Diminished responses to mRNA-based SARS-CoV-2 vaccines in individuals with rheumatoid arthritis on immune- modifying therapies

Article Clinical Neurology

Longitudinal characterisation of B and T-cell immune responses after the booster dose of COVID-19 mRNA-vaccine in people with multiple sclerosis using different disease-modifying therapies

Alessandra Aiello et al.

Summary: COVID-19 vaccine booster strengthens humoral and Th1-cell responses and increases T-EM cells in patients with multiple sclerosis.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2023)

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Article Rheumatology

Factors associated with COVID-19 breakthrough infection among vaccinated patients with rheumatic diseases: A cohort study

Naomi J. Patel et al.

Summary: Rheumatic disease patients on multiple immunomodulators are at a higher risk of breakthrough infection, while recipients of mRNA-1273 vaccine have a lower risk compared to BNT162b2 recipients.

SEMINARS IN ARTHRITIS AND RHEUMATISM (2023)

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Article Biochemistry & Molecular Biology

SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron

Alison Tarke et al.

Summary: T cell responses induced by different vaccine platforms cross-recognize early SARS-CoV-2 variants, while memory B cells and neutralizing antibodies show significant decreases. The majority of memory T cell responses are preserved against variants, with lower recognition of Omicron by memory B cells.

CELL (2022)

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Article Clinical Neurology

Determinants of COVID-19-related lethality in multiple sclerosis: a meta-regression of observational studies

Luca Prosperini et al.

Summary: This study aimed to identify risk factors for increased lethality of COVID-19 in patients with multiple sclerosis (MS). The results showed that, in addition to age and comorbidities shared with the general population, there were MS-specific factors influencing the lethality of COVID-19, such as progressive disease course and current treatment with anti-CD20 agents. These findings suggest the need for a risk mitigation plan for patients with progressive MS and those treated with anti-CD20 agents.

JOURNAL OF NEUROLOGY (2022)

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Review Immunology

Response to Vaccines in Patients with Immune-Mediated Inflammatory Diseases: A Narrative Review

Beatriz Garcillan et al.

Summary: Patients with immune-mediated inflammatory diseases (IMIDs) receiving biologic therapies may experience attenuated vaccine responses. Certain therapies impair the immunogenicity and antibody responses to vaccines, while others do not affect immune responses. SARS-CoV-2 vaccination appears to be safe and well tolerated in IMID patients, but the efficacy may be reduced compared to healthy individuals.

VACCINES (2022)

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Article Rheumatology

Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases

Cristiana Sieiro Santos et al.

Summary: Patients with IMRD receiving immunosuppressive therapies exhibit impaired immunogenicity after receiving mRNA SARS-CoV-2 vaccines, with drugs like methotrexate and azathioprine showing varying levels of impact on vaccine responses. Abatacept and B-cell depleting therapies have deleterious effects, while anticytokines help preserve immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on vaccine immunogenicity warrant consideration, and humoral and cellular responses show weak correlation while CD4 and CD8 responses are tightly correlated, suggesting a more nuanced evaluation than seroconversion alone.

RMD OPEN (2022)

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Review Medicine, Research & Experimental

Application and pharmacological mechanism of methotrexate in rheumatoid arthritis

Zixuan Zhao et al.

Summary: The effectiveness of MTX in treating RA is due to multiple mechanisms of action, such as folate antagonism, promotion of adenosine accumulation, regulation of inflammatory signaling pathways, bone protection, and maintenance of immune system function.

BIOMEDICINE & PHARMACOTHERAPY (2022)

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Article Biochemistry & Molecular Biology

Imprinted SARS-CoV-2-specific memory lymphocytes define hybrid immunity

Lauren B. Rodda et al.

Summary: Research found that individuals previously infected with SARS-CoV-2 generate more specific memory B cells, variant-neutralizing antibodies, and a distinct population of memory CD4(+) T cells compared to those who were previously naive. Additional vaccination does not replicate the unique CD4(+) T cell cytokine profile observed in previously infected individuals.

CELL (2022)

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Article Immunology

Cutting Edge: Effect of Disease-Modifying Therapies on SARS-CoV-2 Vaccine-Induced Immune Responses in Multiple Sclerosis Patients

Yevgeniy Yuzefpolskiy et al.

