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Predicting COVID-19 vaccination response in populations who are immunosuppressed

2023; Elsevier BV; Volume: 5; Issue: 8 Linguagem: Inglês

10.1016/s2665-9913(23)00185-6

2665-9913

Katie Bechman, Mark Russell, James Galloway,

COVID-19 and healthcare impacts

Although the risk posed by the COVID-19 pandemic has subsided for many people, it continues to be a serious concern for people who are immunocompromised. Vaccination is a key strategy in mitigating the risk of infection, particularly for patients with autoimmune diseases, patients with haematological malignancies, and recipients of organ transplants. The pandemic has provided a unique opportunity for the health-care research community to study vaccination in more detail than ever before, and on an unprecedented scale. The lessons we learn from the COVID-19 pandemic will strengthen our understanding of how to protect against other infections. In The Lancet Rheumatology, Fiona Pearce and colleagues1Pearce FA Lim SH Bythell M et al.Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODY.Lancet Rheumtol. 2023; 5: 474-482Google Scholar present cross-sectional data from the MELODY study, a prospective observational cohort designed to assess COVID-19 vaccination responses in patients who are immunosuppressed in the UK. The population under study included recipients of solid organ transplants, patients with rare autoimmune rheumatic diseases (predominantly systemic lupus erythematosus and small vessel vasculitis), and individuals with lymphoid malignancies. Study participants had received three or more COVID-19 vaccinations, providing valuable information on cumulative vaccine response. The Article presents baseline data and explores characteristics that could explain variation in individual response to COVID-19 vaccines. The authors also present a linked subanalysis that assessed associations between mental health comorbidities and vaccine responses in these cohorts. A strength of this study is its methodological approach to collating data. National disease registers with linked hospital data were used to identify and invite over 100 000 individuals across the disease areas of interest. 28 411 (27·9%) participants completed an online questionnaire and were enrolled into the study. These data represent an enormous sample size, for whom the authors were able to identify key predictors of vaccine response. The next methodological feat was to ask participants to return the results of a SARS-CoV-2 antibody test, done in their own home using a commercially available assay. These serological data were available for 23 411 patients, representing 81·1% of participating individuals. The number of vaccinations and previous SARS-CoV-2 infection were associated with a greater likelihood of a positive antibody response, whereas older age (for each 10-year increase) and immunosuppressive medications were associated with a negative antibody response. The finding that immunosuppressive medications were associated with reduced antibody response was highlighted in the solid organ transplant cohort, with recipients of lung transplants having the lowest likelihood of seropositivity (odds ratio [OR] 0·59 [95% CI 0·46–0·77]), whereas recipients of liver transplants had the greatest likelihood of seropositivity (1·27 [1·09–1·49]), when compared with recipients of a kidney transplant. This finding probably reflects the relative strength of immunosuppressive regimens accompanying these transplants. For rare autoimmune rheumatic diseases, the pattern was similar. Patients with small vessel vasculitis had the lowest likelihood of an antibody response (OR 0·69 [0·55–0·87]), aligning with the disease indication for which more aggressive immunosuppressive regimens are typically prescribed. As seen in previous studies,2Spiera R Jinich S Jannat-Khah D Rituximab, but not other antirheumatic therapies, is associated with impaired serological response to SARS- CoV-2 vaccination in patients with rheumatic diseases.Ann Rheum Dis. 2021; 80: 1357-1359Crossref PubMed Scopus (144) Google Scholar, 3Moor MB Suter-Riniker F Horn MP et al.Humoral and cellular responses to mRNA vaccines against SARS-CoV-2 in patients with a history of CD20 B-cell-depleting therapy (RituxiVac): an investigator-initiated, single-centre, open-label study.Lancet Rheumatol. 2021; 3: e789-e797Summary Full Text Full Text PDF PubMed Scopus (153) Google Scholar there was a clear and consistent association between anti-CD20 therapy (eg, rituximab) and reduced seropositivity in the rare autoimmune rheumatic disease cohort (OR 0·07 [0·05–0·10]). What is particularly informative about this study is the finding that IgG anti-spike antibodies were undetectable in 2310 (23·3%) recipients of solid organ transplants, 922 (14·1%) patients with rare autoimmune rheumatic diseases, and 1366 (20·7%) patients with lymphoid malignancies despite all cohorts receiving three or more COVID-19 vaccinations. In the rare autoimmune rheumatic disease cohort, antibody response rates were even lower in some groups: 370 (27·1%) of 1364 patients with small vessel vasculitis had no detectable antibody response, whereas 404 (49·9%) of 810 individuals who had received anti-CD20 therapy in the previous year had no detectable antibody response. This information helps to refine our understanding of which patients are least likely to mount antibody responses and will undoubtedly help to target vaccination efforts. The study is not without limitations. We need to be mindful about sampling bias, particularly for rare and heterogeneous rheumatic conditions. Reaching patients with diseases such as systemic sclerosis or myositis is challenging, and to have recruited and collected data from over 1300 individuals with these diagnoses is impressive. However, there is substantial variation in the severity and clinical manifestations of these diagnoses, which needs to be taken into consideration when interpreting the findings. We also need to acknowledge that the study findings are derived from humoral measures of immunity, and there will undoubtedly be differences between antibody and T-cell-mediated immunological responses within the study cohorts. It is also difficult to draw firm conclusions from the analyses of mental health comorbidities and antibody response. In recipients of solid organ transplants, the authors reported an association between a higher burden of psychological distress and reduced odds of an antibody response. Although interesting, these findings might partly be explained by unmeasured confounding linked to disease severity, which was not robustly measured in the study. This study has substantial clinical implications. Most notably, we must continue to advocate for vaccination against COVID-19 in patients, especially patients who are older or receiving more aggressive immunosuppression regimens (particularly rituximab). Just as important are the research questions that this study has generated: how often should we be assessing the serological response to COVID-19 vaccinations? Should we be assessing the response to other vaccinations (eg, pneumococcus) in individuals who are at risk? Furthermore, how can we harness population-level data such as these to provide timely answers to important clinical questions in the future? KB reports institutional funding from Pfizer; personal fees from Galapagos and Menarini; and support for attending meetings or travel from UCB. MDR reports personal fees from Lilly, Galapagos, and Menarini; support for attending meetings or travel from Lilly, Pfizer, Janssen, and UCB; and advisory board fees from Biogen. JG reports personal fees from Abbvie, Biovitrum, Bristol Myers Squib, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, and UCB. Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODYApproximately one in five recipients of solid organ transplants, individuals with rare autoimmune rheumatic diseases, and individuals with lymphoid malignancies have no detectable IgG anti-spike antibodies despite three or more vaccine doses, but this proportion decreases with sequential booster doses. Choice of immunosuppressant and disease type is strongly associated with serological response. Antibody testing using lateral flow immunoassay tests could enable rapid identification of individuals who are most likely to benefit from additional COVID-19 interventions. Full-Text PDF Open Access