Systematic review of risk of SARS-CoV-2 infection and severity of COVID-19 with therapies approved to treat multiple sclerosis

There is growing concern that multiple sclerosis (MS) patients on certain therapies may be at higher risk for severe coronavirus disease 2019 (COVID-19). We conducted a systematic literature review to examine the available data on U.S. therapies approved to treat MS and the risk of SARS-CoV-2 infection or severe COVID-19 outcomes. We conducted searches in PubMed, Embase, and the WHO COVID-19 database through May 2, 2021, and retrieved articles describing clinical data on therapies approved to treat MS and the risk of infection with SARS-CoV-2 or the effects of such therapies on clinical outcomes of COVID-19. The literature search identified a total of 411 articles: 97 in PubMed, 227 in Embase, and 87 in the WHO database. After excluding duplicates and screening, we identified 15 articles of interest. We identified an additional article through a broader secondary weekly search in PubMed. Thus, ultimately, we reviewed 16 observational studies. Available data, which suggest that MS patients treated with anti-CD20 monoclonal antibodies may be at increased risk for severe COVID-19, are subject to relevant limitations. Generally, studies did not identify increased risk for COVID-19 worsening with other therapies approved to treat MS. Based on observational data, biological plausibility, novelty of the drug-event association, and public health implications in a subpopulation with potential impaired response to the COVID-19 vaccines, this safety signal merits further monitoring.