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Objectives: To compare the impact of COVID-19 on the clinical status and psychological distress of patients with immune-mediated rheumatic disease (IMRD) caused by SARS-CoV-2 infection with that of noninfected IMRD controls during a 6-month follow-up period., Methods: The ReumaCoV Brazil is a longitudinal study designed to follow IMRD patients for 6 months after COVID-19 (patients) compared with IMRD patients without COVID-19 (controls). Clinical data, disease activity measurements and current treatments regarding IMRD and COVID-19 outcomes were evaluated in all patients. Disease activity was assessed through validated tools at inclusion and at 3 and 6 months post-COVID-19. Fatigue, using FACIT-F (Functional Assessment of Chronic Illness Therapy) and psychological distress, using DASS 21 (Depression, Anxiety and Stress Scale - 21 Items), used to evaluated psychological distress, were evaluated at 6 months after COVID-19 in both groups. The significance level was set as p < 0.05, with a 95% confidence interval., Results: A total of 601 patients were evaluated-321 patients (IMRD COVID-19 + patients) and 280 controls (IMRD COVID-19- patients)-who were predominantly female with similar median ages. Disease activity assessment over a 6-month follow-up showed no significant difference between cases and controls. Although the mean activity scores did not differ significantly, some patients reported worsened disease activity post-COVID-19, particularly in rheumatoid arthritis (RA) (32.2%) and systemic lupus erythematosus (SLE) patients (23.3%). Post-COVID-19 worsening in RA patients correlated with medical global assessment (MGA) and CDAI scores, with a moderate to large effect size. Diabetes mellitus showed a positive association (OR = 7.15), while TNF inhibitors had a protective effect (OR = 0.51). Fatigue, depression, anxiety, and stress were significantly greater in patients than in controls. Worse disease activity post-COVID-19 correlated with worse FACIT-F and DASS-21 scores in RA patients. No significant associations were found between COVID-19 outcomes and post-COVID-19 disease activity, FACIT-F or DASS-21., Conclusions: Post-COVID-19 IMRD patients exhibited significant fatigue, depression, anxiety, and stress, which can be mistaken for disease activity, despite having similar disease activity scores. The variability in reports on IMRD flares and the potential triggering of SARS-CoV-2 for autoimmune manifestations underscore the need for detailed clinical assessment and a comprehensive approach to managing them., Competing Interests: Declarations. Ethical approval and consent to participate: This study was conducted in accordance with the ethical principles for research involving human subjects and was approved by Research Ethics Committee of Hospital das Clínicas, Universidade Federal de Pernambuco, under reference number 3.955.206, CAAE 30186820.2.1001.8807, as a coordinator center. All patients read and signed an informed consent form before being included in the study. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: SARS-CoV-2 infection has become a major international issue, not only from a medical point of view, but also social, economic and political. Most of the available information comes from the United States, Europe, and China, where the population and the socioeconomic status are very different from Latin American countries. This study evaluates the effect of regional socioeconomic characteristics on mortality due SARS-CoV-2 infection in patients with immune-mediated rheumatic diseases (IMRD) from Argentina, Mexico and Brazil., Methods: Data from three national registries, SAR-COVID (Argentina), CMR-COVID (Mexico) and ReumaCoV-Brasil (Brazil), were combined. Adult IMRD patients with SARS-CoV-2 infection were recruited. National data for each province/state, including population density, number of physicians per inhabitant, income, unemployment, GINI index, Municipal Human Development Index (MHDI), stringency index, vaccination rate and most frequent viral strains per period were assessed as risk factors for mortality due to COVID-19., Results: A total of 4744 patients were included, 2534 (53.4%) from SAR-COVID, 1166 (24.6%) from CMRCOVID and 1044 (22.0%) from ReumaCoV-Brasil. Mortality due to COVID-19 was 5.4%. In the multivariable analysis, higher number of physicians per 1000 inhabitants and being infected during the vaccination period of each country were associated with lower mortality. After adjustment for socioeconomic factors, there was no association with country of residence and mortality., Conclusion: These findings corroborate the complex interplay between socioeconomic factors, rheumatic disease activity, and regional disparities as determinants of death due to COVID-19 in Argentina, Brazil and Mexico. Thus, this research provides valuable insights for guiding public health policies and clinical practice in the ongoing fight against the COVID-19 pandemic., (© 2024. The Author(s).)

