RMD Open
responses, including cytokine storm developed in the context of severe COVID-19. 4–6 On the contrary, B-cell and T-cell depleting therapies in selected populations of patients have been associated with severe or prolonged SARS-CoV-2 infections. 7 8 The COVID-19 pandemic should be overcome by the recent introduction of the new genetic SARS-CoV-2 vaccines. Because of its reported unprecedented high effectiveness and safety, these vaccines—mRNA and adenoviral vector vaccines—are a major scientific break- through that will probably change current vaccine practices in a near future. Because they supply to recip- ient’s own cells the information to produce exogenous proteins, unmodified native antigen presentation by HLA I and II molecules to the immune system follows physiological routes. 9 Perhaps this feature underlays its high effectiveness across all ages. But the exact correlate of the elicited immune responses that confers protection against infection is not yet fully known. 10 Immunosuppressed patients were excluded from phase III trials of the mRNA vaccines currently approved by the EMA and FDA. 11 12 The management of IMRD typically requires immunosuppressive medications and biological agents to achieve and maintain disease remis- sion. Because of its novelty, scant information is nowa- days available on mRNA vaccine responses in patients with IMRD. However, it is well-known that older age, high dose steroids, high inflammatory activity index and immunosuppressive therapies are associated with decreased responses to conventional vaccines. 13 Here, we report exhaustive B, T CD4 and CD8 immunogenicity data after completing mRNA SARS-CoV-2 vaccination in 110 immunocompromised patients with IMRD under active immunosuppression and compare them to 50 immunocompetent patients with the same diagnosis and with 50 healthy controls.
lupus erythematosus (SLE), systemic sclerosis (SS) and Sjogren’s disease (SJ). Patients were classified into two groups: 110 actively receiving immunosuppressive ther- apies (cohort 1, IMRD ISP+), and 50 disease, age and gender-matched patients with IMRD without active immunosuppression for the last 2 years (cohort 2, IMRD ISP−). Both IMRD cohorts were compared with another cohort of 50 healthy vaccinated controls from healthcare personnel (cohort 3). On the basis of composite objective factors (online supplemental material 1), cohort 1 (IMRD ISP+) was defined as patients actively receiving one or more conven- tional synthetic disease modifying antirheumatic drugs (ie, methotrexate (MTX), leflunomide (LFM), azathio- prine (AZA), mycophenolate (MFM)) and/or biological disease modifying antirheumatic drugs (bDMARDs) such as CTLA4-Ig (abatacept), BLyS inhibitor (belimumab (BMB)) and anti-CD20 antibody (rituximab (RTX)). Cohort 2 (IMRD ISP−) was defined as patients with the same IMRD receiving non-steroidal anti-inflammatory drugs, antimalarials and/or bDMARDs blocking effector inflammatory cytokines such as anti-TNF (adalimumab, certolizumab, etanercept, golimumab, infliximab), IL-6 inhibitors (sarilumab and tocilizumab) and IL-1 inhibi- tors (anakinra). General exclusion criteria were previous serologically or PCR confirmed COVID-19, vaccination with any other SARS-CoV-2 vaccine, and in the control cohorts, a history or immunosuppressive treatment during the previous 2 years. The following variables were recorded: (1) age, (2) gender, (3) type of rheumatic disease, (4) brand of vaccine administered, (5) time since diagnosis, (6) accu- mulated treatments during the previous 2 years, (7) cumulative dose of glucocorticoids and MTX during the previous 2 years and (8) in RTX-treated patients, time since last infusion. Vaccination procedure All patients received a two-dose regimen of an mRNA vaccine (either mRNA-1273 or BNT162b2, online supple- mental material 2). Patients were first assessed at the rheumatology office within 2 weeks prior to vaccination and blood samples collected after at least 3 weeks (mean 37 days) of complete vaccination at the immunology laboratory. Assessment of humoral responses Humoral vaccine response was evaluated by means of SARS-CoV-2 Trimeric S IgG assay (Dia-Sorin). A value above 33.8 binding antibody units (BAU/mL) was considered positive, according to the manufacturer’s instructions. Assessment of cellular CD4 and CD8 responses Cellular CD4 and CD8 responses were analysed in vitro in freshly isolated peripheral blood lymphocytes (PBL) after stimulation with a peptide pool spanning the entire
METHODS Design
Longitudinal observational study conducted at Complejo Asistencial Universitario of León (Spain) between April and July 2021 to characterise the immune response to mRNA SARS-CoV-2 vaccines in patients with IMRD and determine the influence of immunosuppressive and biological therapies in the elicited immune response. The study was conducted according to the principles of the Declaration of Helsinki and approved by hospital’s institutional ethics committee. Study population We performed a consecutive sampling on the available IMRD population >18 years from CAULE’s rheumatology outpatient clinic. One hundred and sixty patients with IMRD with low/moderate disease activity index and twice vaccinated with an mRNA SARS-CoV-2 vaccine were selected according to disease and treatment. Selected diseases included rheumatoid arthritis (RA), systemic
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Sieiro Santos C, et al . RMD Open 2022; 8 :e001898. doi:10.1136/rmdopen-2021-001898
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