PURPOSE OF REVIEW: As 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 FINDINGS: The 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.

Brain and Mind Center University of Sydney Sydney Australia

Center for Neuroinflammation and Experimental Therapeutics University of Pennsylvania Perelman School of Medicine

Department of Medicine Faculty of Medicine Universidad Complutense de Madrid

Department of Neurology Hospital Clínico San Carlos IDISSC Madrid Spain

Department of Neurology Medical University of Vienna Vienna Austria

Department of Neurology Palacky University Olomouc Olomouc Czech Republic

Department of Neurology Universitätsklinikum Düsseldorf Medical Faculty Heinrich Heine University Düsseldorf Germany

Department of Neurology University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

Department of Neuroscience and Rehabilitation S Anna University Hospital Ferrara

Department of Neuroscience and Rehabilitation University of Ferrara

Interdepartmental Research Center on Multiple Sclerosis and other neuroinflammatory and degenerative diseases University of Ferrara Italy

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COVID-19 and multiple sclerosis: challenges and lessons for patient care