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Background/Aims Patients with immune-mediated rheumatic diseases (IMRD) are commonly treated with immunosuppressors and are prone to infections. Recently introduced mRNA SARS-Cov2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-We aim to fully characterize B and T cell immune responses elicited by mRNA SARS-Cov2 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 147 SARS-Cov2-naive patients with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-Cov2 mRNA vaccine. Responses were compared with age, gender, and diseasematched IMRD patients not receiving immunosuppressors and with healthy controls Results IMRD patients showed decreased seroconversion rates (63% vs 100%, p=0.04) and cellular immune responses (59% vs 100%, p=0.007). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept deeply affected humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed severely impaired humoral responses but cellular responses were often preserved. Antibody titers were reduced with mycophenolate and azathioprine but preserved with leflunomide. Conclusion IMRD patients exhibit impaired SARS-CoV-2 vaccine-immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show the most 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.
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Objectives: To estimate COVID-19 infection rate in patients treated with bDMARDS due to rheumatic inflammatory diseases, determine the influence of the treatment as a risk or protective factor and studying the prognosis of rheumatic patients receiving biologic agents compared to general population in a third level Hospital setting in León, Spain. Methods: We performed an observational study including patients who received bD MARDs due to rheumatic diseases between December 1st 2019 and December 1st 2020 and examined the COVID-19 infection rate. We performed a multivariate logistic regression model to assess risk factors of COVID-19 infection Results: There was a total of 3711 patients with COVID-19 requiring hospitalization. 40 patients out of a total of 820 patients with rheumatic diseases (4.8%) receiving bD MARDs were infected witth COVID-19 and four required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 2.75%, and it was 0.48% among the group with underlying rheumatic diseases. Out of the 3711 patients, 423 patients died, 2 of which received treatment with biologic agents. Patients with rheumatic diseases who tested positive for COVID-19 were older (female: median age 60.8 IQR 46-74;male: median age 61.9 IQR 52-70.3) than those who were negative for COVID-19 (female: median age 58.3 IQR 48-69;male: median age 56.2 IQR 47-66), more likely to have hypertension (45% vs 26%, OR 2.25 (95%CI 1.14-4.27), p = 0.02), cardiovascular disease (23 % vs 9%, OR 2.85 (95%CI 1.31-6.23), p = 0.01), be smokers (13% vs 4.6%, OR 2.95 (95%CI 1.09-7.98), p = 0.04), receiving treatment with rituximab (20%vs 8%, 2.28 (CI 1.24-6.32), p = 0.02) and a higher dosage of glucocorticoids (OR 2.2 (1.2-10.23), p 0.02) and were less likely to be receiving treatment with IL-6 inhibitors (0.03% vs 14%, OR 0.16, (95%CI 0.10-0.97), p = 0.03). Patients who tested negative for COVID-19 were more likely to be treated with bDMARDs for a longer period (in months) than patients with a positive result (OR 0.54 (95%CI 0.22-0.87), p = 0.04).We found no differences in sex or rheumatological disease between patients who tested positive for COVID-19 and patients who tested negative. Conclusion: Overall, the use of bD MARDs was not associated with severe manifestations of COVID-19. Patients with rheumatic disease diagnosed with COVID-19 were more likely to be receiving a higher dose of glucocorticoids and treatment with rituximab. IL-6 inhibitors may have a protective effect.