Development of humoral and cellular immunological memory against SARS-CoV-2 despite B cell depleting treatment in multiple sclerosis
Klara Asplund Högelin,
Nicolas Ruffin,
Elisa Pin,
Anna Månberg,
Sophia Hober,
Guro Gafvelin,
Hans Grönlund,
Peter Nilsson,
Mohsen Khademi,
Tomas Olsson,
Fredrik Piehl,
Faiez Al Nimer
Affiliations
Klara Asplund Högelin
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine L8:04, 171 76 Stockholm, Sweden
Nicolas Ruffin
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine L8:04, 171 76 Stockholm, Sweden
Elisa Pin
Division of Affinity Proteomics, Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, 17165 Stockholm, Sweden
Anna Månberg
Division of Affinity Proteomics, Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, 17165 Stockholm, Sweden
Sophia Hober
Division of Protein Technology, Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, 17165 Stockholm, Sweden
Guro Gafvelin
Therapeutic Immune Design Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine L8:02, 171 76 Stockholm, Sweden
Hans Grönlund
Therapeutic Immune Design Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine L8:02, 171 76 Stockholm, Sweden
Peter Nilsson
Division of Affinity Proteomics, Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, 17165 Stockholm, Sweden
Mohsen Khademi
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine L8:04, 171 76 Stockholm, Sweden
Tomas Olsson
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine L8:04, 171 76 Stockholm, Sweden
Fredrik Piehl
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine L8:04, 171 76 Stockholm, Sweden
Faiez Al Nimer
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine L8:04, 171 76 Stockholm, Sweden; Corresponding author
Summary: 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.
