ABSTRACT
Objective: To investigate the humoral and T-cell immune response of multiple sclerosis (MS) patients under B-cell depleting therapy following SARS-CoV-2 vaccination compared to healthy controls (HC). Background: The SARS-CoV-2 pandemic has huge implications for the management of patients with MS under highly active immune therapies. First reports indicated that the humoral response of anti-CD20 treated, B-cell depleted patients might by attenuated. Data about dynamics of B-cell repopulation and T-cell response are scarce. Design/Methods: The study was authorized by the local ethics committee of the RuhrUniversity Bochum. Patients were recruited at the Department of Neurology. We included n=10 healthy age-matched controls and n=37 B-cell depleted MS patients (20 ocrelizumab, 17 off-label rituximab). Serum and Peripheral Blood Mononuclear Cells (PBMCs) were isolated 4-8 weeks after second vaccination. Serum was analyzed for anti-SARS-CoV-2-Spike antibodies. Lymphocyte subpopulations were analyzed in B-cell depleted patients by FACS analysis. PBMCs were stimulated with 2 μg/ml SARS-CoV-2 peptide-mix for 16-18 hours and analyzed via flow cytometry for cytokine-expressing T-cell populations. Results: 15/36 (40.5%) patients mounted an antibody response >10 U/ml (range 0.8-2,500). The anti-SARS-CoV-2-Spike titer correlated with B-cell repopulation (R2 =0.01841;r=0.4481;p=0.0069), whereas no significance could be detected correlating with the time to last infusion (R2 =0.1352;r=0.3058;p=0.0740). On the contrary, T-cell responses of B-cell depleted patients were higher or did not deviate from those of HC. Frequencies of CD4+ -T-cells expressing IFN-γ or IL-4 and CD8+ -T-cells expressing IFN-γ or IFN-γ and IL-2 were significantly higher in B-cell depleted patients, while CD4+ -T-cells expressing IL-2 or IFN-γ and IL-2 as well as CD8+ -T-cells expressing IL-2 did not differ from HC. Conclusions: Humoral vaccination responses in B-cell depleted patients are dependent on B-cell repopulation. Notably, patients with poor humoral response are able to mount a sustained T-cell response after SARS-CoV-2 vaccination. Those data suggest, that vaccinated B-cell depleted patients might be partially protected against SARS-CoV-2 infection.
ABSTRACT
Objective: To characterize the incidence and spectrum of neurological adverse events (AE) after COVID-19 vaccination. Background: The devastating COVID-19 pandemic has led to 230 million people diagnosed and greater than 4.8 million deaths worldwide. Widespread vaccination efforts have resulted in administration of over 6 million vaccine doses to curb the significant health and socioeconomic impacts of the disease. While there are numerous reports of adverse events following COVID-19 vaccine, there is limited characterization of the spectrum of neurological AEs post-vaccination. Design/Methods: Data was gathered from the publicly available Vaccine Adverse Event Reporting System (VAERS), a passive reporting system not implying causality. Among individuals who received the J&J, Moderna, and Pfizer vaccines from 1/1/2021-6/14/2021, 314,610 adverse events were reported and these were reviewed by Neurology trained clinicians to determine the presence of various neurological AEs (40 conditions coded). Results: 306,473,169 COVID vaccine dose were administered in the USA during the study period with 314,610 total AEs (0.10%) and 105,930 neurological AEs (0.03%) reported. J&J vaccine was associated with the most AEs (17,670, 0.15%), followed by Moderna (42656, 0.03%) and Pfizer (42267, 0.03%). On average more events were reported in women (71%) and a majority occurred after the first dose (54%). < 1 events were reported per million vaccine doses for serious neurological conditions such as Bell's palsy (0.0007%), Guillain-Barre syndrome (0.00009%), cerebral venous thrombosis (0.00005%), transverse myelitis (0.00003%), and acute disseminated encephalomyelitis (0.00006%). Overall neurological complications following vaccine were drastically lower than complications post-COVID infection (14-80%). Conclusions: Adverse neurological events following COVID-19 vaccination are extremely rare and significantly less common than adverse neurological effects following SARS-CoV-2 infection. Current evidence suggests that along with being up to 100,000 times more likely to experience a major complication from COVID infection vs. vaccine, the risk of neurological complication is up to 5000 times more likely from infection itself.