ABSTRACT
Background: People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods: Data from 12 data-sources in 28 countries were aggregated. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression. Results: 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29-2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36; aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Conclusions: Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission, suggesting their use may be a risk factor for more severe COVID-19.
ABSTRACT
Despite its limitations, the Kurtzke Expanded Disability Status Scale (EDSS) is the gold standard in assessing physical disability in multiple sclerosis (MS). Sustained progression in EDSS has been used widely as the endpoint in therapeutic studies. However, the patients’ disability often fluctuates or improves over time; and up to half of the patients with “sustained progression” of EDSS eventually regress to their baseline. It is, therefore, not a sensitive measure to define irreversible progression of disease. The Multiple Sclerosis Severity Score (MSSS) is a useful measure of MS severity, incorporating the EDSS and disease duration. It has some prognostic significance for individuals with mild or severe disease, but is best suited to cross-sectional comparative studies. Cognitive impairment in MS is often considerable, and principally affects the domains of attention, vigilance, processing speed, working memory and executive function. Tests such as paced auditory serial addition test (PASAT) and the symbol digit substitution test (SDT) are therefore quite sensitive to change over time. The Multiple Sclerosis Functional Composite (MSFC), a score combining a measure of lower limb function (timed walk), upper limb function (nine-hole peg test) and cognitive function (PASAT), is useful to detect disability progression in MS trials, as it is sensitive to change over time, but is too time-consuming to become adopted in clinical practice.
