@article {R{\"a}uberjnnp-2021-328197, author = {Saskia R{\"a}uber and Melanie Korsen and Niklas Huntemann and Leoni Rolfes and Thomas M{\"u}ntefering and Vera Dobelmann and Alexander M Hermann and Tristan K{\"o}lsche and Karin von Wnuck Lipinski and Christina B Schroeter and Christopher Nelke and Liesa Regner-Nelke and Jens Ingwersen and Marc Pawlitzki and Bianca Teegen and Michael Harry Barnett and Hans-Peter Hartung and Orhan Aktas and Philipp Albrecht and Bodo Levkau and Nico Melzer and Tobias Ruck and Sven G Meuth and David Kremer}, title = {Immune response to SARS-CoV-2 vaccination in relation to peripheral immune cell profiles among patients with multiple sclerosis receiving ocrelizumab}, elocation-id = {jnnp-2021-328197}, year = {2022}, doi = {10.1136/jnnp-2021-328197}, publisher = {BMJ Publishing Group Ltd}, abstract = {Background Vaccination has proven to be effective in preventing SARS-CoV-2 transmission and severe disease courses. However, immunocompromised patients have not been included in clinical trials and real-world clinical data point to an attenuated immune response to SARS-CoV-2 vaccines among patients with multiple sclerosis (MS) receiving immunomodulatory therapies.Methods We performed a retrospective study including 59 ocrelizumab (OCR)-treated patients with MS who received SARS-CoV-2 vaccination. Anti-SARS-CoV-2-antibody titres, routine blood parameters and peripheral immune cell profiles were measured prior to the first (baseline) and at a median of 4 weeks after the second vaccine dose (follow-up). Moreover, the SARS-CoV-2-specific T cell response and peripheral B cell subsets were analysed at follow-up. Finally, vaccination-related adverse events were assessed.Results After vaccination, we found anti-SARS-CoV-2(S) antibodies in 27.1\% and a SARS-CoV-2-specific T cell response in 92.7\% of MS cases. T cell-mediated interferon (IFN)-γ release was more pronounced in patients without anti-SARS-CoV-2(S) antibodies. Antibody titres positively correlated with peripheral B cell counts, time since last infusion and total IgM levels. They negatively correlated with the number of previous infusion cycles. Peripheral plasma cells were increased in antibody-positive patients. A positive correlation between T cell response and peripheral lymphocyte counts was observed. Moreover, IFN-γ release was negatively correlated with the time since the last infusion.Conclusion In OCR-treated patients with MS, the humoral immune response to SARS-CoV-2 vaccination is attenuated while the T cell response is preserved. However, it is still unclear whether T or B cell-mediated immunity is required for effective clinical protection. Nonetheless, given the long-lasting clinical effects of OCR, monitoring of peripheral B cell counts could facilitate individualised treatment regimens and might be used to identify the optimal time to vaccinate.Data are available upon reasonable request. Further information and requests for resources and anonymised clinical data should be directed to and will be fulfilled by David Kremer (DavidMaxJoe.Kremer@med.uni-duesseldorf.de)}, issn = {0022-3050}, URL = {https://jnnp.bmj.com/content/early/2022/02/21/jnnp-2021-328197}, eprint = {https://jnnp.bmj.com/content/early/2022/02/21/jnnp-2021-328197.full.pdf}, journal = {Journal of Neurology, Neurosurgery \& Psychiatry} }