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Background:The efficacy of the COVID-19 vaccine in patients with autoimmune diseases (AID) depends on the underlying disease, the type of immunosuppression and the vaccine regimens administered. However, there are few studies evaluating immunogenicity according to immunosuppressive drugs and different COVID-19 vaccine platforms in a large cohort of patients with AID.Objectives:We aimed to determine the factors associated for vaccine response through anti-spike IgG antibodies 28 days after the third dose against COVID-19 in patients with AID.Methods:These data are from SAFER study: “Safety and efficacy on Covid-19 Vaccine in Rheumatic Disease”, a multicentric prospective phase IV study, in real life, in Brazil, started on May 2021. Data from this analysis were from 8 centers, from all Brazilian areas, after 2 or 3 doses of vaccine against COVID-19 in patients with AID age ≥ 18 years. Exclusion criteria were pregnancy, previous severe adverse events (AE) to any vaccine or other immunosuppression causes. Demographics, diagnoses and therapeutic regimens were collected. Available vaccines were adenoviral vectored vaccine (ChAdOx1, Astrazeneca), mRNA vaccine (BNT162b2, Pfizer–BioNTech) or inactivated SARS-COV-2 vaccine (Coronavac). Participants were followed up by means of blood collection for measurement of IgG antibody against SARS-CoV-2 spike receptor-binding domain by chemiluminescence (SARS-CoV-2-IgG-II Quant assay) at baseline and 28 days after the first, 2nd and 3rd doses. The seropositivity was defined for titers IgG-Spike ≥7.1 BAU/mL. The inferential statistical analysis included a comparison of the IgG value at the 4 time points were performed with the Wilcoxon/Mann-Whitney test. Simple and multiple regressions were carried out to determine which clinical and sociodemographic variables influenced the IgG value 28 days after the booster dose (T4). An alpha level of 5% significance was used in all analyses.Results:A total of 1101 participants were included and followed from the first dose. Of these, 785 participants received the 3-dose regimen and had samples taken during the four study times. Finally, only the most frequent vaccination schedules were filtered out, removing 68 participants. Thus, the final database has 704 participants with Systemic Lupus Erythematosus (SLE) N=249 (35%), Rheumatoid Arthritis (RA) N=134 (19%), Spondyloarthritis (SpA) N=99 (14%), Connective Tissue Disease (CTD) N=72 (10%), Sjögren’s Syndrome (SS) N=53 (7. 5%), Inflammatory bowel disease N=51 (7.2%) and Vasculitis N=46 (6.5%). Mean age was 41.3 (±12.2), female N=562, (78.0%). Vaccination regimens administered were: Coronavac + Coronavac + Pfizer N=226 (32.10%), AstraZeneca + AstraZeneca + Pfizer N=223 (31.68%), AstraZeneca + AstraZeneca + AstraZeneca N=139 (19.74%), Coronavac + Coronavac + AstraZeneca N=77 (10.94%), Pfizer + Pfizer + Pfizer N=32 (4.55%) and Coronavac + Coronavac + Coronavac N=7 (0.99%). The median titers of IgG antibodies against SARS-COV-2 increased progressively over the times, at baseline was 1.05 BAU/mL (0.2-26.8), at T2 (28 days after first dose) was 78.4 BAU/mL (11.9-437.2), at T3 (28 days after second dose) was 214.8 BAU/mL (74.2-683.0) and T4 (28 days after the third dose) was 1281.1 BAU/mL (376.7-3420.9). No serious adverse events were observed during the follow-up. The multivariate linear regression showed that greater titers of IgG antibodies were associated with pre-exposure to COVID (p<0.001), Pfizer booster regimens (p=0.008,0.002, 0.001 respectively), patients receiving non-immunosuppressant DMARDs or not using immunosuppressive medications (p<0.05). Rituximab was an independent factor for low titers (p<0.05) (Table 1 and Figure 1).Conclusion:All vaccines administered as third dose induced an increase in IgG-S titers antibodies. COVID pre-exposure, Pfizer booster regimens and patients receiving non-immunosuppressant DMARDs or without medications were independent predictors of higher humoral immune responses which is relevant in this immunosuppressed population.REFERENCES:NIL.Acknowledgements:Support from the Brazilian Society of Rheumatology (SBR). Funding by the Department of Science and Technology of the Ministry of Health, Brazil (DECIT).Disclosure of Interests:None declared.