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune-mediated rheumatic disease (IMRD) patients are scarce. This study describes breakthrough COVID-19 occurring in IMRD patients participating in the SAFER-study, a Brazilian multicentric cohort evaluating the safety, effectiveness, and immunogenicity of SARS-CoV-2 vaccines in patients with autoimmune diseases. A descriptive analysis of the population and a binary logistic regression model were performed to evaluate the predictors of COVID-19-related hospitalization. A p -value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with a mean (SD) age of 40.23 (13.19) years. The patients received two (19%), three (70%), or four (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) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n = 112) was with BNT162b2 (40%) or ChAdOx1 (26%). The COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84; CI: 1.9-18.5; p = 0.002) and treatment with corticosteroids (OR: 2.94; CI: 1.02-8.49; p = 0.0043) were associated with higher odds of hospitalization, while increasing the number of vaccine doses was protective (OR: 0.37; CI: 0.15-0.9; p = 0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favor of booster vaccination in IMRD patients.

Background: Patients 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 associated comorbidities. However, few studies have assessed the safety of the COVID-19 vaccine in patients with RA., Objective: To evaluate the safety of vaccines against SARS-CoV-2 in patients with RA., Methods: This data are from the study "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. Adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 (Oxford/AstraZeneca) or CoronaVac (Sinovac/Butantan). Stratification of postvaccination AEs was performed using a diary, filled out daily and returned at the end of 28 days for each dose., Results: A total of 188 patients with RA were include, 90% female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed, mainly after the first dose. The most common AEs after the first dose were pain at the injection (46,7%), headache (39,4%), arthralgia (39,4%), myalgia (30,5%) and fatigue (26,6%), and ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0.001) arthralgia (62% vs 22%, p < 0.001) and myalgia (45% vs 20%, p < 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection (37%), arthralgia (31%), myalgia (23%), headache (21%) and fatigue (18%). Arthralgia (41,4% vs 25%, p = 0.02) and pain at injection (51,4% vs 27%, p = 0.001) were more common with ChAdOx1. No serious AEs were related. With Regard to RA activity level, no significant difference was observed between the three time periods for both COVID-19 vaccines., Conclusion: In the comparison between the two immunizers in patients with RA, local reactions and musculoskeletal symptoms were more frequent with ChAdOx1 than with CoronaVac, especially after the first dose. In summary, the AE occurred mainly after the first dose, and were mild, like previous data from others immunizing agents in patients with rheumatoid arthritis. Vaccination did not worsen the degree of disease activity., (© 2024. The Author(s).)

Objective: To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide., Materials and Methods: The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators., Results: Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered., Conclusion: The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases., (© 2024. The Author(s).)

Objectives: To evaluate the disease activity before and after COVID-19 and risk factors associated with outcomes, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV) and death in patients with spondylarthritis (SpA)., Methods: ReumaCoV Brazil is a multicenter prospective cohort of immune-mediated rheumatic diseases (IMRD) patients with COVID-19 (case group), compared to a control group of IMRD patients without COVID-19. SpA patients enrolled were grouped as axial SpA (axSpA), psoriatic arthritis (PsA) and enteropathic arthritis, according to usual classification criteria., Results: 353 SpA patients were included, of whom 229 (64.9%) were axSpA, 118 (33.4%) PsA and 6 enteropathic arthritis (1.7%). No significant difference was observed in disease activity before the study inclusion comparing cases and controls, as well no worsening of disease activity after COVID-19. The risk factors associated with hospitalization were age over 60 years (OR = 3.71; 95% CI 1.62-8.47, p = 0.001); one or more comorbidities (OR = 2.28; 95% CI 1.02-5.08, p = 0.001) and leflunomide treatment (OR = 4.46; 95% CI 1.33-24.9, p = 0.008). Not having comorbidities (OR = 0.11; 95% CI 0.02-0.50, p = 0.001) played a protective role for hospitalization. In multivariate analysis, leflunomide treatment (OR = 8.69; CI = 95% 1.41-53.64; p = 0.023) was associated with hospitalization; teleconsultation (OR = 0.14; CI = 95% 0.03-0.71; p = 0.01) and no comorbidities (OR = 0.14; CI = 95% 0.02-0.76; p = 0.02) remained at final model as protective factor., Conclusions: Our results showed no association between pre-COVID disease activity or that SARS-CoV-2 infection could trigger disease activity in patients with SpA. Teleconsultation and no comorbidities were associated with a lower hospitalization risk. Leflunomide remained significantly associated with higher risk of hospitalization after multiple adjustments., (© 2022. The Author(s).)

