Serological Response to BNT162b2 Anti-SARS-CoV-2 Vaccination in Patients with Inflammatory Rheumatic Diseases: Results From the RHEUVAX Cohort

Mauro, Daniele; Ciancio, Antonio; Vico, Claudio Di; Passariello, Luana; Rozza, Gelsomina; Pasquale, Maria Dora; Pantano, Ilenia; Cannistrà, Carlo; Bucci, Laura; Scriffignano, Silvia; Riccio, Flavia; Patrone, Martina; Scalise, Giuseppe; Ruscitti, Piero; Montemurro, Maria Vittoria; Giordano, Antonio; Vietri, Maria Teresa; Ciccia, Francesco

doi:10.3389/fimmu.2022.901055

Cited by 12 publications

(12 citation statements)

References 53 publications

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“…No pilot studies have been performed either by us or other authors, considering the single groups of immunosuppressed patients: according to biostatistical methods, pilot studies were not performed with limited numbers of cases, because this does not allow to make inferences between data. Although preliminary, much data is accumulating from different groups [25,26,48,49] identifying Aba as a negative predictor of response to SARS-CoV2 vaccination, confirming our data. Wider and multicenter studies should be advisable to overcome the limitation of the small sample size.…”

Section: Discussionsupporting

confidence: 87%

“…This sample size is comparable to other papers published by different groups [25,26,45,48], including a recent case-control study [49], all demonstrating a reduced cellular response by Aba-treated patients and reduced seroconversion rate in RTX-treated patients. No pilot studies have been performed either by us or other authors, considering the single groups of immunosuppressed patients: according to biostatistical methods, pilot studies were not performed with limited numbers of cases, because this does not allow to make inferences between data.…”

Section: Discussionsupporting

confidence: 86%

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Efficacy of COVID-19 mRNA vaccination in patients with autoimmune disorders: humoral and cellular immune response

Filippini

Giacomelli

Bazzani

et al. 2023

BMC Med

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Background The impact of immunosuppressive therapies on the efficacy of vaccines to SARS-CoV-2 is not completely clarified. We analyzed humoral and T cell-mediated response after COVID-19 mRNA vaccine in immunosuppressed patients and patients with common variable immunodeficiency disease (CVID). Patients We enrolled 38 patients and 11 healthy sex- and age-matched controls (HC). Four patients were affected by CVID and 34 by chronic rheumatic diseases (RDs). All patients with RDs were treated by corticosteroid therapy and/or immunosuppressive treatment and/or biological drugs: 14 patients were treated with abatacept, 10 with rituximab, and 10 with tocilizumab. Methods Total antibody titer to SARS-CoV-2 spike protein was assessed by electrochemiluminescence immunoassay, CD4 and CD4-CD8 T cell-mediated immune response was analyzed by interferon-γ (IFN-γ) release assay, the production of IFN-γ-inducible (CXCL9 and CXCL10) and innate-immunity chemokines (MCP-1, CXCL8, and CCL5) by cytometric bead array after stimulation with different spike peptides. The expression of CD40L, CD137, IL-2, IFN-γ, and IL-17 on CD4 and CD8 T cells, evaluating their activation status, after SARS-CoV-2 spike peptides stimulation, was analyzed by intracellular flow cytometry staining. Cluster analysis identified cluster 1, namely the “high immunosuppression” cluster, and cluster 2, namely the “low immunosuppression” cluster. Results After the second dose of vaccine, only abatacept-treated patients, compared to HC, showed a reduced anti-spike antibody response (mean: 432 IU/ml ± 562 vs mean: 1479 IU/ml ± 1051: p = 0.0034), and an impaired T cell response, compared with HC. In particular, we found a significantly reduced release of IFN-γ from CD4 and CD4-CD8 stimulated T cells, compared with HC (p = 0.0016 and p = 0.0078, respectively), reduced production of CXCL10 and CXCL9 from stimulated CD4 (p = 0.0048 and p = 0.001) and CD4-CD8 T cells (p = 0.0079 and p = 0.0006). Multivariable General Linear Model analysis confirmed a relationship between abatacept exposure and impaired production of CXCL9, CXCL10, and IFN-γ from stimulated T cells. Cluster analysis confirms that cluster 1 (including abatacept and half of rituximab treated cases) showed a reduced IFN-γ response, as well as reduced monocyte-derived chemokines All groups of patients demonstrated the ability to generate specific CD4 T activated cells after spike proteins stimulation. After the third dose of vaccine, abatacept-treated patients acquired the ability to produce a strong antibody response, showing an anti-S titer significantly higher compared to that obtained after the second dose (p = 0.0047), and comparable with the anti-S titer of the other groups. Conclusions Patients treated with abatacept showed an impaired humoral immune response to two doses of COVID-19 vaccine. The third vaccine dose has been demonstrated to be useful to induce a more robust antibody response to balance an impaired T cell-mediated one. All patients, exposed to different immunosuppressive drugs, were able to produce specific CD4-activated T cells, after spike proteins stimulation. Trial registration Local Ethical Committee NP4187.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 86%

Efficacy of COVID-19 mRNA vaccination in patients with autoimmune disorders: humoral and cellular immune response

Filippini

Giacomelli

Bazzani

et al. 2023

BMC Med

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“…The negative impact of rituximab on vaccines' immunogenicity has been demonstrated for many vaccines before the arrival of COVID-19 vaccines (27-29). Despite the differences in dosage and timing of drug administration, most patients who required repeated courses of rituximab treatment, including those with IMDD, have struggled to mount humoral immunity following COVID-19 vaccines (8,9,20,(30)(31)(32). Attempts to rectify the situation by using more-immunogenic vaccine platforms (e.g., mRNA and viral vector technologies), lowering rituximab dose, or giving additional vaccine doses have not shown promising benefits (32)(33)(34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Optimal time for COVID-19 vaccination in rituximab-treated dermatologic patients

Seree-aphinan

Ratanapokasatit²,

Suchonwanit³

et al. 2023

Front. Immunol.

