Potential Risks and Benefits of Multiple Sclerosis Immune Therapies in the COVID-19 Era: Clinical and Immunological Perspectives

Abstract

Coronavirus SARS-CoV2 has emerged as one of the greatest infectious disease health challenges in a century. Patients with multiple sclerosis (MS) have a particular vulnerability to infections through their use of immunosuppressive disease-modifying therapies (DMTs). Specific DMTs pose particular risk based on their mechanisms of action (MOA). As a result, patients require individualized approaches to starting new treatments and continuation of therapy. Additionally, vaccinations must be considered carefully, and individuals on long-term B cell-depleting therapies may have diminished immune responses to vaccination, based on preserved T cells and diminished but present antibody titers to influenza vaccines. We review the immunology behind these treatments and their impact on COVID-19, as well as the current recommendations for best practices for use of DMTs in patients with MS.

Keywords: COVID-19; Multiple sclerosis; SARS-CoV2; disease-modifying therapy; immunology; vaccination.

Fig. 1

The immune response to SARS-CoV-2 and potential sites of interaction with MS therapies. The virus binds to the angiotensin-converting enzyme-2 receptor (ACE-2R) on lung epithelial cells allowing cell entry, viral replication, and shedding. It interacts with lung dendritic cells through pattern recognition receptors (PRPs) and Toll-like receptors (TLRs) leading to the upregulation of proinflammatory cytokines, chemokines, and free radicals. An over-reactive immune response results in the “cytokine storm” that leads to the acute respiratory distress syndrome (ARDS), cardiomyopathy, and potentially encephalopathy. Both cellular (helper T cells, cytotoxic T cells, NK cells, and dendritic cells) and humoral (antibody-producing plasma cells and complement) immune responses are deployed to control the virus. MS therapies can potentially influence the immune response to the infection in beneficial or potentially harmful ways depending on whether the therapy is immunomodulatory (GA, IFNβ, DMF) or immunosuppressive (alemtuzumab, ocrelizumab, ofatumumab, and teriflunomide). Some may also have anti-viral effects (IFNβ and teriflunomide)