Background: Patients using immunosuppressive drugs may have unfavorable results after infections. However, there is a lack of information regarding COVID-19 in these patients, especially in patients with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the risk factors associated with COVID-19 hospitalizations in patients with RA., Methods: This multicenter, prospective cohort study is within the ReumaCoV Brazil registry and included 489 patients with RA. In this context, 269 patients who tested positive for COVID-19 were compared to 220 patients who tested negative for COVID-19 (control group). All patient data were collected from the Research Electronic Data Capture database., Results: The participants were predominantly female (90.6%) with a mean age of 53 ± 12 years. Of the patients with COVID-19, 54 (20.1%) required hospitalization. After multiple adjustments, the final regression model showed that heart disease (OR = 4.61, 95% CI 1.06-20.02. P < 0.001) and current use of glucocorticoids (OR = 20.66, 95% CI 3.09-138. P < 0.002) were the risk factors associated with hospitalization. In addition, anosmia was associated with a lower chance of hospitalization (OR = 0.26; 95% CI 0.10-0.67, P < 0.005)., Conclusion: Our results demonstrated that heart disease and the use of glucocorticoids were associated with a higher number of hospital admissions for COVID-19 in patients with RA., Trial Registration: Brazilian Registry of Clinical Trials - RBR-33YTQC., (© 2022. The Author(s).)

Objective: To provide guidelines on the coronavirus disease 2019 (COVID-19) vaccination in patients with immune-mediated rheumatic diseases (IMRD) to rheumatologists considering specific scenarios of the daily practice based on the shared-making decision (SMD) process., Methods: A task force was constituted by 24 rheumatologists (panel members), with clinical and research expertise in immunizations and infectious diseases in immunocompromised patients, endorsed by the Brazilian Society of Rheumatology (BSR), to develop guidelines for COVID-19 vaccination in patients with IMRD. A consensus was built through the Delphi method and involved four rounds of anonymous voting, where five options were used to determine the level of agreement (LOA), based on the Likert Scale: (1) strongly disagree; (2) disagree, (3) neither agree nor disagree (neutral); (4) agree; and (5) strongly agree. Nineteen questions were addressed and discussed via teleconference to formulate the answers. In order to identify the relevant data on COVID-19 vaccines, a search with standardized descriptors and synonyms was performed on September 10th, 2021, of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and LILACS to identify studies of interest. We used the Newcastle-Ottawa Scale to assess the quality of nonrandomized studies., Results: All the nineteen questions-answers (Q&A) were approved by the BSR Task Force with more than 80% of panelists voting options 4-agree-and 5-strongly agree-, and a consensus was reached. These Guidelines were focused in SMD on the most appropriate timing for IMRD patients to get vaccinated to reach the adequate covid-19 vaccination response., Conclusion: These guidelines were developed by a BSR Task Force with a high LOA among panelists, based on the literature review of published studies and expert opinion for COVID-19 vaccination in IMRD patients. Noteworthy, in the pandemic period, up to the time of the review and the consensus process for this document, high-quality evidence was scarce. Thus, it is not a substitute for clinical judgment., (© 2022. The Author(s).)

Background: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil., Methods: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19., Results: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren's syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98)., Conclusion: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6)., (© 2021. The Author(s).)

