Disease Modifying Therapies and COVID-19 Severity in Multiple Sclerosis

Abstract

15,16 and the Musc-19 Study GroupObjective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists.

Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2

“…Their use is associated with IgM deficiency in a substantial number of patients, while their impact on IgG and IgA levels is more limited (Kridin and Ahmed, 2020). In line with our data, recent studies reported that anti-CD20 therapy could be associated with a higher susceptibility to contract SARS-CoV-2 and develop severe COVID-19 (Guilpain et al, 2020;Hughes et al, 2020;Safavi et al, 2020;Schulze-Koops et al, 2020;Sharmeen et al, 2020;Sormani et al, 2020). Whether this is associated to the preferential depletion of IgM-producing B cells by these treatments (Looney et al, 2008) remains to be shown.…”

COVID-19 in patients with multiple sclerosis undergoing disease-modifying treatments

“…In one case, fatal outcome was likely due to multiple associated comorbidities (Table 1 and S-Table 2). 34,36 Alemtuzumab and Cladribine Alemtuzumab is a monoclonal antibody targeting the CD52 antigen, approved for the treatment of RRMS, administered in two therapeutic cycles, 12 months apart. Administration of alemtuzumab leads to a longterm decrease in T cells and short-term decrease in B cells, followed by repopulation.…”

The Impact of Immunosuppression and Autoimmune Disease on Severe Outcomes in Patients Hospitalized with COVID-19

“…In a series of 82 patients with confirmed or highly suspected COVID-19, all of whom had an AD, patients who did not require hospital treatment for COVID-19 were more likely to be on immunosuppressive therapy than those who were hospitalized (76% vs 50%) [19]. In an Italian study, 123 of 784 (15.7%) patients with MS and suspected or confirmed COVID-19, 83% whom were receiving disease-modifying therapy (DMT) for MS, had a severe course of infection [20]; this was a similar percentage to that reported in the general population [21]. In univariate analysis, the odds of severe COVID-19 were significantly higher in patients not receiving DMT (OR 2.83; p < 0.001), but varied according to the specific drug used in DMT-treated patients.…”