ABSTRACT
Objectives Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are overlapping autoinflammatory diseases affecting people over 50 years. The diseases are treated with immunosuppressive drugs such as prednisolone, methotrexate, leflunomide and tocilizumab. In this study, we assessed the immunogenicity and safety of SARS-CoV-2 vaccinations in these diseases (based on humoral and cellular immunity). Methods Patients (n=45 GCA, n=33 PMR) visited the outpatient clinic twice: pre-vaccination and 4 weeks after the second dose (BNT162b2 or ChAdOx1 vaccine). Patients with previous SARS-CoV-2 infection were excluded. In both pre-vaccination and post-vaccination samples, anti-Spike antibody concentrations were assessed and compared with age-, sex-and vaccine-matched control groups (n=98). In addition, the frequency of SARS-CoV-2 Spike-specific T-cells was assessed by IFN-gammaELIspot assay, and side effects and disease activity were recorded. Results GCA/PMR patients did not have reduced antibody concentrations compared with controls. However, linear regression analysis revealed a significant association of methotrexate and >10 mg/day prednisolone use with lower antibody concentrations in GCA/PMR patients. Evidence of cellular immunity, as assessed by ELIspot assay, was found in 67% of GCA/PMR patients. Patients using >10 mg/day prednisolone had reduced cellular immunity. Importantly, vaccination did not lead to significant side effects or changes in disease activity. Conclusions SARS-CoV-2 vaccination was safe for GCA/PMR patients and immunogenicity was comparable to other older individuals. However, patients using methotrexate and particularly >10 mg/day prednisolone did show lower vaccine responses, which corroborates findings in other autoinflammatory patient populations. These patients may therefore be at higher risk of (potentially even severe) breakthrough SARS-CoV-2 infection. Copyright ©
ABSTRACT
Purpose: Torque tenovirus (TTV), a highly prevalent virus which is not known to cause pathology in humans, is currently being investigated as a marker of immunosuppression. In this study we investigated if the TTV load measured prior to COVID-19 vaccination can predict the serological response to the COVID-19 vaccine, measured 28 days after the second vaccination dose. Method(s): The humoral response to the mRNA 1273 vaccine (Moderna) was assessed in Lung transplant recipients (LTR) who received a transplant between 4 and 237 months prior, by measuring Spike-specific IgG levels at 28 days after the second vaccination. Antibody concentrations of >10 BAU/ml were considered reactive. TTV loads were determined by PCR and Pearson's correlation coefficient was calculated to correlate serological responses to TTV load. Patient characteristics, including reasons for transplantation, antirejection treatment, age and time since transplantation, were recorded to assess associations between these factors and vaccination response or TTV levels. Result(s): 103 LTR were included of which 41 (40%) showed some response (>10 BAU/ml) to the vaccine at 28 days after the second vaccination. 61 (60%) were non-responders. TTV loads at baseline varied between negative and 10E9 copies/ ml. The TTV loads were found to correlate with IgG levels and the with the percentage of responders 28 days after the second vaccination (=<0.001). TTV loads also correlated strongly with the time since transplantation. High TTV levels occurred predominantly in patients who were shorter after transplantation (p=0.0001). Conclusion(s): This study shows an association between pre-vaccination TTV load and humoral response to the SARS-CoV-2 vaccine, which correlate with the time after transplantation. We recommend that TTV load measurements are included in further vaccination efficacy studies in immunocompromised cohorts. If the TTV load is indeed a predictor of vaccine response, this could be used as a potential guidance for optimizing vaccination response.
ABSTRACT
Background: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are overlapping autoinfammatory diseases affecting people over 50 years. The diseases are treated with immunosuppressive drugs such as prednisolone, metho-trexate, lefunomide and tocilizumab. Even though GCA and PMR patients have a substantially higher risk for infections, little is known about humoral and cellular immune responses after vaccination in these patients. Objectives: In this study we assessed the immunogenicity and safety of SARS-CoV-2 vaccinations in these diseases. Methods: Patients (n=45 GCA, n=33 PMR) visited the outpatient clinic twice: pre-vaccination and 4 weeks post-vaccination (BNT162b2 or ChAdOx1 vaccine). Patients with previous SARS-CoV-2 infection were excluded. In both pre-and post-vaccination samples, anti-Spike antibody concentrations were assessed and compared to age-, sex-and vaccine-matched control groups (n=98). In addition, the frequency of SARS-CoV-2 Spike-specifc T-cells was assessed by IFN-γ ELIspot assay, and side-effects and disease activity were recorded. Results: The GCA/PMR patients, as a group, did not have reduced antibody concentrations compared to controls. However, linear regression analysis revealed a signifcant association of methotrexate and >10mg/day prednisolone use with lower antibody concentrations in GCA/PMR patients. Evidence of cellular immunity, as assessed by ELIspot assay, was found in 67% of GCA/PMR patients, and was correlated with humoral immunity (Figure 1). Patients using >10mg/day prednisolone had reduced cellular immunity. Importantly, vaccination did not lead to signifcant side-effects or changes in disease activity. Conclusion: SARS-CoV-2 vaccination was safe for GCA/PMR patients and immunogenicity was comparable to other older individuals. However, patients using methotrexate and particularly >10mg/day prednisolone did show lower vaccine responses, which corroborates fndings in other autoinfammatory patient populations. These patients may therefore be at higher risk of (potentially even severe) breakthrough SARS-CoV-2 infection.
ABSTRACT
Background: Patients with cancer have an increased risk of complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Vaccination is recommended, but the impact of chemotherapy and immunotherapy on immunogenicity and safety is still unclear. Methods: This prospective multicenter non-inferiority trial comprises four cohorts: individuals without cancer (A) and patients with solid tumors who were treated with immunotherapy (B), chemotherapy (C) or chemo-immunotherapy (D). Participants received two mRNA-1273 vaccinations 28 days apart. The primary endpoint was SARS-CoV-2 Spike S1-specific IgG serum antibody response, defined as >10 binding antibody units (BAU)/ml 28 days after the second vaccination. We also assessed the virus neutralizing capacity of these antibodies, SARS-CoV-2 Spike-specific interferon-gamma T cell response, and adverse events. Results: Of the 791 participants enrolled, 743 were evaluable for the primary endpoint in cohort A (n=240), B (n=131), C (n=229) and D (n=143). A SARS-CoV-2-binding antibody response was found in 100%, 99.3%, 97.4%, and 100% of the participants in cohorts A, B, C, and D, respectively. To discriminate between suboptimal and adequate responders, we defined a cut-off level at 300 BAU/ml, based on neutralizing capacity. The antibody response was considered adequate after the first vaccination in 66.0%, 37.1%, 32.5%, and 33.3% of the participants in cohorts A, B, C, and D, respectively. This raised 28 days after the second vaccination to respectively 99.6%, 93.1%, 83.8%, and 88.8% in cohorts A, B, C, and D. Spike-specific T cell responses were detected in 46.7% of suboptimal and non-responders. No new safety signals were observed. Conclusions: mRNA-1273 vaccination is safe in the patient populations studied. For each cohort, the proportion of patients with a SARS-CoV-2-binding antibody response after two vaccinations is non-inferior compared to individuals without cancer. However, a significant minority lacks an adequate response. Most patients have an antibody concentration increase after the second vaccination. Therefore, an additional booster may turn inadequate into adequate responders. Clinical trial identification: NCT04715438. Legal entity responsible for the study: University Medical Center Groningen, the Netherlands. Funding: ZonMw, The Netherlands Organisation for Health Research and Development. Disclosure: All authors have declared no conflicts of interest.