Background:Breakthrough COVID-19 infections occurring in fully vaccinated people have been described. There is particular concern about the effectiveness of vaccination in patients with immune-mediated rheumatic diseases (IMRD). Data on the characteristics and prognosis of breakthrough COVID-19 among IMRD patients are scarce.Objectives:To describe demographic and clinical characteristics, COVID-19 presentation, and risk factors associated with hospitalization in this population.Methods:SAFER study is a Brazilian multicentric cohort evaluating safety and effectiveness of SARS-Cov-2 vaccines in patients with autoimmune diseases, ongoing since April, 2021. In this study, 1,128 fully vaccinated adult IMRD patients were analyzed. It describes the fully vaccinated IMRD patients presenting breakthrough COVID-19 (occurring ≥14 days after the second dose in a two-dose series or ≥14 days after a single-dose vaccine), from April, 2021 to February, 2023. Descriptive analysis, and a regression model to evaluate the variables associated with hospitalization due to COVID-19, were performed. The significant p-value was < 0.05.Results:160 fully vaccinated IMRD patients surviving breakthrough COVID-19 were included.Patients received 2 (19%), 3 (70%) or 4 (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n=150), with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (Oxford/AstraZeneca) (29%), and the second booster (n=112) with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (40%) or ChAdOx1 (Oxford/AstraZeneca) (26%). The characteristics of the population are shown in Table 1. Most (96%) patients reported COVID-19 symptoms, mainly headache (57%), cough (54%), rhinorrhea (51%), sore throat (49%), fever (46%), fatigue (32%), hyposmia (20%), dysgeusia (18%), and dyspnea (18%). Binary logistic regression for hospitalization due to breakthrough COVID-19 is in Table 2.Conclusion:Booster vaccine doses decreases, while higher disease activity or chronic use of corticosteroids increases the risk of hospitalization due to breakthrough COVID-19 infection in IMRD vaccinated patients. Fever or dyspnea in COVID-19 infection predict hospitalization in this population. New studies to evaluate the impact of breakthrough COVID-19 and the effects of vaccine booster doses in these patients are warranted.Table 1.Clinical demographic characteristics of the populationVariableBreakthrough COVID-19 (n=160)Age (years) (Mean (SD)44.1 (12.8)Female gender n(%)133 (83)White color n(%)63 (39)CTD/vasculitis n(%)98 (61)Inflammatory arthropathies n(%)62 (39)Rheumatic disease time length (Years)[Median (p25-p75)]9.5 (4-15)Rheumatic disease moderate/high activity n(%)23 (14%)Any comorbidity n(%)102 (63.8)Rheumatic disease treatmentCorticosteroid [n(%)]29 (18.1)bDMARD n(%)3 (1.9)TNFi n(%)38 (23.8)Rituximab n(%)13 (8.1)Immunosuppressant n(%)35 (21.8)csDMARD n(%)81 (50.6)tDMARD (JAKi) n(%)3 (1.8)CTD: connective tissue disease. b-DMARD: biologic disease modifying antirrheumatic drug (non-TNFi, non-rituximab). csDMARD: conventional synthetic DMARD. tDMARD: targeted DMARD.Table 2.Binary logistic regression for hospitalizationInitial modelFinal modelVariableExp(B) (95%CI)p-valueExp(B) (95%CI)p-valueDemographic and clinical characteristicsRheumatic disease moderate/high activity4.63 (1.71-12.5)0.0035.82 (1.89-17.94)0.002Number of COVID-19 vaccines0.44 (0.2-0,95)0.040.38 (0.16-0.94)0.04Treatment with corticosteroids2.4 (0.98-5.9)0.062.94 (1.03-8.37)0.04Lack of treatment with antirrheumatic drugs0.46 (0.16-1.28)0.14--COVID-19 SymptomsDysgeusia2.59 (1.06-6.32)0.04--Dyspnea4.3 (1.72-10.73)0.0023.58 (1.14-11.24)0.03Sore throat2,1 (0.9-4.89)0.008--Fever2.45 (0.89-5.49)0.043.04 (1.06-8.68)0.04Hyposmia2.2 (0.89-5.49)0.09--Cough2.42 (0.99-5.89)0.05--REFERENCES:NIL.Acknowledgements:We thank SAFER Study Group and the Brazilian Society of Rheumatology for supporting this study. This study was financed by the Brazilian Department of Science and Technology (TED 20/2021).Disclosure of Interests:None declared.

