ABSTRACT
Disease-modifying therapies (DMTs) impact the cellular immune response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (pwMS). In this study, we aim to elucidate the characteristics of the involved antigen-specific T cells via the measurement of broad cytokine profiles in pwMS on various DMTs. We examined SARS-CoV-2-specific T cell responses in whole blood cultures characterized by the release of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-13, IL-17A, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), as well as antibodies (AB) targeting the SARS-CoV-2 spike protein in pwMS following either two or three doses of mRNA or viral vector vaccines (VVV). For mRNA vaccination non-responders, the NVX-CoV2373 protein-based vaccine was administered, and immune responses were evaluated. Our findings indicate that immune responses to SARS-CoV-2 vaccines in pwMS are skewed towards a Th1 phenotype, characterized by IL-2 and IFN-γ. Additionally, a Th2 response characterized by IL-5, and to a lesser extent IL-4, IL-10, and IL-13, is observed. Therefore, the measurement of IL-2 and IL-5 levels could complement traditional IFN-γ assays to more comprehensively characterize the cellular responses to SARS-CoV-2 vaccines. Our results provide a comprehensive cytokine profile for pwMS receiving different DMTs and offer valuable insights for designing vaccination strategies in this patient population.
ABSTRACT
Our objective was to analyze longitudinal cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in people with multiple sclerosis (pwMS) on B-cell depleting treatment (BCDT) compared to pwMS without immunotherapy. We further evaluated the impact of COVID-19 infection and vaccination timing. PwMS (n = 439) on BCDT (ocrelizumab, rituximab, ofatumumab) or without immunotherapy were recruited for this prospective cohort study between June 2021 and June 2022. SARS-CoV-2 spike-specific antibodies and interferon-γ release of CD4 and CD8 T-cells upon stimulation with spike protein peptide pools were analyzed at different timepoints (after primary vaccination, 3 and 6 months after primary vaccination, after booster vaccination, 3 months after booster). Humoral response to SARS-CoV-2 was consistently lower whereas T-cell response was higher in patients with BCDT compared to controls. Cellular and humoral responses decreased over time after primary vaccination and increased again upon booster vaccination, with significantly higher antibody titers after booster than after primary vaccination in both untreated and B-cell-depleted pwMS. COVID-19 infection further led to a significant increase in SARS-CoV-2-specific responses. Despite attenuated B-cell responses, a third vaccination for patients with BCDT seems recommendable, since at least partial protection can be expected from the strong T-cell response. Moreover, our data show that an assessment of T-cell responses may be helpful in B-cell-depleted patients to evaluate the efficacy of SARS-CoV-2 vaccination.
ABSTRACT
BACKGROUND: Total hip arthroplasty (THA) is associated with substantial blood loss in the postoperative course. Tranexamic acid (TXA) is a potent antifibrinolytic agent, routinely administered by intravenous (IV) and topical (intra-articular, IA) route, which can possibly interrupt the cascade of events due to hemostatic irregularities close to the source of bleeding. However, scientific evidence of combined administration of TXA in THA secondary to a femoral neck fracture is still meagre. The present study aims to compare the patients who were administered combined IV and topical TXA with a control group in terms of blood loss, transfusion rate, and incidence of deep vein thrombosis (DVT) and thromboembolism (TE). Patients and Methods. 195 patients with femoral neck fracture underwent THA and were placed into two groups: (1) IV and IA TXA group which had 58 patients and (2) no TXA control group which had 137 patients. In the TXA group, 1 g IV TXA was administered 30 minutes before incision, and 1 g IA TXA was administered intraoperatively after fascia closure. No drains were placed, and soft spica was applied to the hip. RESULTS: Combined usage of IV and IA TXA showed better results when compared to the control group in terms of blood transfusion rate (31%) and hemoglobin drop (28%). No cases of DVT or TE were noted among the two study groups. CONCLUSION: Combined use of IV and IA TXA provided significantly better results compared to no TXA use with respect to all variables related to postoperative blood loss in THA. Moreover, TXA use is safe in terms of incidence of symptomatic DVT and TE.
