evere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people around the world 1 . Brazil is among those countries with the highest numbers of confirmed cases of, and deaths from, SARS-CoV-2 (refs. 1,2 ), with >430,000 deaths registered and approximately 15 million cases as of May 2021 (ref. 1 ). A second infection wave was driven by the Gamma coronavirus variant 3 , which is considered to be 2.5-fold more contagious than the original strain 4 and possibly associated with a higher risk for hospitalization and intensive care unit admission in patients younger than 60 years of age 5 . This second peak in March and April 2021 resulted in more than double the reported coronavirus disease 2019 (COVID-19) cases of the first peak in 2020 (ref. 6 ). Vaccines are therefore essential in regard to reducing COVID-19 mortality and morbidity.Although phase 3 clinical trials results are still being consolidated in China,

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Prognosis of several autoimmune diseases, especially rheumatoid arthritis (RA), ankylosing spondylitis, Crohn's disease (CD), and psoriasis, usually refractory to conventional treatment improved considerably with the introduction of tumor necrosis factor alpha (TNF-alpha) antagonistic agents, which is now available (infliximab, etanercept, and adalimumab). However, a portion of patients persists with active disease, infusion reactions, and relapses even during current biological therapy. One of the reasons for this is the associated immunogenicity to these drugs. The incentive for induction of antibodies against anti-TNF-alpha agent depends mainly on its constitution. Chimerical drugs have a higher capacity of inducing immunogenicity compared to completely human drugs. Among the three anti-TNF-alpha agents, this phenomenon has been studied mainly in patients using infliximab, especially in RA and CD. The prevalence of anti-infliximab antibodies in RA varies from 12% to 44% and seems to be inversely proportional to the level of seric infliximab and therapeutic response. The use of etanercept was associated to the development of anti-etanercept antibodies in 0% to 18% of patients, without apparent effect on effectiveness or adverse events. Studies with RA and CD patients show prevalence of anti-adalimumab antibodies from 1% to 87%. Immunosuppressive drug addiction can reduce the induction of anti-TNF-alpha antibodies.

Objective.To assess the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with juvenile autoimmune rheumatic disease (ARD) and healthy controls, because data are limited to the adult rheumatologic population.Methods.A total of 237 patients with juvenile ARD [juvenile systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), juvenile scleroderma, and vasculitis] and 91 healthy controls were vaccinated. Serology for anti-H1N1 was performed by hemagglutination inhibition assay. Seroprotection rate, seroconversion rate, and factor-increase in geometric mean titer (GMT) were calculated. Adverse events were evaluated.Results.Age was comparable in patients and controls (14.8 ± 3.0 vs 14.6 ± 3.7 years, respectively; p = 0.47). Three weeks after immunization, seroprotection rate (81.4% vs 95.6%; p = 0.0007), seroconversion rate (74.3 vs 95.6%; p < 0.0001), and the factor-increase in GMT (12.9 vs 20.3; p = 0.012) were significantly lower in patients with juvenile ARD versus controls. Subgroup analysis revealed reduced seroconversion rates in JSLE (p < 0.0001), JIA (p = 0.008), JDM (p = 0.025), and vasculitis (p = 0.017). Seroprotection (p < 0.0001) and GMT (p < 0.0001) were decreased only in JSLE. Glucocorticoid use and lymphopenia were associated with lower seroconversion rates (60.4 vs 82.9%; p = 0.0001; and 55.6 vs 77.2%; p = 0.012). Multivariate logistic regression including diseases, lymphopenia, glucocorticoid, and immunosuppressants demonstrated that only glucocorticoid use (p = 0.012) remained significant.Conclusion.This is the largest study to demonstrate a reduced but adequate immune response to H1N1 vaccine in patients with juvenile ARD. It identified current glucocorticoid use as the major factor for decreased antibody production. The short-term safety results support its routine recommendation for patients with juvenile ARD. ClinicalTrials.gov; NCT01151644.

The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644).

