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COVID-19 and MS: lessons learned thus far

Presented by
Prof. Céline Louapre, Sorbonne University, France

In the era of COVID-19, the decision-making process when choosing a treatment for relapsing-remitting MS has not changed a great deal, given the major benefits of high-efficacy therapies. Both higher neurological disability and anti-CD20 therapy have been associated with more severe COVID-19. Vaccination protects against severe COVID-19, except in patients who use anti-CD20 therapies.

An overview of the insights that have been gathered over the past 2 years on COVID-19 in patients with MS [1,2] was provided by Prof. Céline Louapre (Sorbonne University, France) [3]. At the start of the pandemic, there were some key questions to be answered for MS patients:

  • How severe is COVID-19 in patients with MS?
  • What are the risk factors for developing a severe form of COVID-19 in patients with MS?
  • Does COVID-19 modify the course of MS?
  • Could COVID-19 change MS incidence?
  • Does vaccination effectively prevent COVID-19 in MS patients?

An observational study in 347 MS patients who got COVID-19 between March and May 2020, found that 73 (21%) were hospitalised and 12 (3.5%) had died [4]. Age, Expanded Disability Status Scale (EDSS), and obesity were independent risk factors for severe COVID-19. Most patients who died were in the group which did not receive any MS treatment. Neurological disability strongly predicted severe COVID-19: an EDSS of 6 or more was associated with an odds ratio (OR) of severe outcome of 6.33. A pooled analysis of 1,787 symptomatic COVID-19 patients with MS showed that around 12% were hospitalised and 2.7% were admitted to the ICU or died [5]. Anti-CD20 medication (OR 2.05) and methylprednisolone (OR 2.71) were associated with severe outcome of COVID-19 (P<0.001).

To further specify these outcomes and put them into a better perspective, Prof. Louapre went on to present very recent, unpublished results of 2,709 patients in the COVISEP registry (NCT04355611). Data cut-off was in July 2022, at which point the group had a mean age of 44 years, a mean EDSS of 2.0, and included 390 secondary progressive MS patients and 208 primary progressive MS patients. In total, 251 patients (9.3%) were hospitalised and 45 (1.7%) were admitted to the ICU or died. Hospitalisation rate was around 15% until the fifth wave of COVID-19, mainly caused by the Omicron variant, after which hospitalisation percentage dropped. Before the Omicron wave, COVID-19 severity was associated with EDSS and with anti-CD20 medication, which was still the case during the Omicron wave, despite the lower number of patients (see Figure). Among vaccinated MS patients (>2 injections) only anti-CD20 medication was associated with COVID-19 severity, with an OR of 8.2 (95% CI 2.8–24.1) for severe COVID-19.

Figure: COVID-19 severity associated with EDSS and anti-CD20 medication [3]

EDSS, Expanded Disability Status Scale.

To investigate whether EDSS and anti-CD20 medication are cumulative risk factors for severe COVID-19, Prof. Louapre and colleagues set up a post-hoc study including 1,005 relapsing-remitting MS patients on high-efficacy DMTs: 424 on anti-CD20 therapy and 581, with very similar characteristics, on another high-efficacy therapy (natalizumab or fingolimod). The rate of severe COVID-19 in both groups was significantly different: 13.1% and 2.6%, respectively. Applying a logistic regression model weighted by propensity scores still revealed a higher risk of severe COVID-19 in the anti-CD20 group (OR 5.02; 95% CI 2.71–9.30; P<0.001), present in all subgroups. However, this deleterious effect of anti-CD20 therapy was absent in patients with progressive MS, with an adjusted OR of 1.21 (95% CI 0.70–2.70).

So, in patients with progressive MS, the risk-benefit ratio was different: an increased risk of severe COVID-19 in patients with higher disability must be weighed against the modest efficacy of anti-CD20 therapy or in fact any treatment at this stage of the disease.

  1. Pugliatti M, et al. Curr Opin Neurol. 2022;35(3):319–327.
  2. Pugliatti M, et al. Front Immunol. 2022;13:1045101.
  3. Louapre C. Looking back, what have we learnt? Abstract O136, ECTRIMS 2022, 26–28 October, Amsterdam, the Netherlands.
  4. Louapre C, et al. JAMA Neurol. 2020;77(9):1079–88.
  5. Sormani MP, et al. Ann Clin Transl Neurol. 2021;8(8):1738–44.

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