibody (Anti-SARS-CoV2 S, RocheElecsys) were collected 2-3 months after the second mRNA vaccine. The proportion who seroconverted (antibody>0.4 U/ml), and SARS-CoV2 Spike antibody levels were assessed. Results: A total of 39 MS patients (6 fingolimod, 33 ocrelizumab) and 31 controls were included in this interim analysis. 33%(13/39) of MS patients seroconverted, compared to 100%(31/31) in the control group, with an estimated risk difference of -0.67,(95% confidence interval: -0.81, -0.52;Fisher's exact test, p=9.0∗10-10 ). There was no difference in seroconversion rates between MS patients who received the Pfizer (34%, 10/29) versus the Moderna vaccine (30%, 3/10) (95% confidence interval -0.38, 0.29;Fisher's exact test=1). Seroconversion was found in 100% (31/31) of controls, 66.7% (4/6) of fingolimod-treated patients, and 27.3% (9/33) of ocrelizumab-treated patients (three group comparison, Fisher's exact test p-value =2.7∗10 -10). The median Spike antibody level was <0.4 U/ml in MS patients, and 1,663 U/ml in controls (Wilcoxon rank sum test, p-value= 1.0∗10-12 ). The median Spike antibody level in the ocrelizumab group was <0.4 U/ml, 3.45 U/ml in the fingolimod group, and 1,663 U/ml in the control group (Kruskal Wallis test, p-value=5.9∗10-12 ). Total IgG correlated with Spike antibody levels in the ocrelizumab-treated group only (Spearman correlation, p=0.025). Conclusions: MS patients on ocrelizumab and fingolimod have significantly lower rates of seroconversion, and lower median Spike antibody levels in response to the mRNA SARS-CoV2 vaccines compared to controls.
ABSTRACT
Introduction: SARs-CoV-19 infection (COVID-19) is associated with various neurologic symptoms. A full range of neurologic outcomes in patients with multiple sclerosis (MS) and related disorders (MSRD) following COVID-19 illness is not well understood. Objectives: To investigate neurologic outcomes in patients with MSRD post COVID-19. Methods: This was a retrospective medical records review study of adult patients with MSRD who had confirmed COVID-19 infection at the Brigham MS Center, between March 9, 2020 and April 1, 2021. We reviewed demographics, MS history, COVID-19 outcomes, neurologic symptoms, and MRI data. Neurologic worsening post-COVID-19 was defined as having a relapse, pseudo-relapse, new brain MRI activity, worsening of preexisting MS symptoms, or development of other long-term neurologic symptoms. Results: 111 patients, 85 (77%) females, with a mean [SD] age of 49 [12.2] years, and a mean [SD] EDSS of 3.4 [2.7] were identified. 72 (65%) had relapsing remitting MS, 21 (19%) had secondary and 8 (7%) had primary progressive MS, 2 (2%) had clinically isolated syndrome, and 8 (7%) had related disorders. 17 (15%) patients were asymptomatic, 63 (57%) had mild COVID-19 defined as symptoms not requiring hospitalization, 22 (20%) had moderate COVID-19 requiring hospitalization, 3 (3%) had severe COVID-19 requiring ICU admission, 2 (2%) died due to COVID-19 and 4 (4%) had unknown COVID-19 outcomes. 85 (77%) completely recovered from COVID-19. 41 patients (37%) had neurologic worsening post COVID-19. Of those with neurologic worsening, 19 (46%) had pseudo-relapses, 2 (4.8%) had relapses, and 27 (66%) patients reported worsening of preexisting MS symptoms, or other new longterm neurologic symptoms at the last follow up visit. 55 patients had brain MRI scans post COVID-19 with a mean [SD] between MRI and infection of 144.6 [107.8] days. 5 patients had new lesions on T2 or T1Gd+ scans. Neurologic worsening was associated with moderate or severe COVID-19 (p=0.0006), treatment for COVID-19 (p=0.0061), and incomplete COVID-19 recovery (p=0.0267) but not with age, sex, MS type, ethnicity, disease duration, EDSS, vitamin D use, or type or presence of disease modifying therapy. Conclusions: COVID-19 severity and lack of complete systemic recovery was associated with new or worsening neurologic symptoms in 37% of MSRD patients.