Objective Vitamin D has an important immunomodulatory effect, but there are no trials that directly address the boosting of serum levels of 25‐hydroxyvitamin D (25[OH]D) in juvenile‐onset systemic lupus erythematosus (SLE). The aim of this study was to evaluate the effect of vitamin D supplementation on disease activity and fatigue in juvenile‐onset SLE. Methods This study was a randomized, double‐blind, placebo‐controlled, 24‐week trial. Forty juvenile‐onset SLE patients were randomized (1:1) to receive oral cholecalciferol 50,000 IU/week (juvenile‐onset SLE‐VitD) or placebo (juvenile‐onset SLE‐PL). Medications remained stable throughout the study. Serum levels of 25(OH)D were measured using radioimmunoassay. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measurement (ECLAM). Fatigue was assessed using the Kids Fatigue Severity Scale (K‐FSS). Results At baseline, groups were similar regarding age, body mass index, organ involvement, glucocorticoid dose, use of immunosuppressive drugs, SLEDAI, ECLAM, K‐FSS, and levels of 25(OH)D. After 24 weeks, the mean level of 25(OH)D was higher in the juvenile‐onset SLE‐VitD group than in the juvenile‐onset SLE‐PL group (P < 0.001). At the end of the intervention, a significant improvement in SLEDAI (P = 0.010) and in ECLAM (P = 0.006) was observed in the juvenile‐onset SLE‐VitD group compared to the juvenile‐onset SLE‐PL group. Regarding fatigue evaluation, a reduction of fatigue related to social life score was found in the juvenile‐onset SLE‐VitD group compared to the juvenile‐onset SLE‐PL group (P = 0.008). Cholecalciferol was well tolerated with no serious adverse events. Conclusion This study suggests that cholecalciferol supplementation for 24 weeks is effective in decreasing disease activity and improving fatigue in juvenile‐onset SLE patients.

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Objective. Recent findings demonstrated a reduced immunogenicity of the influenza A H1N1/2009 vaccine in juvenile rheumatic diseases. However, a point of concern is whether the vaccine could induce disease flares. The aim of this study was to assess the disease safety of and the possible influence of disease parameters and therapy on nonadjuvant influenza A H1N1 vaccine response of juvenile systemic lupus erythematosus (SLE) patients. Methods. One hundred eighteen juvenile SLE patients and 102 healthy controls of a comparable age were vaccinated. Seroprotection rate, seroconversion rate, and factor increase in geometric mean titer (GMT) were calculated and effective immune response was defined by the Food and Drug Administration and the European Committee for Proprietary Medicinal Products vaccine immunologic standards. Disease parameters, treatment, and adverse events were evaluated. Results. Age was comparable in juvenile SLE patients and controls (mean ؎ SD 16.0 ؎ 3.5 versus 15.9 ؎ 4.5 years; P ‫؍‬ 0.26). Three weeks after immunization, seroprotection rate (73.7% versus 95.1%; P < 0.001), seroconversion rate (63.6% versus 91.2%; P < 0.001), GMT (90.8 versus 273.3; P < 0.001), and factor increase in GMT (8.1 versus 19.9; P < 0.001) were significantly lower in juvenile SLE patients versus controls. Nonseroconversion was associated with a higher frequency of patients with a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score >8 (48.8% versus 24%; P ‫؍‬ 0.008) and a higher mean ؎ SD current glucocorticoid dosage (18 ؎ 21.4 versus 10.5 ؎ 12.5 mg/day; P ‫؍‬ 0.018). Multivariate logistic regression including a SLEDAI-2K score >8 revealed that only the SLEDAI-2K remained a significant factor for nonseroconversion (odds ratio 0.42, 95% confidence interval 0.18 -0.98; P ‫؍‬ 0.045). Disease parameters remained stable throughout the study and no severe vaccine adverse events were observed. Conclusion. The present study demonstrated adequate disease safety and is the first to discriminate that high disease activity impairs influenza A H1N1/2009 vaccine antibody production in juvenile SLE, in spite of an overall immune response within recommended levels.