Development of humoral and cellular immunological memory against SARS-CoV-2 despite B cell depleting treatment in multiple sclerosis.

B cell depleting therapies (BCDTs) are widely used as immunomodulating agents for autoimmune diseases such as multiple sclerosis. Their possible impact on development of immunity to severe acute respiratory syndrome virus-2 (SARS-CoV-2) has raised concerns with the coronavirus disease 2019 (COVID-19) pandemic. We here evaluated the frequency of COVID-19-like symptoms and determined immunological responses in participants of an observational trial comprising several multiple sclerosis disease modulatory drugs (COMBAT-MS; NCT03193866) and in eleven patients after vaccination, with a focus on BCDT. Almost all seropositive and 17.9% of seronegative patients on BCDT, enriched for a history of COVID-19-like symptoms, developed anti-SARS-CoV-2 T cell memory, and T cells displayed functional similarity to controls producing IFN-γ and TNF. Following vaccination, vaccine-specific humoral memory was impaired, while all patients developed a specific T cell response. These results indicate that BCDTs do not abrogate SARS-CoV-2 cellular memory and provide a possible explanation as to why the majority of patients on BCDTs recover from COVID-19.

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© 2021 The Author(s).

Déclaration de conflit d'intérêts

T.O. has received unrestricted grants for extended multiple sclerosis studies in relation to COVID-19 from Biogen and Merck. Not related to this manuscript, T.O. has received unrestricted grants, advisory board/ lectures from Biogen, Merck, Novartis, and Sanofi, and F.P. has received research grants from Genzyme, Merck KGaA, and UCB and fees for serving as Chair of DMC in clinical trials with Parexel. All other authors declare no competing interests.