Multiple sclerosis in the era of COVID-19: disease course, DMTs and SARS-CoV2 vaccinations

Abstract

Purpose of reviewAs of January 21st 2022, over 340 million are confirmed cases of coronavirus disease 2019 (COVID-19), including nearly 5.6 million deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is neurotropic and affects the neural parenchyma through direct viral invasion from the nasal mucosa and postinfectious cytokine storm. Further challenges of SARS-CoV-2 infection are nowadays linked to variants of concern. Multiple sclerosis is an inflammatory and progressive degenerative disorder of the central nervous system commonly affecting young adults and potentially generating irreversible disability. Since the beginning of the SARS-CoV-2 pandemic, people with multiple sclerosis (pwMS) have been considered 'extra' vulnerable because of the immune-mediated nature of the disease, the disability status, and the immunomodulatory therapies potentially increasing the risk for viral infection. Today multiple sclerosis neurologists are faced with several challenges in the management of pwMS to both prevent SARS-CoV-2 infection and protection from disease worsening. We aimed to highlight today's most relevant facts about the complex management of pwMS in the COVID-19 era. Recent findingsThe incidence of COVID-19 among pwMS does not differ from the general population. The prognosis of COVID-19 among pwMS is driven by older age, male sex, nonambulatory status, comorbidity as in the general population, as well as by corticosteroid treatment and B-cell depleting agents which decrease seropositivity from SARS-CoV-2 infection and immune responses to SARS-CoV-2 vaccination. Summary Disease modifying treatments (DMTs) should be regularly continued in relation to SARS-CoV-2 vaccination, but an ad hoc timing is required with B-cell depleting agents. SARS-CoV-2 vaccination is recommended in pwMS with willingness improving through health education programs. Multiple sclerosis does not seem to worsen after SARS-Cov2 vaccination but COVID-19 may enhance disease activity.

Clinical effectiveness of coronavirus disease 2019 vaccination in patients with multiple sclerosis stratified by disease‐modifying treatment

“…No difference in clinical effectiveness between mRNAbased and viral vector vaccines was found, nor between any of the different vaccines individually, but our study was not sufficiently powered to assess this explorative endpoint. Vaccination coverage (i.e., at least fully vaccinated) was 76.6% and corresponds well with the vaccine willingness in patients with MS described in the literature [33]. Younger age, low education levels, lower perceived risk for COVID-19 infection and higher functional disability states are amongst the factors that have been independently associated with reduced vaccine acceptance [6].…”

Occurrence and Severity of Coronavirus Disease 2019 Are Associated With Clinical Disability Worsening in Patients With Multiple Sclerosis

“…The exact way in which SARS-CoV-2 affects the CNS seems to rely for a large part on secondary immunologic consequences (e.g., blood-brain barrier breakdown, tissue inflammation, hypoxia, and coagulopathy) rather than direct viral invasion. 21 - 23 Second, based on (1) observations in other upper respiratory infections, (2) the accumulating number of acute demyelinating CNS episodes associated with COVID-19, and (3) descriptions of potential inflammatory crossroads between MS and SARS-CoV-2 infection, it has been speculated that COVID-19 may increase the risk of relapses in patients with MS. 24 - 26 However, clinical studies have provided conflicting results and, overall, have not been able to confirm this association. 20 , 27 - 29 With regard to our cohort, post–COVID-19 relapse activity was comparable with the existing literature but could not be identified as the driving force behind the observed EDSS worsening.…”

“… 41 Hesitancy and/or unwillingness to receive vaccination against SARS-CoV-2 ranges between 15% and 30% in patients with MS and is often instilled by safety concerns, despite the fact that the current literature does not show an increased risk for reactogenicity, serious adverse events, or relapse activity. 24 , 25 Our cohort presented with a lower coverage rate, but data collection started well before the rollout of the vaccination campaign in Belgium. At present, COVID-19 vaccination is strongly advised for most people with MS, as it is the general view that potential benefits outweigh any possible risks in the vast majority of cases.…”

COVID-19 Vaccination Coverage and Associated Factors in Patients with Multiple Sclerosis

“…Since the onset of the COVID-19 pandemic caused by the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), persons with MS have been considered “extra” vulnerable due to the immune-mediated nature of their disease, disability status, and immunomodulating treatments [ 9 ]. Indeed, to date, SARS-CoV-2 infection-related mortality rates of up to 4% have been reported in these individuals [ 10 , 11 ]; furthermore, higher rates of infection and hospitalization due to COVID-19 have been reported in MS patients than in the general population [ 12 ].…”