Background: The COVID-19 pandemic has resulted in social isolation, which has a potential negative impact on the educational routines (eg, the suspension of face-to-face appointments) and mental health of medical students. The Mario Pinotti II (MPII) study is a 24-week observational study that conducted scheduled telephone calls every 2 weeks to verify the occurrence of COVID-19 in patients with rheumatic diseases on chronic hydroxychloroquine therapy (from March 29, 2020, to September 30, 2020). The effects of voluntarily participating in a research project (ie, one that involves interactions via telephone contact with patients, professors, rheumatologists, and colleagues) on the daily lives and mental health of medical students requires evaluation., Objective: As medical students are professionals in training and have a high level of responsibility in terms of handling the emotional and physical aspects of several diseases, this study aims to evaluate the impacts of the COVID-19 pandemic and participation in the MPII study on the educational routines and mental health of medical students., Methods: A web-based survey was carried out to perform a cross-sectional comparative assessment of medical students who participated in the MPII study and their colleagues who were not involved in the MPII study. Participants from both groups were matched based on sex, age, and medical school. The web questionnaire was developed by a panel composed of graduate medical students, rheumatologists, medical school professors, and a psychology professor. The questionnaire included details on demographic and life habits data and evaluated participants' impressions of the MPII study and the impact of the COVID-19 pandemic on their educational routines and medical training. In addition, depression, anxiety, and stress were evaluated using the Brazilian version of the Depression, Anxiety, and Stress Scale (DASS)-21, and currently, the DASS-21 scores are grouped as those that indicate a low, moderate, or high risk of mental distress. This project was approved by the Federal University of São Paulo Ethics Committee (CAAE: 34034620.0.0000.5505)., Results: Data were collected from both medical student groups from July 20 to August 31, 2020. Data extraction was completed in September 2020. The data analysis is ongoing. We expect the results to be published in the first semester of 2021., Conclusions: This study will provide insight into the effects of participating in a research project on depression, anxiety, and stress, which will be determined by applying the DASS-21 to a large sample of Brazilian undergraduate medical students. We will also evaluate the impact of the COVID-19 pandemic on medical students' educational routines and medical training., International Registered Report Identifier (irrid): DERR1-10.2196/24617., (©Débora Cerqueira Calderaro, Barbara Stadler Kahlow, Gabriela Araújo Munhoz, Samuel Elias Basualto Dias, João Vitor Ziroldo Lopes, Aline Rizzo Borges, Henrique De Ataíde Mariz, Kirla Wagner Poti Gomes, Lilian David De Azevedo Valadares, Nafice Costa Araújo, Sandra Lucia Euzébio Ribeiro, Adriana Maria Kakehasi, Ana Paula Monteiro Gomides Reis, Cláudia Marques, Edgard Torres Reis-Neto, Eduardo Dos Santos Paiva, Gecilmara Salviato Pileggi, Gilda Aparecida Ferreira, José Roberto Provenza, Licia Maria Henrique Mota, Ricardo Machado Xavier, Maycoln Leôni Martins Teodoro, Marcelo De Medeiros Pinheiro, The Voluntary Brazilian Society Of Rheumatology Task Force Against COVID-19. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.04.2021.)

