Very low rate of humoral response after a third COVID-19 vaccine dose in patients with autoimmune diseases treated with rituximab and non-responders to two doses

Bitoun, Samuel; Avouac, Jérôme; Henry, J.; Ghossan, R.; Tabaa, Omar Al; Belkhir, Rakiba; Nocturne, Gaëtane; Mariaggi, Alice Andrée; Rozenberg, Flore; Vauloup‐Fellous, Christelle; Mariette, Xavier; Séror, Raphaèle

doi:10.1136/rmdopen-2022-002308

Cited by 14 publications

(19 citation statements)

References 7 publications

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“…In the largest study to date, only 14.5% (9/62) of patients seroconverted following a third dose. The authors did not measure B-cell status and, therefore, do not have data on the relevance of B-cell reconstitution to likelihood of a serologic response (16). Similarly, another study found that only 27% (15/55) of RTX-treated patients developed antibodies following the booster.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, there is a paucity of data regarding factors associated with successful seroconversion following a booster dose in RTX-treated patients. In the observational studies specifically on RTX-treated AIRD patients reported to date, anywhere from 0% to 47% of patients that were previously seronegative were able to develop antibodies after the booster (10)(11)(12)(13)(14)(15)(16)(17)(18). The study that achieved a seroconversion rate of 47% was included only capturing 15 patients (11).…”

Section: Introductionmentioning

confidence: 99%

“…In three of these studies, a positive association was found between exhibiting a positive CD19% and vaccine response (11)(12)(13). The other studies either did not assess B-cell reconstitution or were limited by small numbers (<10) of patients who seroconverted (10,(14)(15)(16)(17)(18). To better understand the relationship between the third dose of the mRNA COVID-19 vaccine with seroconversion among patients treated with RTX, we retrospectively assessed factors associated with COVID-19 vaccine response in 31 RTX-treated AIRD patients who had not demonstrated a serologic response to their initial COVID-19 vaccine series.…”

Section: Introductionmentioning

confidence: 99%

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B Cell Reconstitution is Associated With COVID-19 Booster Vaccine Responsiveness in Patients Previously Seronegative Treated With Rituximab

2022

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ObjectiveTo assess factors associated with serologic response to the COVID-19 booster vaccine in rituximab-treated autoimmune rheumatic disease patients previously serologically unresponsive to the initial vaccine series.MethodsA retrospective chart review of rituximab-treated patients who failed to demonstrate a serologic response to the first SARS-CoV-2 vaccination series and subsequently received an mRNA vaccine booster was performed. Serologic response four weeks or more after the booster was the primary outcome. T-tests, Fisher's exact tests, and Wilcoxon rank sum tests were used for comparisons.ResultsIn 31 previously seronegative patients, 68% seroconverted following a booster of the COVID-19 vaccine. B-cell reconstitution was significantly different between those with positive (median, IQR 1.785 (0.65, 3)) and negative (median, IQR 0 (0,0)) serologic responses to the booster. Days from last rituximab dosage was also statistically different among seroconverters (median, IQR 301 (251, 368)) versus non-seroconverters (median, IQR 188 (169, 245)). Demographic characteristics were not associated with serologic positivity. Positive predictive value of B-cell presence was 90.9% (95% CI: 70.8%, 98.9%) and negative predictive value was 100% (95% CI: 59%, 100%) for serologic response to the mRNA booster. Positive predictive value of time >6 months from last rituximab to the booster was 78.3% (95% CI 56.3%, 92.5%) and the negative predictive value was 62.5% (95% CI 24.5%, 91.5%).ConclusionDetectable B-cells and longer time from last rituximab exposure were associated with the development of anti-SARS-CoV-2 spike protein antibodies following the booster vaccine. These findings should be considered in timing boosters in rituximab-treated patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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B Cell Reconstitution is Associated With COVID-19 Booster Vaccine Responsiveness in Patients Previously Seronegative Treated With Rituximab

2022

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“…Cellular immune responses were not attenuated in patients receiving methotrexate or targeted biologics compared to healthy controls [ 136 ]. Another study reported a very low (14.5%) rate of humoral response after the third COVID-19 vaccine dose in patients with autoimmune diseases treated with rituximab who were non-responders to two doses [ 137 ].…”

Section: Immune Response To Sars-cov-2 Vaccinationmentioning

confidence: 99%

Immunity after COVID-19 Recovery and Vaccination: Similarities and Differences

et al. 2022

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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with a robust immune response. The development of systemic inflammation leads to a hyperinflammatory state due to cytokine release syndrome during severe COVID-19. The emergence of many new SARS-CoV-2 variants across the world deteriorates the protective antiviral immunity induced after infection or vaccination. The innate immune response to SARS-CoV-2 is crucial for determining the fate of COVID-19 symptomatology. T cell-mediated immunity is the main factor of the antiviral immune response; moreover, SARS-CoV-2 infection initiates a rapid B-cell response. In this paper, we present the current state of knowledge on immunity after COVID-19 infection and vaccination. We discuss the mechanisms of immune response to various types of vaccines (nucleoside-modified, adenovirus-vectored, inactivated virus vaccines and recombinant protein adjuvanted formulations). This includes specific aspects of vaccination in selected patient populations with altered immune activity (the elderly, children, pregnant women, solid organ transplant recipients, patients with systemic rheumatic diseases or malignancies). We also present diagnostic and research tools available to study the anti-SARS-CoV-2 cellular and humoral immune responses.

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“… 1 Moreover, RTX treatment and low B cell counts are associated with inadequate antibody responses, even after a third vaccination. 2 T cell responses seem largely intact, 3 but the impact on clinical protection remains unclear. Given the current predominance of SARS-CoV-2 Omicron sublineages, a reduced neutralisation capacity of antibodies must also be considered.…”

mentioning

confidence: 99%

Mild COVID-19 despite inadequate antibody response after repeated vaccinations in rheumatic disease patients with rituximab-induced B cell depletion: a case series

Hagen

Habermann²,

Hermann³

et al. 2022

RMD Open

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Very low rate of humoral response after a third COVID-19 vaccine dose in patients with autoimmune diseases treated with rituximab and non-responders to two doses

Cited by 14 publications

References 7 publications

B Cell Reconstitution is Associated With COVID-19 Booster Vaccine Responsiveness in Patients Previously Seronegative Treated With Rituximab

B Cell Reconstitution is Associated With COVID-19 Booster Vaccine Responsiveness in Patients Previously Seronegative Treated With Rituximab

Immunity after COVID-19 Recovery and Vaccination: Similarities and Differences

Mild COVID-19 despite inadequate antibody response after repeated vaccinations in rheumatic disease patients with rituximab-induced B cell depletion: a case series

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