Background:Phase III clinical trials have shown that COVID-19 vaccines are safe and effective in healthy children. There are few studies in children with juvenile autoimmune disease (AID).Objectives:The study aims to evaluate the immunogenicity and safety of the vaccine against COVID-19 in Juvenile JAID in the real life.Methods:These data are from “Safety and efficacy on COVID-19 Vaccine in Rheumatic Disease” - SAFER study, a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine AID. Immunogenicity and adverse events (AE) were assessed, after 3 doses, in children compared to adults with AID. Inclusion criteria were fulfilling criteria according to international classification for AID. Exclusion criteria: pregnancy, previous severe AE to any vaccine and other immunosuppression causes. Stratification of post-vaccination AE was performed using a diary, filled out daily and returned at the end of 28 days of each dose. The IgG antibodies to SARS-CoV-2 spike receptor-binding domain by chemiluminescence were measured at baseline and after first and 2nd dose. The seropositivity was defined for titers ≥ 7 BAU/mL. The Kruskal-Wallis, post-hoc Dwass-Steel-Critchlow-Fligner pairwise comparisons tests, and multiple linear regression analysis were used. The p-value ≤0.05 was considered significant.Results:A total of 123 volunteers with AID, 37 adults and 86 juvenile AID patients were included in the study.The juvenile group was aged < 18 years (adult 32.5 ±6 vs children group 14.5 ±1.7, p<0.01) and had fewer comorbidities (19 vs. 60%, p<0.01). The groups were homogeneous for sex (female 86% vs. 75%, p=0.23), ethnicity (Caucasians 47 vs. 43%, p=0.7) and degree of immunosuppression (high grade 62 vs. 60%, p=0.25). The frequency of diseases in adults was SLE= 56%, SpA= 5.41%, RA= 5.1%, others= 33.2%; and in children it was SLE= 38.4%, JIA= 41.8, others= 19.7%. The frequency of previous natural exposure to COVID-19 was higher in adults (30.6 vs. 8.1%, p<0.001). Both groups received BNT162b2 vaccine in the 1st. and 2nd. doses and in more than 90% in the 3rd. dose. The frequency of joint paint in post-1st dose (41 vs. 15%, p= 0.003) and in 2nd. dose (24 vs. 0%, p=0.003) was higher in adults. There was no difference in adverse events between the groups after the third dose. The groups were homogeneous for IgG-S titers at baseline. Patients with positive or negative IgG-S at baseline were analyzed separately. There was a significant increase (p<0.001) in IgG-S levels after the 1st, 2nd and 3th doses in the juvenile AID (0.71(0.28-35.07) vs. 443.04 (36.92-2155.77) vs. 2232.38 (1207.43-3688.45) vs. 1920.72 (1383.45-5680.00)), and in the adult group ((1.14(0.14-46.86) vs. 280.17 (49.70-4991.06) vs. 3787.14 (964.28-5680) vs. 2445.24 (868.12-4.418.19)). There was no difference between groups in the 4 times of comparison (p<0.05), regardless of the antibody level at baseline and the degree of immunosuppression. The seroconversion rate was 95% and 100% in both groups, after the 2nd and 3th dose.Conclusion:BNT162b2 vaccine is effective, safe and induced high titles and seroconversion rate in juvenile AID, similar to adults, independent of immunosuppression, comorbidities or previous natural infection. Children showed more joint pain as AE than adults.REFERENCES:NIL.Table 1.IgG-S measurement after vaccination against COVID-19 in baseline, 28 days after 1st dose, 2nd and 3th doseTotalAdultsJuvenilePN=123N=37N=86IgG at inclusion, Median (IQR)0.85 (0.14-46.15)0.71 (0.28-35.07)1.14 (0.14-46.86)0.98IgG 28 days after 1st dose Median (IQR)326.96 (45.16-3887.32)443.04 (36.92-2155.77)280.17 (49.70-4991.06)0.33IgG 28 days after 2nd dose, Median (IQR)3189.32 (965.15-5245.62)2232.38 (1207.43-3688.45)3787.14 (964.28-5680.00)0.14IgG after 3th dose, Median (IQR)2287.78 (888.89-5680.00)1920.72 (1383.45-5680.00)2445.24 (868.12-4418.19)0.67Figure 1.IgG-S measurement after vaccination against COVID-19 in T1(baseline, at inclusion), T2 (28 days after 1st dose), T3 (28 days after 2nd dose) and T3 (28 days after 3th dose).Acknowledgements:We thank Safer Study Group, and the Brazilian Society of Rheumatology for supporting this study. This study was funded by Department of Science and Technology of Federal Government of Brazil.Disclosure of Interests:None declared.