Objectives: To evaluate risk factors associated with unfavourable outcomes: emergency care, hospitalisation, admission to intensive care unit (ICU), mechanical ventilation and death in patients with immune-mediated rheumatic disease (IMRD) and COVID-19., Methods: Analysis of the first 8 weeks of observational multicentre prospective cohort study (ReumaCoV Brasil register). Patients with IMRD and COVID-19 according to the Ministry of Health criteria were classified as eligible for the study., Results: 334 participants were enrolled, a majority of them women, with a median age of 45 years; systemic lupus erythematosus (32.9%) was the most frequent IMRD. Emergency care was required in 160 patients, 33.0% were hospitalised, 15.0% were admitted to the ICU and 10.5% underwent mechanical ventilation; 28 patients (8.4%) died. In the multivariate adjustment model for emergency care, diabetes (prevalence ratio, PR 1.38; 95% CI 1.11 to 1.73; p=0.004), kidney disease (PR 1.36; 95% CI 1.05 to 1.77; p=0.020), oral glucocorticoids (GC) (PR 1.49; 95% CI 1.21 to 1.85; p<0.001) and pulse therapy with methylprednisolone (PR 1.38; 95% CI 1.14 to 1.67; p=0.001) remained significant; for hospitalisation, age >50 years (PR 1.89; 95% CI 1.26 to 2.85; p=0.002), no use of tumour necrosis factor inhibitor (TNFi) (PR 2.51;95% CI 1.16 to 5.45; p=0.004) and methylprednisolone pulse therapy (PR 2.50; 95% CI 1.59 to 3.92; p<0.001); for ICU admission, oral GC (PR 2.24; 95% CI 1.36 to 3.71; p<0.001) and pulse therapy with methylprednisolone (PR 1.65; 95% CI 1.00 to 2.68; p<0.043); the two variables associated with death were pulse therapy with methylprednisolone or cyclophosphamide (PR 2.86; 95% CI 1.59 to 5.14; p<0.018)., Conclusions: Age >50 years and immunosuppression with GC and cyclophosphamide were associated with unfavourable outcomes of COVID-19. Treatment with TNFi may have been protective, perhaps leading to the COVID-19 inflammatory process., Competing Interests: Competing interests: CDLM reports grants from National Council for Scientific and Technological Development (CNPq) and from Brazilian Society of Rheumatology, personal fees from Janssen, Novartis, Abbvie. AMK reports personal fees from Abbvie, Janssen, Pfizer, Lilly and Roche. MMP reports personal fees from Abbvie, Janssen, UCB, Novartis, Pfizer and Lilly. LMHM reports personal fees from Abbvie, Janssen, Pfizer, Roche, Boehringer Ingelheim, GSK, Libbs and Lilly. CRS reports personal fees from Pfizer, Abbvie and Novartis. AD reports personal fees from Boehringer Ingelheim. RDG reports personal fees from Janssen, Eli Lilly, Roche, Boehringer Ingelheim, Amgen Brasil, Pfizer, Sandoz, Novartis Brasil. LDAV personal fees from Janssen, Novartis and UCB. AKGM reports grants from Brazilian Society of Rheumatology, personal fees from Janssen and UCB. MAY reports personal fees from Novartis, Abbvie, Lilly and, UCB. RAdT reports personal fees from ABBVIE, GSK, JANSSEN, NOVARTIS, LILLY, PFIZER, ROCHE and UCB. RX reports grants and personal fees from Abbvie, Eli-Lilly, Pfizer, Janssen and Roche, personal fees from Novartis, UCB., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with immune-mediated rheumatic diseases (IMRD) are at increased risk of infections, including significant morbidity and high mortality. Considering the potential for unfavorable outcomes of SARS-CoV-2 infection in patients with IMRD, several questions were raised regarding the impact of COVID-19 at the start of the pandemic., Objective: This paper presents the protocol of a study that aims to prospectively evaluate patients with IMRD and a confirmed COVID-19 diagnosis (using criteria provided by the Brazilian Ministry of Health)., Methods: The study comprised a prospective, observational cohort (patients with IMRD and COVID-19) and a comparison group (patients with only IMRD), with a follow-up time of 6 months to evaluate differences in health outcomes. The primary outcomes will be changes in IMRD disease activity after SARS-CoV-2 infection at 4 time points: (1) at baseline, (2) within 4-6 weeks after infection, (3) at 3 months after the second assessment (±15 days), and (4) at 6 months (±15 days). The secondary outcomes will be the progression rate to moderate or severe forms of COVID-19, need for intensive care unit admission and mechanical ventilation, death, and therapeutic changes related to IMRD. Two outcomes-pulmonary and thromboembolic events in patients with both IMRD and SARS-CoV-2 infection-are of particular interest and will be monitored with close attention (clinical, laboratory, and function tests as well as imaging)., Results: Recruitment opened in May 2020, with 1300 participants recruited from 43 sites as of November 2020. Patient recruitment will conclude by the end of December 2020, with follow-up occurring until April 2021. Data analysis is scheduled to start after all inclusion data have been collected, with an aim to publish a peer-reviewed paper in December 2020., Conclusions: We believe this study will provide clinically relevant data on the general impact of COVID-19 on patients with IMRD., Trial Registration: Brazilian Registry of Clinical Trials RBR-33YTQC; http://www.ensaiosclinicos.gov.br/rg/RBR-33ytqc/., International Registered Report Identifier (irrid): DERR1-10.2196/24357., (©Claudia Marques, Adriana Maria Kakehasi, Ana Paula Monteiro Gomides, Eduardo Dos Santos Paiva, Edgard Torres dos Reis Neto, Gecilmara Cristina Salviato Pileggi, José Roberto Provenza, Licia Mota, Ricardo Machado Xavier, Gilda Aparecida Ferreira, Marcelo Medeiros Pinheiro. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 15.12.2020.)

Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.

