ABSTRACT
Background: As the COVID-19 pandemic continues, evidencebased clinical guidance for managing the care of people with multiple sclerosis (MS) is an ongoing concern. In recent months, data from cohorts of people with MS has indicated that certain demographic and clinical characteristics, including use of some disease- modifying therapies (DMTs), leads to worse outcomes from SARS-CoV-2 infection. The COVID-19 in MS global data sharing initiative, which now includes over 4,500 confirmed COVID- 19 cases in people with MS, gives the opportunity to corroborate previous findings with greater certainty. Methods: Clinician-reported data from 32 countries were aggregated into a dataset of 5,543 patients who had suspected or confirmed COVID-19. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes. These outcomes (hospitalisation, admission to ICU, requiring artificial ventilation, and death) were assessed in patients with suspected/ confirmed COVID-19 using multilevel mixed-effects logistic regression. All models were corrected for age, sex, EDSS, and MS type. DMTs were individually compared to glatiramer acetate (GA), as well as to pooled other DMTs and natalizumab. Results: Of 5,543 patients in the clinician-reported dataset, 909 with suspected and 4,634 with confirmed COVID-19 were included in the analysis. Previous demographic findings were confirmed: male sex, older age, progressive MS, and higher disability were associated with worse outcomes from SARS-CoV-2 infection. Use of anti-CD20 DMTs (ocrelizumab and rituximab) was associated with worse COVID-19 outcomes. Compared to GA, ocrelizumab and rituximab were associated with increased risk of hospitalisation (aOR=1.61(95%CI=1.06-2.43);aOR=2.42(95%CI=1.54-3.81) and ICU admission (aOR=3.13(95%CI=1.22-8.00);aOR=4.46 (95%CI=1.64-12.09)). Rituximab was associated with increased risk of artificial ventilation (aOR=3.57(95%CI=1.38-9.20));ocrelizumab showed a positive trend (aOR=1.86(95%CI=0.76-4.55). Rituximab showed a positive trend with increased risk of death (aOR=2.74(95%CI=0.68-11.09). Associations persisted on restriction to confirmed COVID-19 cases. Conclusions: Analysing the largest international real world dataset of people with MS who have suspected or confirmed COVID- 19 confirms previous findings that male sex, older age, progressive MS, higher disability, the use of anti-CD20 medication (ocrelizumab and rituximab) are associated with worse COVID-19 outcomes.
ABSTRACT
Introduction: Limited data on SARS-CoV-2 vaccine reactogenicity in persons with multiple sclerosis (PwMS) exists and it is of interest due to the novel vaccine strategies deployed and the uncertain impact of disease modifying therapies (DMTs). Objective: To report real-world data on SARS-CoV-2 vaccine reactions in PwMS in the context of DMTs. Aim: To identify sociodemographic and clinical attributes associated with SARS-CoV-2 vaccine reactogenicity in PwMS. Methods: PwMS participating in iConquerMS (an online research network) completed detailed online surveys between 3/2021- 6/2021, and reported their SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, or other) reactions within 24 hours (reported as none, mild, moderate, or severe), and other attributes, including DMT use. Multivariable models characterized associations between predictors and reactogenicity after the 1st and 2nd vaccination. Results: In 719 PwMS, 64% reported a reaction and 17% reported a severe reaction after the 1st vaccine, which were primarily experiences of pain at injection site, fatigue, headache, and malaise. Younger age, being female, a prior SARS-CoV-2 infection, and receiving the ChAdOx1 nCoV-19 versus the BNT162b2 vaccine were independently associated with experiencing a reaction. Similar relationships were observed for experiencing a severe reaction, including higher reactogenicity for PwMS with greater physical impairment and lower reactogenicity for PwMS treated with an alpha4-integrin blocker or sphingosine-1-phosphate receptor modulator (SIPR). In 441 PwMS who received two vaccinations, 74% reported a reaction and 22% reported a severe reaction after the 2nd vaccine. Younger PwMS and those who received the mRNA-1273 versus the BNT162b2 vaccine reported higher reactogenicity, while those on a S1PR or fumarate reported fewer reactions. Similar relationships for age, vaccine type, and S1PR treatment were observed for experiencing a severe reaction after the 2nd vaccine. There were no differences in reactogenicity by MS subtype, disease duration, or for B-cell depleting DMTs across models. Conclusions: Factors associated with SARS-CoV-2 vaccine reactogenicity in the general population were similarly associated in PwMS. Intriguingly, PwMS on specific DMTs were significantly less likely to report vaccine reactions.