Infections
ORIGINAL RESEARCH Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases
Cristiana Sieiro Santos, 1 Sara Calleja Antolin, 2 Clara Moriano Morales, 1 Juan Garcia Herrero, 2 Elvira Diez Alvarez, 1 Fernando Ramos Ortega, 3 Jose G Ruiz de Morales 2
To cite: Sieiro Santos C, Calleja Antolin S, Moriano Morales C, et al . Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune- mediated inflammatory rheumatic diseases. RMD Open 2022; 8 :e001898. doi:10.1136/ rmdopen-2021-001898 ► Additional supplemental material is published online only. To view, please visit the journal online (http://dx.doi.org/1 0. 1136/rmdopen-2021-0 01898).
ABSTRACT Background Patients with immune-mediated rheumatic diseases (IMRDs) are commonly treated with immunosuppressors and prone to infections. Recently introduced mRNA SARS-CoV-2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-CoV-2 mRNA vaccines. Aims To fully characterise B-cell and T-cell immune responses elicited by mRNA SARS-CoV-2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine’s immunogenicity. Methods Humoral, CD4 and CD8 immune responses were investigated in 100 naïve patients with SARS- CoV-2 with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS- CoV-2 mRNA vaccine. Responses were compared with age, gender and disease-matched patients with IMRD not receiving immunosuppressors and with healthy controls. Results Patients with IMRD showed decreased seroconversion rates (80% vs 100%, p=0.03) and cellular immune responses (75% vs 100%, p=0.02). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept decreased humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed impaired humoral responses, but cellular responses were often preserved. Antibody titres were reduced with mycophenolate and azathioprine but preserved with leflunomide and anticytokines. Conclusions Patients with IMRD exhibit impaired SARS-CoV-2 vaccine immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine’s immunogenicity.
INTRODUCTION Patients with immune-mediated rheumatic diseases (IMRDs) are considered at-risk for serious infections as a result of the underlying dysregulation of their immune system and the common use of targeted immune-modulating therapies and immunosuppressors. 1 On the scenario of the global SARS-CoV-2 pandemic, recent data indicate that patients with rheu- matic diseases with low/moderate disease activity on monotherapy, but steroids, are not at a higher risk of severe manifestations of COVID-19. 2 3 In fact, the use of downstream anti-inflammatory immunomodulating thera- pies such as anti-TNF, JAK inhibitors, anti-IL-1 and IL-6 inhibitors can have a beneficial effect on the management of pathological immune ► A weak correlation between elicited humoral and cellular responses, but strong correlation between CD4 and CD8 T-cell responses, were observed. How might this impact on clinical practice or further developments? ► In immunosuppressed patients with IMRD, measure- ment of cellular immune responses might be nec- essary to fully evaluate vaccinesvaccine’s efficacy. Key messages What is already known about this subject? ► Immunogenicity to common vaccines is compro- mised in IMRD under immunosuppressors. ► SARS-CoV-2 mRNA vaccines are highly effective in healthy people. What does this study add? In patients with IMRD vaccinated with SARS-CoV-2 mRNA vaccines: ► Immunogenicity was reduced at different degrees and at different points of the immune response de- pending on the therapies used.
Received 25 August 2021 Accepted 5 December 2021
1 Rheumatology, Complejo Asistencial Universitario de Leon, Leon, Spain 2 Immunology, Complejo Asistencial Universitario de Leon, Leon, Spain 3 Hematology, Complejo Asistencial Universitario de Leon, Leon, Spain Correspondence to Dr Jose G Ruiz de Morales; jgarcir@gmail.c om © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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Sieiro Santos C, et al . RMD Open 2022; 8 :e001898. doi:10.1136/rmdopen-2021-001898
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