Background:Patients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Individuals with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with comorbidities. In late 2022, the SARS-CoV-2 omicron BA.5 sublineage accounted for most of the sequenced viral genomes worldwide. Bivalent mRNA vaccines contain an ancestral strain component of the new coronavirus plus an updated component of the omicron BA.4 and BA.5. Since February 2023 a single bivalent mRNA vaccine booster dose has been recommended by the Brazilian Ministry of Health for adults who have completed a primary vaccination series and were at high risk of severe disease. However, few studies in the literature assessed the influence of the COVID-19 bivalent vaccine in the composite disease activity indices in patients with RA.Objectives:Evaluate the safety and the influence in the disease activity of a single bivalent mRNA vaccine booster against SARS-CoV-2 in patients with RA.Methods:These data are from the study “Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases (SAFER),” a multicentric observational study that evaluate COVID-19 vaccine in IMRDs in Brazil. This analysis included adults meeting the ACR/EULAR (2010) classification criteria for RA from public’s healthcare centers, undergoing clinical-laboratorial assessments, and having their clinical disease activity indices (CDAI) scores calculated upon study inclusion and 28 days after de vaccination. Adverse events following the vaccination (AEs) were collected from all patients using a diary, filled out daily and returned at the end of 28 days after the booster dose. The Disease activity accessed before and after vaccination was compared using the McNemar test. For all tests, a statistical significance level of 5% and a confidence interval of 95% were used.Results:Of a total of 188 RA patients followed in the study during its primary vaccination schedule, 48 received the bivalent booster and were include in this sub-analysis. Most of them were female (95%), with mean BMI of 27 and an average age of 51 years. The most common comorbidity was hypertension (43%) and obesity (12 %). Only mild and transitory AEs were reported. The more common AEs (Table 1) were pain at the injection (60%), headache and Swelling around the injection site (31%), arthralgia (27%), fatigue (18%), fever (14%), myalgia (14%), nausea (10%) and dizziness (8%). The CDAI were evaluated in 38 individuals. No statistical difference was observed in the proportion of patients achieving treat to target goals (remission or low disease activity) before and after bivalent booster (Table 2).Conclusion:In general, the majority of AEs reported after bivalent COVID-19 booster were mild, similar to the previous data from monovalent immunizing in patients with RA. In the short period of observation, this vaccine did not increase the risk of flare in patients with RA.REFERENCES:[1] Tavares AC, de Melo AK, Cruz VA, de Souza VA, de Carvalho JS, Machado LL, et al. Guidelines on COVID-19 vaccination in patients with immune-mediated rheumatic diseases: a Brazilian Society of Rheumatology task force. Adv Rheumatol. 2022;62:3.Acknowledgements:NIL.Disclosure of Interests:None declared.