Summary: This study found that MS patients treated with different modifying therapies have varied immune responses to SARS-CoV-2 vaccines. B cell depletion and fingolimod therapy significantly reduced S-specific antibody response, and fingolimod therapy also compromised CD4 and CD8 T cell responses.

JOURNAL OF IMMUNOLOGY (2022)

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Article Rheumatology

American College of Rheumatology Guidance for COVID-19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 4

Jeffrey R. Curtis et al.

Summary: This study aims to provide guidance for rheumatology providers on the use of COVID-19 vaccines in patients with rheumatic and musculoskeletal diseases. By summarizing the available literature and data, the study offers recommendations on vaccine efficacy, safety, and the use of immunomodulatory therapies during vaccination.

ARTHRITIS & RHEUMATOLOGY (2022)

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Article Immunology

Kinetics of the B- and T-Cell Immune Responses After 6 Months From SARS-CoV-2 mRNA Vaccination in Patients With Rheumatoid Arthritis

Chiara Farroni et al.

Summary: This study assessed the kinetics of humoral and cell-mediated responses in rheumatoid arthritis patients treated with different immunosuppressive therapies after receiving SARS-CoV-2 vaccination. The results showed a reduction in antibody titers after 6 months, although they were still detectable in a majority of patients. B-cell and T-cell responses were also weakened.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Rheumatology

Effectiveness of SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on DMARDs: as determined by antibody and T cell responses

Benazir Saleem et al.

Summary: This study assessed the antibody and T cell responses to SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on disease-modifying antirheumatic drugs (DMARDs). The results showed reduced vaccine responses in RA patients, especially with certain DMARDs. However, subsequent vaccinations improved the immune response in some patients.

RMD OPEN (2022)

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Article Immunology

IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2

Malika Hale et al.

Summary: Using monoclonal antibodies built from SARS-CoV-2-specific memory B cells, Hale et al. demonstrate that IgM antibodies outperform IgG in neutralization assays against mutated variants. The authors suggest that IgM antibodies may be useful therapeutically, and that IgM memory B cells may be underappreciated protectors against rapidly evolving pathogens.

JOURNAL OF EXPERIMENTAL MEDICINE (2022)

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Article Rheumatology

Antibody development after COVID-19 vaccination in patients with autoimmune diseases in the Netherlands: a substudy of data from two prospective cohort studies

Laura Boekel et al.

Summary: This study found that older patients with autoimmune diseases on specific immunosuppressive drugs may have delayed antibody development after the first COVID-19 vaccination. However, second or repeated exposure to SARS-CoV-2, either through infection or vaccination, can improve humoral immunity in these patients. Delaying the second dose of COVID-19 vaccines in patients receiving immunosuppressive drugs should be avoided, and future studies including younger patients are needed to confirm the generalizability of the results.

LANCET RHEUMATOLOGY (2021)

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Article Biochemistry & Molecular Biology

Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19

Lauren B. Rodda et al.

Summary: The study found that individuals recovered from mild COVID-19 develop sustained SARS-CoV-2-specific immunological memory for at least 3 months, including immunoglobulin antibodies, neutralizing plasma, and memory B and T cells. These memory lymphocytes exhibit potent antiviral function, aiding in immune defense.

CELL (2021)

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Letter Rheumatology

COVID-19 vaccination in immunocompromised patients

Bhavin Sonani et al.

CLINICAL RHEUMATOLOGY (2021)

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Article Multidisciplinary Sciences

Correlates of protection against SARS-CoV-2 in rhesus macaques

Katherine McMahan et al.

Summary: Adoptive transfer of purified IgG from convalescent macaques protects naive macaques against SARS-CoV-2 infection, and cellular immune responses contribute to protection against rechallenge with SARS-CoV-2. The findings suggest that relatively low antibody titres are sufficient for protection against SARS-CoV-2 in macaques, while higher antibody titres are required for treatment of SARS-CoV-2 infection.

NATURE (2021)

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Article Microbiology

Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies

Allison J. Greaney et al.

Summary: The evolution of SARS-CoV-2 may impact the recognition of the virus by human antibody-mediated immunity, with mutations affecting antibody binding varying significantly among individuals and within the same individual over time. Despite this variability, mutations that greatly reduce antibody binding usually occur at specific sites in the RBD, with E484 being the most crucial. These findings can inform surveillance efforts for SARS-CoV-2 evolution in the future.

CELL HOST & MICROBE (2021)

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Article Cell Biology

CERI, CEFX, and CPI: Largely Improved Positive Controls for Testing Antigen-Specific T Cell Function in PBMC Compared to CEF

Alexander A. Lehmann et al.

Summary: Monitoring antigen-specific T cell immunity requires functional tests that include positive controls for CD8+ T cells, CD4+ T cells, and APC compartments to assess the PBMC's functional fitness accurately.

CELLS (2021)

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Article Rheumatology

Efficacy of anti-SARS-CoV-2 mRNA vaccine in systemic autoimmune disorders: induction of high avidity and neutralising anti-RBD antibodies

Chiara Tani et al.

Summary: Double-dose vaccination in patients with SARDs induced anti-RBD IgG and IgA antibodies in amounts not significantly different from controls, characterized by high avidity and neutralizing activity.

RMD OPEN (2021)

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Review Rheumatology

Impact of disease-modifying antirheumatic drugs on vaccine immunogenicity in patients with inflammatory rheumatic and musculoskeletal diseases

Marcia A. Friedman et al.

Summary: Patients with rheumatic diseases are at increased risk of infectious complications, and disease-modifying antirheumatic drugs can reduce the immunogenicity of common vaccines. Different medications have varying impacts on vaccine immunogenicity, with rituximab having the most substantial effect and Janus kinase and tumour necrosis factor inhibitors decreasing antibody titres. Emerging data suggest that the effect of these medications on the SARS-CoV-2 vaccine immunogenicity is similar to other vaccines, but more research is needed.

ANNALS OF THE RHEUMATIC DISEASES (2021)

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Article Rheumatology

Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study

Victoria Furer et al.

Summary: Vaccination with mRNA BNT162b2 vaccine showed reduced immunogenicity in patients with AIIRD compared to the general population, with risk factors including older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. However, most patients maintained stable disease activity post-vaccination.

ANNALS OF THE RHEUMATIC DISEASES (2021)

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Article Rheumatology

Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease

Rebecca H. Haberman et al.

Summary: The study found that patients with immune-mediated inflammatory diseases (IMIDs) on methotrexate treatment showed impaired humoral and cellular immune response to COVID-19 mRNA vaccines, while healthy subjects and IMID patients on biologic treatments demonstrated strong antibody responses. These results suggest that different strategies may need to be explored to enhance immunization efficacy for IMID patients on methotrexate treatment.

ANNALS OF THE RHEUMATIC DISEASES (2021)

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Letter Medicine, General & Internal

Comparison of SARS-CoV-2 Antibody Response Following Vaccination With BNT162b2 and mRNA-1273

Deborah Steensels et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)

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Article Biochemistry & Molecular Biology

Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

Sokratis A. Apostolidis et al.

Summary: Patients with multiple sclerosis on anti-CD20 monotherapy exhibit significantly reduced SARS-CoV-2-specific antibodies and memory B cells, while CD4(+) and CD8(+) T cells are robustly activated compared to healthy controls after receiving BNT162b2 or mRNA-1273 mRNA vaccination.

NATURE MEDICINE (2021)

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Article Immunology

ImmunosuppressiveTherapies Differently Modulate Humoral- and T-Cell-Specific Responses to COVID-19 mRNA Vaccine in Rheumatoid Arthritis Patients

Andrea Picchianti-Diamanti et al.

Summary: In RA patients, the majority developed antibody-specific and whole-blood spike-specific T-cell responses following COVID-19 mRNA vaccine administration, with stable disease activity. The magnitude of these specific responses depended on the immunosuppressive therapy administered.

FRONTIERS IN IMMUNOLOGY (2021)

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Letter Medicine, General & Internal

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Danuta M. Skowronski et al.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Article Cell Biology

Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases

Alison Tarke et al.

Summary: By studying T cell responses in 99 convalescent COVID-19 cases, we identified various HLA-restricted epitopes derived from SARS-CoV-2 and observed distinct patterns of immunodominance. The epitopes were combined into megapools to facilitate the identification and quantification of virus-specific CD4(+) and CD8(+) T cells.

CELL REPORTS MEDICINE (2021)

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Article Virology