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BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease, which presents an immune disorder that leads to the production of autoantibodies with potential involvement of multiple organs. Infections are one of the most frequent causes of hospitalization and death in lupus patients, and SARS-CoV-2 infection has been a global threat since March 2020. Immunization of these patients has been strongly recommended, although vaccine evaluation studies have not included this profile of patients.ObjectivesTo evaluate the immunogenicity and safety after 2 doses of the vaccine against SARS-CoV2 in patients with SLE.MethodsSubgroup of SLE patients from the prospective multicenter cohort of patients with immune-mediated diseases "SAFER” – Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease, a phase IV study. Vaccination against SARS-CoV-2 took place with vaccines approved by Brazilian regulatory bodies CoronaVac (Inactivated SARS-CoV-2 Vaccine), ChadOx-1 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) and this project followed in line with the guidelines of the National Immunization Plan in Brazil. Patients aged 18 years or older with a previous diagnosis of SLE (according to the 2019 ACR/EULAR criteria) were included. Patients were evaluated by telephone contact and in a face-to-face visit on the 28th day after each dose. Patients were followed up by means of blood collection for measurement of IgG antibody against SARS-COV-2 by chemiluminescence and disease activity assessed using SLEDAI-2K score.ResultsA total of 367 individuals with SLE were included, of whom 207 received 2 doses of CoronaVac, 128 received 2 doses of ChadOx-1 and 32 received 2 doses of BNT162b2. 90% of the subjects were female with a mean age of 37 years. About 42% (154) of the individuals included did not have any other associated comorbidity. 50% (182) of patients were using oral glucocorticoids and azathioprine was the most frequent immunosuppressive therapy. Regarding disease activity parameters, 38% (140) of patients had zero SLEDAI-2K at baseline and 41% (147) had zero SLEDAI-2K 28 days after the 2nd dose. Anti-DNA positivity was 30.7% (16/52) at inclusion and 32.6% (17/52) 28 days after the 2nd dose. Complement consumption was present in 18% (10/55) at inclusion and in 14.5% (8/55) 28 days after the 2nd vaccine dose. The geometric mean titers of IgG antibodies against SARS-COV-2 increased in the different vaccine groups, log 2.27 BAU/mL at inclusion and log 5.58 BAU/mL 28 days after the 2nd dose. Antibody titers after second dose varied between different vaccines, 4.96 BAU/mL CoronaVac, 6.00 BAU/mL ChadOx-1 and 7.31 BAU/mL BNT162b2 vaccine, p < 0.001. Only 3.54% (13/367) patients had covid-19 infection after the 15th day of the second dose of immunization, 9 of them having received 2 doses of CoronaVac, 4 of them of ChadOx-1 and none of them receiving BNT162b2, with p-value of 0.63.ConclusionThis study suggests that vaccines against SARS-COV-2 are safe in SLE patients. Induction of immunogenicity occurred in different vaccine regimens. Only 3.5% of individuals had COVID-19 infection with no difference between the types of vaccines evaluated. Future analyzes to explore the association of the effect of immunosuppressive medication, as well as the impact of booster doses and longer follow-up on clinical outcome will be performed.References[1]Mason A, et al. Lupus, vaccinations and COVID-19: What we know now. Lupus. 2021;30(10):1541-1552.[2]Furer V, Eviatar T, Zisman D, et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: A multicentre study. Ann Rheum Dis. 2021;80(10):1330-1338.[3]Izmirly PM, Kim MY, Samanovic M, et al. Evaluation of Immune Response and Disease Status in SLE Patients Following SARS-CoV-2 Vaccination. Arthritis Rheumatol. Published online 2021.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with comorbidities associated. However, few studies in the literature assessed the safety and immunogenicity of the COVID-19 heterologous vaccine schedules in patients with RA.ObjectivesEvaluate the safety and immunogenicity of two heterologous vaccine schedules against SARS-CoV-2 in patients with RA.MethodsThese data are from the study "SAFER - Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases,” a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Immunogenicity and adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 plus additional dose of BNT162b2 or after two doses of inactivated SARS-CoV-2 vaccine CoronaVac plus additional dose of BNT162b2. The titers of neutralizing antibodies against the receptor-biding domain of protein spike (S) of SARS-CoV-2 (anti-RBD) were measured by chemiluminescence test after each dose of immunizers. Proportions between groups were compared using the chi-square and Fisher's exact tests for categorical variables. Clinical Disease Activity Index (CDAI) before and after vaccination was assessed using the McNemar test.ResultsA total of 107 patients with RA were include in the study, most of them female, with a mean age of 46 years. Biological disease modifying anti-rheumatic drugs (DMARDs) were used by 50 % of the patients and conventional synthetics DMARDs in 48 %. Two doses of CoronaVac plus additional dose of BNT162b2 was used in 66 patients and two doses of ChAdOx1 plus additional dose of BNT162b2 in 41. Only mild AEs were observed, mainly after the first dose. The most common AEs after all doses, regardless of the immunizer type, were pain at the injection, headache, arthralgia and myalgia. ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0,001) and arthralgia (68% vs 15%, p < 0,001) compared to CoronaVac. No patients had flare after the vaccination. The titers of anti-RBD after two doses of ChAdOx1 were higher compared to two doses of CoronaVac (6,03 BAU/mL vs 4,67 BAU/mL, p < 0,001). However, after the additional dose of BNT162b2, the anti-RBD titers were similar in both groups (7.28 BAU/mL vs 7.06 BAU/mL, p = 0.56). Only two cases of COVID 19, with mild symptoms, were reported, one in each group.Figure 1.ConclusionChAdOx1, CoronaVac, and BNT162b2 vaccines are safe in RA patients. The frequency of local adverse effects, particularly pain at the injection site, is high. AEs are more frequent with ChAdOx1, especially after the first dose. The use of the immunizers does not change the degree of inflammatory activity of the disease. The immunogenicity of the two heterologous regimens analyzed was similar.References[1]Marques C, Kakehasi AM, Gomides APM, Paiva EDS, Dos Reis Neto ET, Pileggi GCS, et al. A Brazilian Cohort of Patients With Immuno-Mediated Chronic Inflammatory Diseases Infected by SARS-CoV-2 (ReumaCoV-Brasil Registry): Protocol for a Prospective, Observational Study. JMIR Res Protoc.[2]Medeiros-Ribeiro AC, Aikawa NE, Saad CGS, Yuki EFN, Pedrosa T, Fusco SRG, et al. Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial. Nat Med. 2021;27(10):1744-1751.[3]Machado PM, Lawson-Tovey S, Strangfeld A, Mateus EF, Hyrich KL, Gossec L, et al. Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry. Ann Rheum Dis. 2022;81(5):695-709.[4]Tavares ACFMG, Melo AKG, Cruz VA, Souza VA, Carvalho JS, Machado KLLL, et al. Guidelines on COVID-19 vaccination in patients with immunemediated rheumatic diseases: a Brazilian Society of Rheumatology task force. Adv Rheumatol. 2022;62:3.Acknowledg ments:NIL.Disclosure of InterestsNone Declared.
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Objectives: Patients with Systemic Lupus Erythematosus (SLE) are predisposed to serious infections due to immunocompromise, comorbidities, immunomodulatory and/or immunosuppressive therapy, as well as the lack of these medications faced by patients dependent on the Sistema Unico de Saude (SUS) during the COVID-19 pandemic. Studies revealed a low risk of worsening disease activity after vaccination against SARS-CoV-2 and safety in the continuity of immunomodulatory therapy during the vaccination stages. Thus, immunization against COVID-19 is an important pillar in reducingmorbidity and mortality related to infectious conditions and SLE. This study had the objective to understand the disease activity in SLE patients after vaccination against COVID-19. Method(s): This is an observational, longitudinal, ambidirectional study with follow-up of subgroups of patients with immune-mediated rheumatic diseases immunized with vaccines made available by the Programa Nacional de Imunizacao (Butantan Institute, Pfizer/BioNTech, BioManguinhos/Fiocruz and Janssen). Data from the SLE disease activity index 2000 (SLEDAI-2 K) and sociodemographic data were collected and stored via an online platform, with a comparison of the index before and after each dose. This study was approved by the local Research Ethics Committee, and it is associated to the SAFER Project from Brazilian Society of Rheumatology. Result(s): A total of 223 patients were included, of which 83% were female and 39% had SLE, 36.7 +/- 11.76 years old. Regarding the disease activity, at inclusion the mean PGA score(SD) was 2,61 +/- 2,77. After the 1st dose it was 1.38 +/- 2.17, after the 2nd dose it was 2,35 +/- 2,99, after the 3rd dose it was 2,19 +/- 2,58 and after the 4th dose 1.18 +/- 1.88. The mean SLEDAI-2 K score at inclusion was 7,27 +/- 9,70, after the 1st dose it was 2,75 +/- 5,29, after the 2nd dose it was 4,73 +/- 6,40, after the 3rd dose 3,33 +/- 5,51 and after the 4th dose 2.12 +/- 4.27. 6% of the patients referred worsening disease activity after the 1st dose, 14,3%after the 2nd dose, and no patient reportedworsening of disease activity after the 3rd and 4th doses. Conclusion(s): Vaccination did not contribute toworsening disease activity of the SLE patientss studied, according to the indices used to assess disease activity.
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Objectives: Immunization against SARS-CoV-2 is an effective strategy to reduce morbidity and mortality in the face of the COVID-19 pandemic. People with Immune-mediated Rheumatic Diseases (IMRD) also benefited from this campaign. However, there is a limited amount of data on the outcome of vaccination in these patients, in terms of those who were infected by the virus. This study had the objective to evaluate the rate of COVID-19 cases in patients with IMRD after vaccination against SARS-CoV-2. Method(s): Observational, longitudinal and ambidirectional study with follow-up of subgroups of patients with IMRD immunized with vaccines made available by the National Immunization Plan (inactivated adsorbed vaccine registered by the Instituto Butantan (IB), recombinant vaccines registered by Bio Manguinhos/ Fiocruz and by Janssen, and Pfizer/BioNTech). Sociodemographic data and questionnaires on flu syndrome, laboratory confirmation of infection and need for hospitalization and outcomes were collected and stored via an online platform. This study is associated to the SAFER Project from the Brazilian Society of Rheumatology and it was approved by the local Research Ethics Committee. Result(s): A total of 223 patients aged over 18 years, mean age 42.79 +/- 15.18 years, were included. All were within the inclusion/exclusion criteria, with 83% being female. The main IMRD included were systemic lupus erythematosus (39%) and rheumatoid arthritis (33.6%). After the 1st dose, 1.45% of patients had COVID-19, 50% sought health services (emergency care), without the need for hospitalization and after the 2nd dose, 1.5% had the disease, of which none sought health services, required hospitalization or had a negative outcome. After the 3rd dose,: 2.9%were infected with SARS-CoV-2 one month later, 15.6% two to three months later and 5.5% four to six months later, all with laboratory confirmation;only 4% presenting any serious complication;there were no deaths. After the 4th dose, 9.1%of patients had COVID-19, of which 40%were hospitalized, without the need for assisted ventilation;half of these patients had a serious complication, but there no deaths. Conclusion(s): In this study, we observed the effectiveness of the vaccine in preventing severe cases of COVID-19 and complications of SARS-CoV-2 infection.
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Objectives: Chronic Inflammatory Immune-mediated Diseases (CIMD) can cause pain and severe discomfort to the patient, leading to significant reductions in his/her quality of life. Vaccination against COVID-19 has proven to be an efficient method in preventing cases and serious repercussions. However, there is insufficient evidence on the safety of these vaccines in the CIMD population. Objective(s): To assess disease activity in adolescent patients with CIMD after vaccination against SARS-CoV-2. Method(s): Observational, longitudinal, ambidirectional study with follow-up of groups of adolescent patients with CIMDwho received the vaccine provided by the National Immunization Program -Pfizer/BioNTech. Sociodemographic and clinical disease activity data were collected before and after each vaccine dose. Data were stored through an online platform (REDCap). This study is associated to the SAFER Project from the Brazilian Society of Rheumatology and was approved by the local Research Ethics Committee. Result(s): Nineteen adolescents aged between 12 and 17 years were included, all of whom met the inclusion/exclusion criteria. Of the total, 31.6% have Juvenile Idiopathic Arthritis (JIA)-14.33 +/- 2.25 years of age, whose subtypes included persistent oligoarticular JIA (16.7%), Polyarticular Rheumatoid Factor (RF) negative (33.3%), Polyarticular RF positive (16.7%) and Systemic (33.3%);68.4% have Systemic Lupus Erythematosus (SLE) -14.77 +/- 1.96 years of age. Regarding JIA patients, at inclusion, the mean disease activity assessed by the physician was 3 +/- 3.83 and 3.25 +/- 3.77 as assessed by the patient. After the 1st dose, the mean activity assessed by the physician was 2.8 +/- 3.9 and after the 2nd dose it was 3 +/- 4.24. Themean activity after the first dose as assessed by the patient was 3.2 +/- 3.96, and after the 2nd dose it was 2.8 +/- 3.11. In the SLE patients, at inclusion, the mean degree of disease activity was 1.92 +/- 1.83 and of the SLEDAI-2 K was 4.67 +/- 5.14. After the 1st dose, the mean disease activity was 1.11 +/- 1.96, and after the 2nd dose, it was 2.25 +/- 2.76. After the 1st dose, the SLEDAI-2 K was 1.11 +/- 1.76, and after the 2nd dose it was 4.25 +/- 5.28. No reports of worsening of disease activity after the vaccine were found. Conclusion(s): The vaccination proved not to contribute to worsening of clinical activity of rheumatic diseases in adolescents, without significant changes in SLE assessment indices and in the personal and medical assessment of JIA patients.
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Objectives: In the Chronic Inflammatory Immune-mediated Diseases (CIMD), infections mainly occur in the respiratory tract and their occurrence is related to drug-induced immunosuppression, underlying diseases and comorbidities. To reduce this morbidity and mortality, vaccination is an effective means of prevention. However, the available studies on SARS-CoV-2 vaccines have not addressed this group of patients with CIMD, and there are still many doubts regarding the indications, adverse effects, safety and efficacy of these vaccines. Objective(s): to evaluate the adverse effects of vaccines against SARS-CoV-2 in adolescent patients with CIMD. Method(s): Research associated to the SAFER Project from Brazilian Society of Rheumatology. It is an observational, longitudinal, ambidirectional study, with follow-up of groups of vaccinated adolescent patients with CIMD, vaccine by Pfizer/BioNTech. Sociodemographic data were collected, stored on an online platform, and adverse events were presented by filling in diaries issued for each patient. This study was approved by the local Research Ethics Committee. Result(s): We included 19 adolescents, aged between 12 to 17 years, who met the inclusion and exclusion criteria. The mean age was 14.63 +/- 2.01 years. Of these, 68.4% were female. In relation to CIMD, 31.6% have Juvenile Idiopathic Arthritis and 68.4% have Systemic Lupus Erythematosus. All were vaccinated with the Pfizer vaccine. In the 1st dose, the main adverse effects presented were Pain at the injection site (85.7%), Headache (42.9%), Tiredness (33.3%) and Edema and skin induration at the injection site (26, 7%). After the 2nd dose, the only adverse effect reported was Pain at the injection site (57.1%), with no other complaints. Conclusion(s): The adverse effects reported are of mild tomoderate reactogenicity;no serious adverse events were reported.
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Objectives: To evaluate the safety and immunogenicity of CoronaVac and ChAdOx1 vaccines against SARS-CoV-2 in patients with Rheumatoid Arthritis (RA). Method(s): These data are from the 'SAFER (Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases)' study, a Brazilian multicentric longitudinal phase IV study to evaluate COVID-19 vaccine in immunomediated rheumatic diseases (IMRDs). Adverse events (AEs) in patients with RA were assessed after two doses of ChAdOx1 or CoronaVac. Stratification of postvaccination AEs was performed using a diary, filled out daily. The titers of neutralizing antibodies against the receptor-biding domain of SARS-CoV-2 (anti-RBD) were measured by chemilumine scence test after each dose of immunizers. Proportions between groups were compared using the Chi-square and Fisher's exact tests for categorical variables. Clinical Disease Activity Index (CDAI) before and after vaccination was assessed using the McNemar test. Result(s): A total of 188 patients with RA were included in the study, most of them were female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed. The more common AEs after the first dose were pain at injection site (46,7%), headache (39,4%), arthralgia (39,4%) and myalgia (30,5%), and ChAdOx1 had a higher frequency of pain at the injection site (66% vs 32 %, p alpha 0.001) arthralgia (62% vs 22%, p alpha 0.001) and myalgia (45% vs 20%, p alpha 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection site (37%), arthralgia (31%), myalgia (23%) and headache (21%). Arthralgia (41,42 % vs 25 %, p = 0.02) and pain at injection site (51,43% vs 27%, p = 0.001) were more common with ChAdOx1. No patients had a flare after vaccination. The titers of anti-RBDafter two doses of ChAdOx1 were higher compared to two doses of CoronaVac (6,03 BAU/mL vs 4,67 BAU/mL, p alpha 0,001). Conclusion(s): The frequency of local adverse effects, particularly pain at injection site, was high. AEs were more frequent with ChAdOx1, especially after the first dose. The use of the immunizers dis not change the degree of inflammatory activity of the disease. In patients with RA, ChAdOx1 was more immunogenic than CoronaVac. .
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Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease which presents infections as one of the most frequent complications, including more severe outcomes of Coronavirus disease 2019 (COVID-19). Immunization of these patients has been strongly recommended, however, data on safety are still scarce. In this study we evaluate the safety after vaccination against SARS-CoV2 in patients with SLE. Method(s): Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease - the 'SAFER' study, is a longitudinal Brazilian multicenter phase IV study. In this study patients with SLE (according to the 2019 ACR/EULAR criteria), older than 18 years who received vaccination against SARS-CoV-2 CoronaVac (Inactivated SARS-CoV-2 Vaccine), ChadOx-1 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) were included. The evaluation of adverse events (AEs) was done by telephone contact, symptom diaries and a face-to-face visit on the 28th day after each dose. Patients were followed up also by disease activity, assessed using SLEDAI-2 K score. Result(s): A total of 367 individuals with SLE were included, 207 received CoronaVac, 128 received ChadOx-1 and 32 received BNT162b2. Ninety percent of the subjects were female with a mean age of 37 years. About 50% (182) of patients were using oral glucocorticoids and azathioprine was the most frequent immunosuppressive therapy. Regarding disease activity parameters, 38%(140) of patients had zero SLEDAI-2Kat baseline and 41%(147) had zero SLEDAI-2 K 28 days after the 2nd dose. After the first and second dose the most frequent AEs were pain at injection site (58%/44%), headache (48%/33%) and pruritus (42%/37%). Comparing the three vaccines, after the first dose, local symptoms, myalgia, and fever were less frequent in patients who received CoronaVac (p alpha 0.001) as well as headache, tiredness (p = 0.001) and arthralgia (p = 0.003). After the second dose, only local symptoms such as pain at the application site and thickening of the skin around the application site were less frequent in the CoronaVac group (p alpha 0.05). Headache, tiredness, musculoskeletal symptoms and fever were more common in patients receiving AstraZeneca. No serious adverse events were reported regardless of the vaccination schedule used. Conclusion(s): This study suggests that vaccines against SARS-COV-2 are safe in SLE patients. Neither severe AEs were reported nor worsening of disease activity were reported. Comparing the different vaccines, CoronaVac had fewer adverse events.
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Objectives: To evaluate the immunogenicity of ChAdOx1, Coronavac and BNT162B2 vaccines in SLE patients, including homologous and heterologous immunizations. Method(s): The 'Safety and efficacy on COVID-19 Vaccine in Rheumatic Disease-SAFER study' is a Brazilian multicentric longitudinal phase IV study to evaluate COVID-19 Vaccine in immune-mediated rheumatic diseases (IMRD) in real life, started on May 2021. SLE patients (according to the 2012 SLICC classification criteria), older than 18 years of age were recruited after 2 or 3 doses of vaccine against COVID-19 (ChAdOx1, BNT162b2 and CoronaVac) and were evaluated at baseline and on the 28th day after each dose. Homologous immunization was considered if they received three doses of the same vaccine and heterologous if a different one was applied. IgG antibody against SARS-CoV-2 spike receptor-binding domain were measured by chemiluminescence (SARS-CoV-2-IgG-II Quant assay, Abbott-Laboratories) at baseline and 28 days after the first, 2nd and 3rd doses (Seropositivity IgGSpike>= 7.1BAU/mL). Statistical analysis: ANOVA and pairwise comparisons tests Results: 316 SLE patients were included (255 heterologous and 61 homologous immunization), 89.2% were female and the mean age was 37.6 +/- 11.2 years. The two groups were homogeneous regarding demographical data, disease activity and immunosuppressive treatment. 49.7% used corticosteroids (alpha 5 mg/day in 52.3%), 83.5% antimalarials, 22.8% azathioprine and 20.3% mycophenolate mofetil. 207 patients received the first two doses with CoronaVac, 128 ChadOx-1 and 32 BNT162b2. Regarding the first two doses of the same vaccine, there was no difference in IgG titers over time between CoronaVac or ChadOx-1 (p = 0.313). IgG titers increased in all vaccine groups, with difference only after 2nd dose: 4.96 +/- 1.71BAU/mL CoronaVac vs. 6.00 +/- 1.99BAU/mL ChadOx-1 vs. 7.31 +/- 1.49BAU/mL BNT162b2 (p alpha 0.001). There was no difference in IgG titers over time between homologous or heterologous vaccine schedule (p = 0.872). IgG titers also increased in all groups, with difference only after 2nd dose: 5.49 +/- 1.96BAU/mL heterologous vs. 6.30 +/- 2.10BAU/mL homologous (p = 0.009). Conclusion(s): Induction of immunogenicity occurred in different vaccine regimens in SLE patients. Future research to explore different heterologous schemes in IMRD must be performed.