Type of vaccine and immunosuppressive therapy but not diagnosis critically influence antibody response after COVID-19 vaccination in patients with rheumatic disease

Objective: The development of sufficient COVID-19 vaccines has been a big breakthrough in fighting the global SARS-CoV-2 pandemic. However, vaccination effectiveness can be reduced in patients with autoimmune rheumatic diseases (AIRD). The aim of this study was to identify factors that lead to a diminished humoral vaccination response in patients with AIRD. Methods: Vaccination response was measured with a surrogate virus neutralisation test and by testing for antibodies directed against the receptor-binding-domain (RBD) of SARS-CoV-2 in 308 fully vaccinated patients with AIRD. In addition, 296 immunocompetent participants were investigated as a control group. Statistical adjusted analysis included covariates with a possible influence on antibody response. Results: Patients with AIRD showed lower antibody responses compared with immunocompetent individuals (median neutralising capacity 90.8% vs 96.5%, p<0.001; median anti-RBD-IgG 5.6 S/CO vs 6.7 S/CO, p<0.001). Lower antibody response was significantly influenced by type of immunosuppressive therapy, but not by rheumatic diagnosis, with patients under rituximab therapy developing the lowest antibody levels. Patients receiving mycophenolate, methotrexate or janus kinase inhibitors also showed reduced vaccination responses. Additional negative influencing factors were vaccination with AZD1222, old age and shorter intervals between the first two vaccinations. Conclusion: Certain immunosuppressive therapies are associated with lower antibody responses after vaccination. Additional factors such as vaccine type, age and vaccination interval should be taken into account. We recommend antibody testing in at-risk patients with AIRD and emphasise the importance of booster vaccinations in these patients

Therapie der Syphilis

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SARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns

SARS-CoV-2 neutralizing antibodies play a critical role in COVID-19 prevention and treatment but are challenged by viral evolution and the emergence of novel escape variants. Importantly, the recently identified Omicron sublineages BA.2.12.1 and BA.4/5 are rapidly becoming predominant in various countries. By deter-mining polyclonal serum activity of 50 convalescent or vaccinated individuals against BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.4/5, we reveal a further reduction in BA.4/5 susceptibility to vaccinee sera. Most notably, delineation of sensitivity to an extended 163-antibody panel demonstrates pronounced antigenic differences with distinct escape patterns among Omicron sublineages. Antigenic distance and/or higher resistance may therefore favor immune-escape-mediated BA.4/5 expansion after the first Omicron wave. Finally, while most clinical-stage monoclonal antibodies are inactive against Omicron sublineages, we identify promising antibodies with high pan-SARS-CoV-2 neutralizing potency. Our study provides a detailed understanding of Omicron-sublineage antibody escape that can inform on effective strategies against COVID-19

Type of vaccine and immunosuppressive therapy but not diagnosis critically influence antibody response after COVID-19 vaccination in patients with rheumatic disease

Objective The development of sufficient COVID-19 vaccines has been a big breakthrough in fighting the global SARS-CoV-2 pandemic. However, vaccination effectiveness can be reduced in patients with autoimmune rheumatic diseases (AIRD). The aim of this study was to identify factors that lead to a diminished humoral vaccination response in patients with AIRD.Methods Vaccination response was measured with a surrogate virus neutralisation test and by testing for antibodies directed against the receptor-binding-domain (RBD) of SARS-CoV-2 in 308 fully vaccinated patients with AIRD. In addition, 296 immunocompetent participants were investigated as a control group. Statistical adjusted analysis included covariates with a possible influence on antibody response.Results Patients with AIRD showed lower antibody responses compared with immunocompetent individuals (median neutralising capacity 90.8% vs 96.5%, p&lt;0.001; median anti-RBD-IgG 5.6 S/CO vs 6.7 S/CO, p&lt;0.001). Lower antibody response was significantly influenced by type of immunosuppressive therapy, but not by rheumatic diagnosis, with patients under rituximab therapy developing the lowest antibody levels. Patients receiving mycophenolate, methotrexate or janus kinase inhibitors also showed reduced vaccination responses. Additional negative influencing factors were vaccination with AZD1222, old age and shorter intervals between the first two vaccinations.Conclusion Certain immunosuppressive therapies are associated with lower antibody responses after vaccination. Additional factors such as vaccine type, age and vaccination interval should be taken into account. We recommend antibody testing in at-risk patients with AIRD and emphasise the importance of booster vaccinations in these patients

Immunogenicity of COVID-19 Tozinameran Vaccination in Patients on Chronic Dialysis

Patients with kidney failure have notoriously weak responses to common vaccines. Thus, immunogenicity of novel SARS-CoV-2 vaccines might be impaired in this group. To determine immunogenicity of SARS-CoV-2 vaccination in patients with chronic dialysis, we analyzed the humoral and T-cell response after two doses of mRNA vaccine Tozinameran (BNT162b2 BioNTech/Pfizer). This observational study included 43 patients on dialysis before vaccination with two doses of Tozinameran 21 days apart. Overall, 36 patients completed the observation period until three weeks after the second dose and 32 patients were further analyzed at week 10. Serum samples were analyzed by SARS-CoV-2 specific IgG and IgA antibodies ~1, ~3-4 and ~10 weeks after the second vaccination. In addition, SARS-CoV-2-specific T-cell responses were assessed at ~3-4 weeks by an interferon-gamma release assay (IGRA). Antibody and T cell outcomes at this timepoint were compared to a group of 44 elderly patients not on dialysis, after immunization with Tozinameran. Median age of patients on chronic dialysis was 74.0 years (IQR 66.0, 82.0). The proportion of males was higher (69.4%) than females. Only 20/36 patients (55.6%, 95%CI: 38.29-71.67) developed SARS-CoV-2-IgG antibodies at the first sampling, whereas 32/36 patients (88.9%, 95%CI: 73.00-96.38) demonstrated IgG detection at the second sampling. In a longitudinal follow-up at ~10 weeks after the second dose, the proportion of dialysis patients reactive for anti-SARS-CoV-2-IgG decreased to 27/32 (84.37%, 95%CI: 66.46-94.10) The proportion of anti-SARS-CoV-2 S1 IgA decreased from 33/36 (91.67%; 95%CI: 76.41-97.82) at weeks 3-4 down to 19/32 (59.38; 95%CI: 40.79-75.78). Compared to a cohort of vaccinees with similar age but not on chronic dialysis seroconversion rates and antibody titers were significantly lower. SARS-CoV-2-specific T-cell responses 3 weeks after second vaccination were detected in 21/31 vaccinated dialysis patients (67.7%, 95%CI: 48.53-82.68) compared to 42/44 (93.3%, 95%CI: 76.49-98.84) in controls of similar age. Patients on dialysis demonstrate a delayed, but robust immune response three to four weeks after the second dose, which indicates effective vaccination of this vulnerable group. However, the lower immunogenicity of Tozinameran in these patients needs further attention to develop potential countermeasures such as an additional booster vaccination