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BackgroundBy depleting circulating B lymphocytes, rituximab time-dependently suppresses coronavirus disease 2019 (COVID-19) vaccines’ humoral immunogenicity for a prolonged period. The optimal time to vaccinate rituximab-exposed immune-mediated dermatologic disease (IMDD) patients is currently unclear.ObjectiveTo estimate the vaccination timeframe that equalized the occurrence of humoral immunogenicity outcomes between rituximab-exposed and rituximab-naïve IMDD patients.MethodsThis retrospective cohort study recruited rituximab-exposed and age-matched rituximab-naïve subjects tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunity post-vaccination. Baseline clinical and immunological data (i.e., immunoglobulin levels, lymphocyte immunophenotyping) and SARS-CoV-2-specific immunity levels were extracted. The outcomes compared were the percentages of subjects who produced neutralizing antibodies (seroconversion rates, SR) and SARS-CoV-2-specific IgG levels among seroconverters. The outcomes were first analyzed using multiple regressions adjusted for the effects of corticosteroid use, steroid-spearing agents, and pre-vaccination immunological status (i.e., IgM levels, the percentages of the total, naïve, and memory B lymphocytes) to identify rituximab-related immunogenicity outcomes. The rituximab-related outcome differences with a 95% confidence interval (CI) between groups were calculated, starting by including every subject and then narrowing down to those with longer rituximab-to-vaccination intervals (≥3, ≥6, ≥9, ≥12 months). The desirable cut-off performances were <25% outcome inferiority observed among rituximab-exposed subgroups compared to rituximab-naïve subjects, and the positive likelihood ratio (LR+) for the corresponding outcomes ≥2.FindingsForty-five rituximab-exposed and 90 rituximab-naive subjects were included. The regression analysis demonstrated a negative association between rituximab exposure status and SR but not with SARS-CoV-2-specific IgG levels. Nine-month rituximab-to-vaccination cut-off fulfilled our prespecified diagnostic performance (SR difference between rituximab-exposed and rituximab-naïve group [95%CI]: -2.6 [-23.3, 18.1], LR+: 2.6) and coincided with the repopulation of naïve B lymphocytes in these patients.ConclusionsNine months of rituximab-to-vaccination interval maximize the immunological benefits of COVID-19 vaccines while avoiding unnecessary delay in vaccination and rituximab treatment for IMDD patients.

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“…The role of treatments and, in particular, rituximab has been confirmed in the same way as for other vaccines. Seroconversion has also been described as impaired in patients with auto-immune diseases treated with rituximab [ 18 ]. Detectable B cells (at least 40/mm 3 ) and a long time since the last exposure to rituximab have been associated with the development of anti-SARS-CoV-2 spike protein antibodies after the booster vaccine [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical and Serological Follow-Up of 216 Patients with Hematological Malignancies after Vaccination with Pfizer-BioNT162b2 mRNA COVID-19 in a Real-World Study

et al. 2023

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Hematological malignancies (HMs) have heterogeneous serological responses after vaccination due to disease or treatment. The aim of this real-world study was to analyze it after Pfizer-BioNT162b2 mRNA vaccination in 216 patients followed up for 1 year. The first 43 patients had an initial follow-up by a telemedicine (TM) system with no major events reported. The anti-spike IgG antibodies were checked 3–4 weeks post-first vaccination and every 3–4 months, by two standard bioassays and a rapid serological test (RST). Vaccine boosts were given when the level was <7 BAU/mL. Patients who did not seroconvert after 3–4 doses received tixagevimab/cilgavimab (TC). Fifteen results were discordant between two standard bioassays. Good agreement was observed between the standard and RST in 97 samples. After two doses, 68% were seroconverted (median = 59 BAU/mL) with a median of 162 BAU/mL and 9 BAU/mL, respectively, in untreated and treated patients (p < 0.001), particularly for patients receiving rituximab. Patients with gammaglobulin levels < 5 g/L had reduced seroconversion compared to higher levels (p = 0.019). The median levels were 228 BAU/mL post-second dose if seroconverted post-first and second, or if seroconverted only post-second dose. A total of 68% of post-second dose negative patients were post-third dose positive. A total of 16% received TC, six with non-severe symptomatic COVID-19 within 15–40 days. Personalized serological follow-up should apply particularly to patients with HMs.

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Serological Response to BNT162b2 Anti-SARS-CoV-2 Vaccination in Patients with Inflammatory Rheumatic Diseases: Results From the RHEUVAX Cohort

Cited by 12 publications

References 53 publications

Efficacy of COVID-19 mRNA vaccination in patients with autoimmune disorders: humoral and cellular immune response

Efficacy of COVID-19 mRNA vaccination in patients with autoimmune disorders: humoral and cellular immune response

Optimal time for COVID-19 vaccination in rituximab-treated dermatologic patients

Clinical and Serological Follow-Up of 216 Patients with Hematological Malignancies after Vaccination with Pfizer-BioNT162b2 mRNA COVID-19 in a Real-World Study

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