The aim of this study was to investigate the effects of multiple cold-water immersions (CWIs) on muscle function, markers of muscle damage, systemic inflammation and ECM degradation following exercise-induced muscle damage (EIMD). Thirty physically active males were randomly assigned to either a control (n = 15) or cold-water immersion (CWI) group (n = 15). The CWI group performed one immersion (10 °C for 20 min) at post-exercise and every 24 h for the following 72 h, while the control group remained in a seated position during these corresponding periods. Muscle strength, vertical jump height, muscle thickness, delayed-onset muscle soreness (DOMS), systemic creatine kinase (CK), C-reactive protein (CRP), inflammatory cytokines and matrix metalloproteinase-2 (MMP-2) activity were assessed at Pre, Post, 24, 48, 72, 96 and 168 h following EIMD. No significant time × group interaction was obtained for muscle strength, vertical jump height recovery and MMP-2 activity (p > 0.05). At 24 h, muscle thickness from the CWI group returned to baseline and was lower than the control (p = 0.04). DOMS returned to baseline at 168 h for the CWI group (p = 0.109) but not for the control (p = 0.008). At 168 h, CK showed a time-group difference with a greater peak for the control group (p = 0.016). In conclusion, multiple CWIs attenuated muscle damage, but not altered systemic inflammation and muscle function recovery.

Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.

The Brazilian Policy of Comprehensive Care for People with Rare Diseases (BPCCPRD) was established by the Ministry of Health to reduce morbidity and mortality and improve the quality of life of people with rare diseases (RD). Several laboratory tests, most using molecular genetic technologies, have been incorporated by the Brazilian Public Health System, and 18 specialised centres have so far been established at university hospitals (UH) in the capitals of the Southern, Southeastern and Northeastern regions. However, whether the available human and technological resources in these services are appropriate and sufficient to achieve the goals of care established by the BPCCPRD is unknown. Despite great advances in diagnosis, especially due to new technologies and the recent structuring of clinical assessment of RD in Brazil, epidemiological data are lacking and when available, restricted to specific disorders. This position paper summarises the performance of a nationally representative survey on epidemiology, clinical status, and diagnostic and therapeutic resources employed for individuals with genetic and non-genetic RD in Brazil. The Brazilian Rare Disease Network (BRDN) is under development, comprising 40 institutions, including 18 UH, 17 Rare Diseases Reference Services and five Newborn Screening Reference Services. A retrospective study will be initially conducted, followed by a prospective study. The data collection instrument will use a standard protocol with sociodemographic data and clinical and diagnostic aspects according to international ontology. This great collaborative network is the first initiative of a large epidemiological data collection of RD in Latin America, and the results will increase the knowledge of RD in Brazil and help health managers to improve national public policy on RD in Brazil.

Fibromyalgia is a polysymptomatic syndrome with a prevalence between 0.2% and 13% of the population and causes work disabilities in approximately half of affected patients. Several treatments to fibromyalgia have been proposed with partial improvement. This study aims to evaluate the efficacy of hyperbaric oxygen therapy and when it should be introduced to fibromyalgia. This is a protocol for an open-label, crossover, randomised clinical trial comparing treatment with hyperbaric oxygen therapy and standardised treatment to fibromyalgia. In the proposed study, 56 individuals with fibromyalgia will be randomised in a 1:1 ratio into a single, fixed, random block, in which one group will receive hyperbaric oxygen therapy and another will receive standard treatment. Subsequently, the groups will be crossed. Participants will be evaluated at baseline, eight and 16 weeks based on functional impairment assessed with the Fibromyalgia Impact Questionnaire-Brazilian Portuguese version, psychopathological symptoms questionnaire and short-form quality of life questionnaire. The improvement of symptoms concerning the moment of therapy used will be compared between groups. For sample size calculation, a moderate effect size, 80% power and 95% CI will be estimated, in a total of 46 patients. Considering a dropout of 20%, 56 patients should be recruited. The study was approved by the Universidade Federal de Juiz de Fora Teaching Hospital ethics committee and assigned the number 53058421.9.0000.5133 (version 3). The results will be disseminated via publications in peer-reviewed journals and presentations in medical meetings. RBR-6prps8g)/UTN U1111-1278-3224.

Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T 0 ). The median age at diagnosis was 58 years, and time from diagnosis to T 0 was 3.3 years. Following T 0 , 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0–8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T 0 in 94 patients (44%) including ⩾partial response in 69 (32%). The median overall survival and event-free survival from T 0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs.