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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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BackgroundThe COVID-19 pandemic has brought uncertainties to rheumatology practice, mainly related to the possibility of triggering disease activity after infection in immune mediated rheumatic diseases (IMRD). To date, there are few data in the literature specifically evaluating this issue.ObjectivesEvaluate the disease activity in IMRD patients after 6 months of the infection, compared to pre infection status.MethodsReumaCoV Brasil is a longitudinal study performed at 35 study centers designed to follow-up IMRD patients for 6 months after clinical or laboratorial COVID-19 diagnosis (cases), comparing with patients with IMRD who had not had the infection at the time of inclusion (controls). Demographic data such as age, sex, comorbidities, clinical characteristics, treatment, evolution of COVID-19 and disease activity status were collected using a Research Eletronic Data Capture (REDCap) database on three consecutive visits (inclusion and 6 months). The analysis was carried out on the four diseases with the highest inclusion number in the study: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). In addition to specific disease activity assessment metrics, we used patient's global assessment of disease activity (PGA), ranging from 0 to 10, at all visits, with 0 being no activity and 10 being intense activity. All conclusions were drawn considering the significance level of 5%. This study was registered at the Brazilian Registry of Clinical Trials—REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.ResultsBetween May 2020 and January 2021, 2032 patients were included in the registry, and of these, 1322 patients (721 cases and 601 controls), completed 6 months of follow-up, being 550 SLE (42.0%), 497 RA (37.6%) and 176 SpA (13.3%) and 99 (7.4%) PsA. Most patients were female (82.0%);the median age was 46.7 (13.8). Disease activity at the time of enrollment, according to the PGA, was similar between cases and controls, except for patients with RA and AS, where it was higher in controls. After the follow up time, no worsening of activity was observed in any of the diseases evaluated in the case group (Table 1). Despite this, worsening of disease symptoms after COVID-19 was reported by 23.3%, 24.6%, 25.0% and 25.8% of patients with SLE, RA, AS and PsA respectively, not related with disease activity.ConclusionIn patients with IMRD, no worsening of disease activity was observed after COVID-19 in this cohort of Brazilian patients. Despite this, many patients noticed worsening of symptoms, possibly associated not with the triggering of the activity, but with the so-called long COVID syndrome.Table 1.Comparison of disease activity, according to PGA, comparing disease activity status at inclusion and after 6 months of follow up, in cases and controlsINCLUSIONAFTER 6 MONTHSCasesControlsp-valueCasesControlsp-valueSLE2 (0-4,5)2 (0-4)0,8102 (0-5)2 (0-4)0,172RA3 (1-5)4 (2-6)0.0013 (1-5)3 (1-5,5)0,731AS2 (0-5)4 (1-6)0,0022 (0-5)3,5 (1-6)0,044PsA2 (0-4)2 (0-5)0,8162 (0-5)2 (0-5)0,939*Median and interquatile range;Student t test;CI 95%AcknowledgementsReumaCoV Brasil researchers, Brazilian Society of Rheumatology and National Council for Ccientific and Technological Development.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: Few studies evaluate the immunogenicity and safety of different COVID-19 vaccine platforms in patients with primary Sjogren's Syndrome (pSS). The present study aims to assess the immunogenicity through anti-spike IgG antibodies after the COVID-19 vaccine dose in heterologous groups compared to homologous regimen in patients with pSS. Method(s): These data are from the SAFER study: 'Safety and efficacy of the COVID-19 vaccine in rheumatic disease', a real-life phase IV multicenter longitudinal study, evaluating patients since before the first dose. Pregnant women, those with a history of serious adverse events prior to any vaccine, and those with other causes of immunosuppression were excluded. Patients with pSS > 18 years, classified according to ACR/EULAR 2016 classification criteria were included. Antibodies against the Receptor Binding Domain - RBD portion of the Spike protein of SARS-CoV-2 (IgG-S) were measured by chemiluminescence (Architect SARS-CoV-2 Quanti II, Abbott), before the first dose and 28 days after the 2nd and 3rd dose. Seropositivity was defined as IgG-Spike titers >=7.1 BAU/mL. Patients received adenoviral vector (ChAdOx1, Astrazeneca), mRNA (Pfizer) or inactivated SARS-COV-2 (Coronavac). Non-parametric methods were used. The alpha level of significance was set at 5%. Result(s): 56 participants received 3 doses, 46 +/- 11 years old, disease duration 7.62 years, 92.9% female, 41.1% White and 55.4% Mixed. The homologous third-booster dose group (n = 15, all ChAdOx1) and heterologous group (n = 41) were homogeneous for age, sex, ethnicity, comorbidities, medication and baseline IgG-S median [IQR] titers. After primary vaccination (2 doses) IgG-S median and titers [IQR] were similar in homologous and heterologous groups (373.03 [179.58, 843.92] vs. 473.36 [119.05, 1059.60], p = 0.705). Third-booster dose induced higher IgG-S median [IQR] titers compared to only 2 doses (1229.54 [333.55, 4365.47] vs 464.95 [140.42, 1015.25], p alpha 0.001). Heterologous 3rd-booster induced higher IgG-S median [IQR] titers than homologous scheme with ChAdOx1 (1779.52 [335.83, 4523.89] vs 730.76 [303.37, 1858.98], p = 0.150), Fig 1 and 2, although not statistically significant. Conclusion(s): Third booster dose induced higher humoral immune response compared to two doses whichmay improve protection against COVID-19 in patients with pSS. Although not statistically significant, the response to the heterologous scheme tended to be better than the response to the homologous booster vaccination, which heterologous booster scheme tended to respond better than homologous booster vaccination, which is relevant in this immunosuppressed population. Increasing the sample size will help clarify this issue. .
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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: Patients with immune-mediated rheumatic diseases (IMRDs) develop more severe outcomes of Coronavirus disease 2019 (COVID-19). Recent studies have contributed to understand the safety and efficacy of COVID-19 vaccines in IMRDs, suggesting that different diseases and therapies may interfere on immunization efficacy. In this study we analyze the immunogenicity of COVID-19 vaccines in patients with Systemic Vasculitides (VASC), the rate of COVID-19 and the frequency of disease relapse following immunization. Method(s): We included patients with VASC (n = 73), a subgroup of the SAFER study (Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease), a longitudinal, multicenter, Brazilian cohort.We analyzed the geometric means of IgG antibody against receptor-biding domain of protein spike of SARS-CoV-2 (anti-RBD) after two shots of CoronaVac (Inactivated vaccine), ChadOx-1 (AstraZeneca) or BNT162b2 (Pfizer-BioNTech). IgG anti-RBD was measured by chemiluminescence test. We assessed new-onset COVID-19 episodes, adverse events (AE) and disease activity for each VASC. Result(s): The sample included Behcet's disease (BD) (n = 41), Takayasu arteritis (TAK) (n = 15), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (n = 14), polyarteritis nodosa (n = 7) and other small vessel VASC(n = 6). The majority of patients were female (69%) without comorbidities (49%) and a median age of 37 years. The most common medication was conventional synthetic disease-modifying anti-rheumatic drugs, followed by biologic drugs. No patient received rituximab at baseline. Most patients received CoronaVac (n = 25) or ChadOx-1 (n = 36), while four received BNT162b2. Baseline IgG-RBD means were 1.34 BAU/mL. They increased to 3.89 and 5.29 BAU/mL after the 1st and 2nd vaccine dose, respectively. ChadOx-1 had higher antibody titers than CoronaVac (p = 0.002). There were no differences between different VASC. There were 3 cases of COVID-19 after immunization with CoronaVac. BD patients had a tendency for more cutaneous-articular activity following ChadOx-1. There were no severe relapses and no serious adverse events. Conclusion(s): Our results show the safety of different SARS-CoV-2 vaccines in VASC population. A progressive increase of IgG-RBD antibodies was observed after each dose. ChadOx-1 led to higher IgG-RBDgeometricmeans compared toCoronaVac. Finally, even though ChadOx-1 presented a tendency of triggering mild disease activity, there were no significant disease activity following vaccination in VASC patients. .
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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: The use of glucocorticoids (GC) has been associated with increased risk of hospitalization for coronavirus infection and reduced immunogenicity of SARS-CoV-2 vaccines in immune-mediated diseases (IMD) patients. However, there is still controversy of which dose of GC is correlated with impaired vaccine response on each of the diverse COVID-19 vaccines available, as well as the possible influence of other concurrent immunosuppressants. This study aimed at evaluating the effect of GC on serological response after two doses of BNT162b2 (Pfizer/BioNTech), CoronaVac (inactivated SARS-CoV-2 Vaccine) and ChadOx1 (AstraZeneca) and after the booster dose in patients with IMD. Method(s): The data were extracted from a multicenter longitudinal observational Brazilian cohort (SAFER: Safety and Efficacy on COVID19 Vaccine in Rheumatic Disease). Patients >18 years of age with IMD were evaluated after 2 doses of the same vaccine against COVID-19 and after a booster vaccine, applied according to Brazilian National Immunization Program. All patients underwent clinical examination and collected blood samples for immunogenicity tests. Serological response was evaluated by Anti-RBD titers (IgG) at baseline and 4 weeks after each vaccine dose. Result(s): Among the 1009 patients evaluated, 301 were using GC (196/401 SLE, 52/199 RA and 27/74 vasculitis). Patients using GC were younger (38.2 vs 40,8 years, p = 0,002), had higherBMI (27,6 vs 26,4 p = 0,008), higher prevalence of kidney disease (3,3% vs 0,5%, p = 0,001) and of thrombosis (11,6% vs 5,9%, p = 0,002) than non-users. Regarding the type of vaccine, most of the GC users received CoronaVac (61.7%), while only 31.9%of non-users received this vaccine (p alpha 0.001). Although there were similar rates of pre-vaccination infections among them, patients with GC tended to have a higher incidence of confirmed COVID-19 infection after the 2nd dose of the vaccine compared to non-users (4.5% vs 2.0% p = 0.054). The antibody titers after the 1st dose of COVID-19 vaccines were similar between groups, but there was a worse response in the GC group after the 2nd dose (p = 0.039). However, this difference was not statistically significant after the 3rd dose (Figure). Conclusion(s): GC use may compromise vaccine-induced immunogenicity after a 2-dose regimen;however, this effect does not remain significant after the booster dose. Multivariate analysis is still pending to assess the potential difference in the impact of GC on the immune response depending on GC dose, type of vaccine and associated drugs.
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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.
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Objective To evaluate the incidence of COVID-19 and its main outcomes in rheumatic disease (RD) patients on hydroxychloroquine (HCQ) compared to household cohabitants (HC).Methods This is a 24-week nationwide prospective multi-centre cohort with a control group without RD and not using HCQ. All participants were monitored through scheduled phone interviews performed by health professionals. Details regarding COVID-19 symptoms, and epidemiological, clinical, and demographic data were recorded on a specific web-based platform. COVID-19 was defined according to the Brazilian Ministry of Health criteria and classified as mild, moderate or severe.Results A total of 9,585 participants, 5,164 (53.9%) RD patients on HCQ and 4,421 (46.1%) HC were enrolled from March 29th, 2020 to September 30th, 2020, according to the eligibility criteria. COVID-19 confirmed cases were higher in RD patients than in cohabitants [728 (14.1%) vs. 427 (9.7%), p<0.001] in a 24-week follow-up. However, there was no significant difference regarding outcomes related to moderate/ severe COVID-19 (7.1% and 7.3%, respectively, p=0.896). After multiple adjustments, risk factors associated with hospitalisation were age over 65 (HR=4.5;95%CI 1.35-15.04, p=0.014) and cardiopathy (HR=2.57;95%CI 1.12-5.91, p=0.026). The final survival analysis demonstrated the probability of dying in 180 days after a COVID-19 diagnosis was significantly higher in patients over 65 years (HR=20.8;95%CI 4.5-96.1) and with 2 or more comorbidities (HR=10.8;95%CI 1.1-107.9 and HR=24.8;95%CI 2.5-249.3, p=0.006, respectively).Conclusion Although RD patients have had a higher COVID-19 incidence than individuals from the same epidemiological background, the COVID-19 severity was related to traditional risk factors, particularly multiple comorbidities and age, and not to underlying RD and HCQ.
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Introduction. There are few studies that evaluated the response to Covid- 19 vaccines, in primary Sjogren's Syndrome (pSS) and none evaluated ChAdOx1 n-Cov19 (AstraZeneca/Fiocruz). The aim of this study was to evaluate the efficacy and safety of the ChAdOx1 n-Cov19, a viral vector vaccine, in pSS compared to healthy control (HC). Methods. Patients with pSS >18 years, classified according to ACR/EULAR 2016 were included. Neutralizing antibodies against the Receptor Binding Domain - RBD portion of the Spike protein of SARS-CoV-2 (IgGS) were measured by chemiluminescence (Abbott), before the first dose (D0) and 28 days after the second dose (D28*). The test is considered reactive if >50 AU/ml. Results. Sixty pSS patients and 62 HC were recruited from a single center (HUCAM-UFES, Vitoria, ES, Brazil). The HC group was homogeneous for sex (92% women) and younger than HC (47+/-11 vs. 39+/-13, p<0.05). In the pSS group, 45.2% were anti-Ro positive, mean ESSDAI was 3.2, 83.3% were using DMARD or immunosuppressant/biological therapy, 31.9% were in high immunosuppression. The frequency of mild adverse events (AE) was similar in both two groups. No serious AE, hospitalizations or death were reported. There was no difference between the PGA ("Patient's Global Assessment") after vaccination (4.5 vs.5, p=0.903). Among seronegative individuals at baseline, the seroconversion rate (100% vs. 89%, p=0.02) was lower, and geometric mean titers (GeoMean IgG-S) was similar in pSS=696.9(CI95%237.6 -2,043) compared to HC=1,986(CI95%1,463-2,697;p=0.316). However, in those with high immunosuppression, the seroconversion (71%, p=0.001) and GeoMean titers were lower 229.4 (CI95%14.64-3,594, p=0.004). Patients in moderate to high disease activity (ESSDAI >=5) showed lower seroconversion (60%, p=0.006) and Geomean titers 31.7 (CI95%0.06-15.4;p=0.004). Conclusions. ChAdOX1 vaccine is safe and induced high GeoMean neutralizing antibodies titers and seroconversion rate in pSS patients similar to HC. Immunossuppression therapy and disease activity decreased the immune response to the vaccine.
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Objectives. To investigate the safety and efficacy of SARS-Cov-2 vaccination in a large international cohort of patients with primary Sjogren syndrome due to scarcity of data in this population. Methods. By the first week of May 2021, all Big Data Sjogren Consortium centers had been contacted and asked for Registry patients to be included in the study if they had received at least one dose of any SARS-CoV-2 vaccine. The in-charge physician asked patients about local and systemic reactogenicity, using a pre-defined electronic questionnaire to collect epidemiologic data, COVID 19 vaccination data, and COVID 19 vaccination side effects. Adverse events were defined as those reported by the patient at the site of injection within 7 days from vaccination (reactogenicity) as local adverse events, systemic symptoms as systemic side effects, and postvaccination AEs of special interest related to SS as SS flares. Results. The vaccination data of 1237 patients (1170 women, with a mean age at diagnosis of primary SjS of 50.5 13.2) were received. A total of 835 patients (67 percent) reported any adverse event, including local (53 percent) and systemic (50 percent) AEs. Subjective symptoms (63%) were the most common local AEs, followed by objective signs at the injection site (16%) and general symptoms were the most commonly reported systemic AEs (46 percent), followed by musculoskeletal (25 percent), gastrointestinal (9 percent), cardiopulmonary (3 percent), and neurological (2 percent). People under 60 years old had a higher risk of developing AE after vaccination (OR 2.48, CI 95 1.89-3.27 percent), as did those with low systemic SS activity (OR 1.62, CI 95 1.22-2.15) and those who received mRNA vaccines, according to a multivariate analysis (OR 1.57, CI 95 percent 1.12- 2.18). The risk of developing systemic AEs was also higher in women (OR 2.85, CI 95 percent 1.60-5.2346), White people (OR 1.73, CI 95 1.14-2.65), and those who received a deficient vaccination regimen (OR 1.78, CI 95 1.12-2.88 percent). In addition to 141 (11%) patients who reported a significant worsening/exacerbation of their pre-vaccination sicca symptoms as a result of post-vaccination SS flares, 15 (1.2%) patients (13 women, mean age at vaccination 41.9 years) reported active involvement in the glandular (n=8), articular (n=7), cutaneous (n=6), pulmonary (n=2), and peripheral nervous system (n=1) domains as post-vaccination systemic flare. All side effects and flares subsided within 1-3 weeks, with no lasting effects or deaths. In terms of vaccination efficacy, breakthrough SARS-CoV-2 infection was confirmed after vaccination in three (0.24 percent) patients, all of whom recovered completely, and positive anti-SARS-Cov-2 antibodies were detected in approximately 95 percent of vaccinated SjS patients, according to data available. Conclusions. SARS-CoV-2 vaccination in patients with primary SjS, like other vaccines with adequate response and no safety signals, raised no concerns about the vaccine's efficacy or safety.
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Objectives. To determine characteristics associated with a more severe COVID-19 outcome in people with Sjogren's disease (SJD). Methods. People with SJD and COVID-19 reported to two international registries (Sjogren Big Data Consortium and COVID-19 Global Rheumatology Alliance) from March 2020 to October 2021 were included. An ordinal COVID-19 severity scale was defined: (1) not hospitalized, (2) hospitalized with no ventilation, (3) hospitalized requiring non-invasive ventilation, (4) hospitalized requiring invasive ventilation, and (5) death. Odds ratios (OR) were estimated using a multivariable ordinal logistic regression model adjusted for age, sex, comorbidities and anti-rheumatic medications included as covariates. Results. A total of 898 people with SJD were included (825 (91.8%) women, mean age SARS-CoV-2 infection diagnosis: 55.5 years), including 652 patients with primary SJD and 246 with other associated systemic rheumatic diseases. 33.9% were hospitalized, 14.5% required ventilation, and 4.3% died. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.05), male sex (OR 1.81, 95% CI 1.10 to 2.92), two or more comorbidities (OR 2.99, 95% CI 1.92 to 4.67;vs none), baseline therapy with corticosteroids (OR 2.04, 95% CI 1.20 to 3.46), immunosuppressive agents (OR 2.09, 95% CI 1.30 to 3.38) and B-cell depleting agents (OR 5.38, 95% CI 2.77 to 10.47) were associated with worse outcomes (reference for all medications: hydroxychloroquine only). Conclusions. More severe COVID-19 outcomes in individuals with Sjogren's are largely driven by demographic factors and baseline comorbidities. Patients using immunosuppressants, especially rituximab, also experienced more severe outcomes.
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Background: Patients with autoimmune infammatory diseases (AID) have been prioritized for urgent vaccination to mitigate COVID-19 risk. However, few studies in the literature assessed the immunogenicity and safety of the COVID-19 vaccine in patients with AID. Objectives: In this context, the present study aims to evaluate the immunogenic-ity and safety of the vaccine against COVID-19 in patients with AID. 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 in AID, in the real-life, in Brazil. Immunogenicity and adverse events (AE) from a single center were assessed, after 2 doses of ChAdOx1 (Oxford/AstraZeneca), 8 weeks of interval, in patients with AID and healthy controls (HC). Inclusion criteria were age ≥ 18 years and fulflling criteria according to international classifcation for AID. Exclusion criteria: pregnancy, previous severe AE to any vaccine, other immunosuppression causes. Stratifcation of post-vaccination AE was performed using a diary, flled out daily and returned at the end of 28 days for each dose. Participants were followed up through blood collection for measurement of IgG antibodies against SARS-CoV-2 spike receptor-binding domain by chemiluminescence (SARS-CoV-2 IgG II Quant assay, Abbott Laboratories, Abbott Park, IL, USA) at baseline and 28 days after the second dose. The seropositivity was defned for titers ≥50 AU/mL. Quantitative analyses were presented as observed frequency, percentage, central tendency, and variability measurements. The sample's normal distribution was verifed through the Shapiro-Wilk test. The Kruskal-Wallis test and the post-hoc Dwass-Steel-Critchlow-Fligner pairwise comparisons test were used to compare the IgG-S titers between the groups through the evaluation period. Categorical data were addressed using the Fisheŕs exact or Chi-squared (χ2) test. An alpha level of 5% signifcance was used in all analyses. Results: A total of 377 volunteers with AID and 50 HC were included in the study. Patients with spondyloarthritis (N=64), systemic lupus erythematosus (N=63), rheumatoid arthritis (N=61), primary Sjögren's syndrome (N=61), vasculitis (N=31), systemic sclerosis (N=14), inflammatory myopathy (N=9), Crohńs disease (N=49), ulcerative colitis (N=11) and other systemics AID (N=12) were evaluated. Both groups had female predominance (73.5% vs. 74.0%, p=0.937) and were homogeneous for age (43.5 vs. 41.7,p=0.308). The seroconversion among those not reactive (IgG-S negative at baseline) (46 HC and 191 AID), 28 days after second dose was 97.1% for spondyloar-thritis (p=0.425), systemic lupus erythematosus 88.2% (0.006), rheumatoid arthritis 93.5% (0.158), primary Sjögren's syndrome 92.6% (0.133), systemic sclerosis or inflammatory myopathy 47.1% (0.001), inflammatory bowel disease 100% (0.999) and vasculitis 80% (0.006), while in healthy control was 100%. In comparison with HC, there was a statistically significant difference in IgG-S titles only in systemic sclerosis or inflammatory myopathy (1.694 AU/ml vs. 3.719 AU/ml;p=0.006). Both groups only presented mild AE. Pain at the injection (85.7% vs. 78.4%, p=0.239), headache (67.3% vs. 53.8, p=0.074) and fatigue (59.2% Vs. 46.2%, p=0.089) were more common in HC than AID. Overall, reactions like arthralgia (52.6 vs. 22.4%, p<0.001), hematoma (14.1 vs. 4.1%, p=0.05), cutaneous rash (9.5 vs. 0%, p=0.024) were more frequent in AID. Most participants related that they felt safer after receiving a COVID-19 vaccination, and 52.4% did not reported a worse patient global assessment (PGA) index. Conclusion: In conclusion, our data indicated that ChAdOx1 vaccine is safe and induced high titers and seroconversion rate in AID. More severe AID, such as vasculitis, systemic lupus erythematosous, and systemic sclerosis and myositis showed a lower seroconversion rate. Further analysis will explore the association between immunossupressant and reactivity, and booster dose.
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Background: The SARS-CoV-2 virus has caused a worldwide health crisis. Patients with infammatory arthritis are at higher risk of hospitalization and death by COVID-19 due to comorbidities or immunosuppressive treatments. Vaccination is one the most important strategies to control the pandemic. Objectives: To evaluate the incident cases of SARS-CoV-2 infection in a multi-centric cohort of infammatory arthritis in Brazil. Methods: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their frst bDMARD or tsDMARD (1). The present analysis is a retrospective evaluation of adult patients with infam-matory arthritis (rheumatoid arthritis-RA, spondylarthritis-SpA and psoriatic arthritis-PsA) that were alive since the beginning of the COVID-19 pandemics in Brazil in February 2020. We evaluated the incidence and severity of COVID-19 infection and the adherence to anti-SARS-CoV-2 vaccines schedules, up to January 2022. Results: A total of 300 patients were interviewed and 69 (23.0%) reported con-frmed anti-SARS-CoV infection and 5 (1.7%) had a second infection. Among known infected patients, 18.8% need hospitalization and oxygen support, 7.2% were admitted at ICU, and 5.8% died. After COVID-19 infection, 31.8% reported worsening of disease activity but only 6.1% had modifcation in medication due to disease activity. Distribution of cases followed the pattern of waves observed in Brazil (Figure 1). Regarding vaccination, 285 (95%) reported to have received at least one dose of any anti-SARS-CoV-2 vaccine: 43% received the frst with the adenovirus ChAdOx1 nCoV-19 (AstraZeneca) adenovirus vaccine, 32% received the Sinovac-CoronaVac inactivated vaccine, 22% received the BNT162b2 (Pfzer-BioNtech) mRNA vaccine and 3% received the BNT162b2 (Pfzer-BioNtech) adenovirus vaccine. Almost all (98.1%) of these patients had already received the second dose of vaccine and after the frst and second vaccine doses, 6% and 4% of patients, respectively, reported worsening of articular disease activity, while, after the third dose, no patient reported disease activity worsening. Conclusion: During the pandemics, patients with infammatory arthritis had a pattern of distribution of cases very similar to general population. Adherence to vaccination is high and well tolerated.
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Background: The role of chronic use of hydroxychloroquine (HCQ) in rheumatic disease (RD) patients during the SARS-CoV-2 pandemic is still subject of discussion. Objectives: To compare the occurrence of COVID-19 and its outcomes between RD patients on HCQ use with individuals from the same household not taking the drug during community viral transmission in an observational prospective multicenter study in Brazil. Methods: Participants were enrolled and monitored through 24-week (From March 29th to Sep 30th, 2020) regularly scheduled phone calls performed by trained medical professionals. Epidemiological and demographic data, as well as RD disease activity status and current treatment data, specific information about COVID-19, hospitalization, need for intensive care, and death was recorded in both groups and stored in the Research Electronic Data Capture (REDCap) database. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. The statistical analysis was performed using IBM-SPSS v.20.0 software. Group comparisons were made using the Man-Whitney, Chi-Square and Fisher Exact Test, as well as multivariate regression models adjusted to confounders. Survival curves were performed using Kaplan-Meier analysis. Results: A total of 10,427 participants mean age (SD) of 44.04 (14.98) years were enrolled, including 6004 (57.6%) rheumatic disease patients, of whom 70.8% had systemic lupus erythematosus (SLE), 6.7% rheumatoid arthritis (RA), 4% primary Sjögren's syndrome (pSS), 1.8% mixed connective tissue disease (DMTC), 1% systemic sclerosis (SSc) and others (15.9), including overlap syndromes. In total, 1,132 (10.8%) participants fulfilled criteria for COVID-19, being 6.7% RD patients and 4.1% controls (p=0.002). A recent influenza vaccination had a protective role (p<0.001). Moderate and severe COVID-19 included the need for hospitalization, intensive care, mechanical ventilation or death. Infection severity was not different between groups (p=0.391) (Table 1). After adjustments for multiple confounders, the main risk factors significantly associated with COVID-19 were higher education level (OR=1.29 95%CI 1.05-1.59), being healthcare professionals (OR=1.91;95%CI 1.45-2.53), presence of two comorbidities (OR=1.31;95%CI 1.01-1.66) and three or more comorbidities associated (OR=1.69;95%CI 1.23-2.32). Interestingly, age ≥=65 years (OR=0.20;95%CI 0.11-0.34) was negatively associated. Regarding RD, the risk factors associated with COVID-19 diagnosys were SLE (OR= 2.37;95%CI 1.92-293), SSc (OR=2.25;95%CI 1.05-4.83) and rituximab use (OR=1.92;95%CI 1.13-3.26). In addition, age ≥=65 years (OR=5.47;95%CI 1.7-19.4) and heart disease (OR=2.60;95%CI 1.06-6.38) were associated with hospitalization. Seven female RD patients died, six with SLE and one with pSS, and the presence of two or more comorbidities were associated with higher mortality rate. Conclusion: Chronic HCQ use did not prevent COVID-19 in RD compared to their household cohabitants. Health care profession, presence of comorbidities LES, SSc and rituximab were identified as main risk factors for COVID-19 and aging and heart disease as higher risk for hospitalization. Our data suggest these outcomes could be considered to manage them in clinical practice.
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Background: Mental health was widely affected during the new coronavirus pandemic. In addition, some measures adopted by most countries in order to contain the virus spread, such as isolation and social distancing, leading to the interruption of routine activities, including partial or complete interruption of face-to-face classes may be associated with increased stress, depression and anxiety among undergraduate medical students (1). From March to September, 2020, the Brazilian Society of Rheumatology carried out the Mario Pinotti II Project (MPII), a prospective, multicenter, observational cohort study designed to monitor the COVID-19 in patients with rheumatic disease on hydroxychloroquine, using periodic telephone calls performed by undergraduate medical students (2). Objectives: To compare the mental health status of medical students who were participating from the MPII with theirs colleagues not involved in this project. Methods: A web-based survey via google forms platform was developed by a panel composed of undergraduate medical students, rheumatologists, medical school professors, and a psychology professor. It included details on demographic and life habits data and domains regarding depression, anxiety and stress, using the DASS-21 (Depression, Anxiety & Stress Scale), Brazilian version. Data collection occurred from July 20th to August 31st, 2020. Statistical analysis was performed using the SPSS version 20.0. Univariate and multivariate linear regression analysis were performed to verify associations with the DASS-21, defined as dependent variable. A p-value < 0.05 was deemed as significant. This study was approved by the Institutional Research Ethics Committee. Results: A total of 684 undergraduate medical students were included in this study, of whom 228 as MPII volunteers (VG) and 456 as control group (CG). Median age was 23 years (IQ 21-24) and the CG was older than the VG (p<0.03). Most of them were white (68.8%) and women (63%). There were no significant differences regarding comorbidities, ethnicity, smoking status, alcohol intake and physical activity. Older age, male gender, participation of MPII study, absence of a worsening in sleep pattern during the pandemic and a lower number of prior comorbidities were associated with lower DASS21 scores, suggesting a better mental health (Table 1). Conclusion: Several aspects may be involved with mental health, including increased emotional maturity, gender and sleep pattern. Although with marginal independent association, medical students with participation in the MPII study had better mental health than their student colleagues not engaged with this research. Our data pointed out that voluntary participation in a research project which foresees interaction by telephone contact with rheumatic patients, professors, rheumatologists, and colleagues is associated with better mental health.
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OBJECTIVES: To evaluate the incidence of COVID-19 and its main outcomes in rheumatic disease (RD) patients on hydroxychloroquine (HCQ) compared to household cohabitants (HC). METHODS: This is a 24-week nationwide prospective multi-centre cohort with a control group without RD and not using HCQ. All participants were monitored through scheduled phone interviews performed by health professionals. Details regarding COVID-19 symptoms, and epidemiological, clinical, and demographic data were recorded on a specific web-based platform. COVID-19 was defined according to the Brazilian Ministry of Health criteria and classified as mild, moderate or severe. RESULTS: A total of 9,585 participants, 5,164 (53.9%) RD patients on HCQ and 4,421 (46.1%) HC were enrolled from March 29th, 2020 to September 30th, 2020, according to the eligibility criteria. COVID-19 confirmed cases were higher in RD patients than in cohabitants [728 (14.1%) vs. 427 (9.7%), p<0.001] in a 24-week follow-up. However, there was no significant difference regarding outcomes related to moderate/ severe COVID-19 (7.1% and 7.3%, respectively, p=0.896). After multiple adjustments, risk factors associated with hospitalisation were age over 65 (HR=4.5;95%CI 1.35-15.04, p=0.014) and cardiopathy (HR=2.57;95%CI 1.12-5.91, p=0.026). The final survival analysis demonstrated the probability of dying in 180 days after a COVID-19 diagnosis was significantly higher in patients over 65 years (HR=20.8;95%CI 4.5-96.1) and with 2 or more comorbidities (HR=10.8;95%CI 1.1-107.9 and HR=24.8;95%CI 2.5-249.3, p=0.006, respectively). CONCLUSIONS: Although RD patients have had a higher COVID-19 incidence than individuals from the same epidemiological background, the COVID-19 severity was related to traditional risk factors, particularly multiple comorbidities and age, and not to underlying RD and HCQ.