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

Abstract

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.

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

“…The Austrian MS-COVID-19 registry (AUT-MuSC), a collaboration of MS centres certified by the Austrian Neurological Society (ÖGN) adhering to a common and controlled quality standard of excellence, documents epidemiological, clinical and paraclinical data of pwMS suffering a SARS-CoV-2 infection, as described in detail elsewhere. 9 …”

Severe outcomes of COVID-19 among patients with multiple sclerosis under anti-CD-20 therapies: A systematic review and meta-analysis

“…Consistently, in a North American study, both ocrelizumab and rituximab were associated with hospitalization, but association was stronger for rituximab (Salter et al, 2021). However, the role of anti-CD20 treatments in the COVID-19 severity were not always confirmed (Bsteh et al, 2021;Louapre et al, 2020). Therefore, it is relevant to undertake a comprehensive systematic review for estimating the mortality rate among patients under these therapies, for exploring all their available characteristics and in general for estimating their rates of severe COVID-19 events.…”

“…All selected articles were rigorously appraised by two authors according to a modified version of the Dutch Cochrane center critical review checklist proposed by MOOSE (Stroup et al, 2000). Key domains assessed by the MOOSE tool include: (I) Clear definition of study population; (II) Clear definition of outcomes and outcomes assessment; (III) Independent assessment of outcome parameters; (IV) Sufficient The presence of SARS-CoV2 antibodies in MS patients (Armstrong et al, 2021;Arrambide et al, 2021;Barzegar et al, 2020Barzegar et al, , 2021Bose and Galetta, 2021;Bsteh et al, 2021;Chaudhry et al, 2020;Ciampi et al, 2020;Conte, 2020;Czarnowska et al, 2021;D'Abramo et al, 2021;Devogelaere et al, 2020;Fernandez-Diaz et al, 2021;Fragoso et al, 2021;Garg et al, 2020;Hervas-Garcia, 2020;Loonstra et al, 2020;Louapre et al, 2020;Montero-Escribano et al, 2020;Olivares Gazca et al, 2020;Sahraian et al, 2020;Salter et al, 2021;Sen et al, 2021;Sormani et al, 2021b,a;Spelman et al, 2021;Stroup et al, 2000;Suwanwongse and Shabarek, 2020;Thornton and Harel, 2020 *Data provided by the authors but not published.…”

Development of humoral and cellular immunological memory against SARS-CoV-2 despite B cell depleting treatment in multiple sclerosis

“…However, caution should be exerted when interpreting these types of data since they rely on spontaneous reporting with difficulties in completely controlling for confounders. In addition, in persons with MS (pwMS), established risk factors seem to outweigh the impact of disease-modulatory therapies (DMTs) on COVID-19 outcomes (Bsteh et al, 2021;Louapre et al, 2020;Zabalza et al, 2020). Nevertheless, a recent pre-pandemic study showed an increased rate of severe infections with B cell depletion compared to other DMTs in pwMS (Luna et al, 2020).…”