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Development of Humoral and Cellular Immunological Memory Against SARS-CoV-2 Despite B-Cell Depleting Treatment in Multiple Sclerosis

102 Pages Posted: 2 Mar 2021 Publication Status: Review Complete

See all articles by Klara Asplund Högelin

Klara Asplund Högelin

Karolinska Institutet - Neuroimmunology Unit

Nicolas Ruffin

Karolinska Institutet - Neuroimmunology Unit

Elisa Pin

KTH Royal Institute of Technology - Division of Affinity Proteomics

Anna Månberg

KTH Royal Institute of Technology - Division of Affinity Proteomics

Sophia Hober

KTH Royal Institute of Technology - Division of Protein Technology

Guro Gafvelin

Karolinska Institutet - Therapeutic Immune Design Unit

Hans Grönlund

Karolinska Institutet - Therapeutic Immune Design Unit

Peter Nilsson

KTH Royal Institute of Technology - Division of Affinity Proteomics

Mohsen Khademi

Karolinska Institutet - Neuroimmunology Unit

Tomas Olsson

Karolinska Institutet - Neuroimmunology Unit

Fredrik Piehl

Karolinska Institutet - Neuroimmunology Unit

Faiez Al Nimer

Karolinska Institutet - Neuroimmunology Unit

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Abstract

B-cell depleting therapies are widely used as immunomodulating agents for autoimmune diseases such as multiple sclerosis. The possible impact of B-cell depletion on development of humoral and cellular immunity to viruses and specifically SARS-CoV-2 has raised concerns with the COVID-19 pandemic. We here determined humoral and cellular responses in participants of an observational trial comprising several multiple sclerosis disease modulatory drugs (COMBAT-MS; NCT03193866). Patients on B-cell depleting treatment, who previously had COVID-19-like symptoms, developed anti-SARS-CoV-2 antibodies and/or T-cell memory irrespective of their B-cell depletion status. Furthermore, antibody titers were similar to those observed with other treatments or controls, and anti-SARS-CoV-2 T-cells displayed functional similarity to controls producing IFN-γ and TNF. These results inform on the role of B- and T-cells in SARS-CoV-2 immunity and provide evidence that B-cell depleting therapy does not substantially abrogate SARS-CoV-2 immunological memory, in turn suggesting a low risk for reinfection and potentially responsiveness to vaccination.

Funding: The COMBAT-MS study is funded through a Patient-Centered Outcomes Research Institute (PCORI) Award (MS-1511-33196), modified to include the sub-study reported herein. Additional funding was obtained from the Swedish Medical Research council (grant no. 2017-03054), Swedish Brain Foundation, NEURO Sweden, Tetra Laval, Region Stockholm, Knut and Alice Wallenberg foundation, Erling-Persson family foundation and Petrus och Augusta Hedlunds Stiftelse.

Conflict of Interest: Tomas Olsson has received unrestricted grants for extended multiplesclerosis 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.

Ethical Approval: Study procedures were conducted under the following ethical permits approved by the Swedish ethical review authority; COMBAT-MS: 2017/32-31/4; STOPMSII: 2009/2107-31/2; 2020 00052, with written informed consent from participants.

Keywords: [comma separated]SARS-CoV-2, COVID-19, B-cells, T-cells, humoral memory, cellular memory, multiple sclerosis, B-cell depletion, rituximab

Suggested Citation

Asplund Högelin, Klara and Ruffin, Nicolas and Pin, Elisa and Månberg, Anna and Hober, Sophia and Gafvelin, Guro and Grönlund, Hans and Nilsson, Peter and Khademi, Mohsen and Olsson, Tomas and Piehl, Fredrik and Al Nimer, Faiez, Development of Humoral and Cellular Immunological Memory Against SARS-CoV-2 Despite B-Cell Depleting Treatment in Multiple Sclerosis. Available at SSRN: https://ssrn.com/abstract=3796531 or http://dx.doi.org/10.2139/ssrn.3796531
This version of the paper has not been formally peer reviewed.

Klara Asplund Högelin

Karolinska Institutet - Neuroimmunology Unit ( email )

Sweden

Nicolas Ruffin

Karolinska Institutet - Neuroimmunology Unit ( email )

Sweden

Elisa Pin

KTH Royal Institute of Technology - Division of Affinity Proteomics ( email )

Anna Månberg

KTH Royal Institute of Technology - Division of Affinity Proteomics ( email )

Sophia Hober

KTH Royal Institute of Technology - Division of Protein Technology ( email )

Guro Gafvelin

Karolinska Institutet - Therapeutic Immune Design Unit ( email )

Granits väg 4
Section for Integrative Physiology
Solna, Stockholm 17171
Sweden

Hans Grönlund

Karolinska Institutet - Therapeutic Immune Design Unit ( email )

Granits väg 4
Section for Integrative Physiology
Solna, Stockholm 17171
Sweden

Peter Nilsson

KTH Royal Institute of Technology - Division of Affinity Proteomics

Mohsen Khademi

Karolinska Institutet - Neuroimmunology Unit ( email )

Sweden

Tomas Olsson

Karolinska Institutet - Neuroimmunology Unit ( email )

Sweden

Fredrik Piehl

Karolinska Institutet - Neuroimmunology Unit ( email )

Sweden

Faiez Al Nimer (Contact Author)

Karolinska Institutet - Neuroimmunology Unit ( email )

Sweden

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