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• W3214636890 abstract "Introduction: B-cell depleting therapies used in multiple sclerosis (MS) have been associated with higher risk of severe COVID- 19. However, more precise knowledge of how B-cell depletion affects development of humoral and cellular immunity to viruses, in particular to SARS-CoV-2, is still limited. Objectives: To determine humoral and cellular SARS-CoV-2 responses after COVID-19 infection or vaccination in MS patients treated with different disease modulatory therapies (DMTs), with a focus on B-cell depleting therapies. Aims: Understand the impact of B-cell depleting therapy on the ability to develop a specific SARS-CoV-2 immunological memory after a COVID-19 infection or vaccination. Methods: We analyzed sera from subjects (n=2800) in an ongoing observational drug trial comprising multiple MS DMTs (COMBAT-MS;NCT03193866). In a single center subcohort (n=137, including healthy controls) enriched for COVID-19-like symptoms, samples for more detailed cellular analyses were obtained. Lastly, a small cohort of patients on B-cell depleting therapies were analyzed either before (n=4) or after (n=6) being vaccinated against SARS-CoV-2. Specific antibodies were determined with electro-chemiluminescence immunoassay and multiplex bead array. T-cell memory responses were determined by FluoroSpot and flow cytometry. Results: Data on humoral responses in the entire cohort will be included in the final presentation. The subcohort patients on B-cell depleting therapies were stratified into three different groups depending on B-cell status at onset of COVID-19-like symptoms;a) completely depleted ( 0.08;B-cell count x 10-9/L, n=3). Within the three groups, 50%/71%, 86%/100% and 100%/100% developed a SARS-CoV-2 specific antibody/T-cell response, respectively. Furthermore, antibody titers were not significantly different from those on other DMTs or healthy controls, and SARS-CoV-2 specific T-cells also displayed functional similarity. Lastly, in the vaccination cohort, all patients displayed a specific T-cell response after vaccination although only 50% of them also developed a humoral response. Conclusions: These findings indicate that B-cell depletion does not prevent a specific immunological memory after a COVID-19 infection or vaccination against SARS-CoV-2, and patients that do not develop humoral immunity might still have a specific T-cell response. Further studies are needed to determine the correlation between immunological parameters and clinical immunity." @default.
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• W3214636890 date "2021-01-01" @default.
• W3214636890 modified "2023-09-27" @default.
• W3214636890 title "Impact of B-cell depleting treatments on development of humoral and cellular immunological memory against SARS-CoV-2" @default.
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