Objective: To determine the incidence of positive CMV antigenemia (CMV-Ag) in patients with autoimmune rheumatic diseases (AIRD) and to describe the outcomes of these patients., Methods: From January 2011 to December 2014, a total of 443 patients with AIRD were enrolled in this retrospective analysis. Demographic, clinical and laboratory data, current clinical manifestations, organs affected by CMV infection, therapeutic management and outcomes were evaluated. The CMV-Ag was considered positive when one cell was detected at least., Results: CMV-Ag was requested in 70 (15.8%) patients with suspicious CMV infection and was positive in 24 (34.3%). The incidence rate of positive CMV-Ag was 4.97% (95% CI 3.1-7.4%). Systemic lupus erythematosus (SLE) (59%), followed by ANCA-related vasculitis (18.2%) and rheumatoid arthritis (9%) were the diseases more associated with positive CMV-Ag. At the time of CMV infection, SLE patients had moderate to severe disease activity, with high frequency of positive anti-dsDNA antibody (69.2%) and complement consumption (61.5%), as well as high doses of corticosteroids and use of immunosuppressants. The main CMV sites involved were lung (45.5%), bone marrow (40.9%) and gut (27.3%). Mortality rate was 45.5%, especially in those with higher doses of daily oral corticosteroids (107 ± 55.4 mg vs. 71.7 ± 46.3 mg; p = 0.07) and lower number of lymphocytes (309 ± 368.2/mm 3 vs. 821 ± 692.9/mm 3 ; p = 0.06)., Conclusions: Our data showed high incidence of CMV-Ag in AIRD patients, particularly those with SLE and greater disease severity. In addition, it was observed high mortality in these patients, highlighting the CMV infection should be included in differential diagnosis.

Objectives: To evaluate the impact and risk factors associated with an abnormal exercise test (ET) in systemic inflammatory rheumatic disease (SIRD) patients before commencing supervised physical exercise., Methods: A total of 235 SIRD patients were enrolled in three controlled clinical trials, including 103 RA, 42 SLE and 57 AS patients. The control group consisted of 231 healthy, sedentary subjects matched for age, gender and BMI. All performed an ET, according to Bruce's or Ellestad's protocol. Cardiovascular disease risk factors, medications, comorbidities and details of each SIRD were assessed., Results: SIRD patients had a higher percentage of abnormal ETs compared with the control group, especially exercise hypertensive behaviour, higher oxygen consumption, higher resting heart rate and heart rate at the first minute of recovery, and chronotropic incompetence (C-Inc) (P < 0.001). The disease itself was involved with higher likelihood of having an abnormal ET [Odds ratio (OR) = 12.0, 95% CI: 2.5, 56.7; P = 0.002 for SLE; OR = 13.56, 95% CI: 6.16, 29.8; P < 0.001 for RA; and OR = 4.31, 95% CI: 1.17, 15.8; P = 0.028, for AS]. Each 10-year increment of age increased the chance of having an abnormal ET by 13% (P = 0.008) in AS patients, as well as hypertension (OR = 7.14, 95% CI: 1.61, 31.6; P = 0.01). Regarding C-Inc, age played a protective role (OR = 0.88, 95% CI: 0.78, 0.99; P = 0.043) in SLE, and ASDAS-ESR was associated with a higher risk in AS (OR = 2.73, 95% CI: 0.93, 8.0; P = 0.067)., Conclusion: Our results showed a higher prevalence of abnormal ETs in asymptomatic cardiovascular SIRD patients, and the disease itself was associated with a higher likelihood of having an abnormal test, emphasizing the relevance and need of performing it before starting supervised physical exercise., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: The objective of this study was to evaluate the effect of supervised physical exercise on endothelial function, ergospirometric test variables and disease activity in SLE patients., Methods: We conducted a prospective study in which women with SLE who were available to perform physical exercise were allocated to the exercise group (EG) to practise supervised physical exercise for 1 h three times per week for 16 weeks. Those who were not available for this activity were allocated to the control group (CG). Intervention consisted of walking at a heart rate corresponding to the ventilatory 1 threshold obtained from ergospirometry and monitored by a frequency meter. At baseline (T0) and after 16 weeks (T16), patients were assessed for endothelial function by brachial artery (flow-mediated dilation), ergospirometry and disease activity (SLEDAI). Statistical analysis was performed through normality tests, Student's t-test and non-parametric tests for data with non-normal distribution. P < 0.05 was considered significant., Results: Eighteen patients were allocated in the EG and 20 in the CG. After 16 weeks there was an increase in FMD in the EG [6.3 (6.7)% vs 14.1 (9.1)%, P = 0.006] without a change in the CG [8.4 (8.2)% vs 9.4 (5.7)%, P = 0.598]. Regarding the ergospirometric test, we found improvement in exercise tolerance [12.3 (2.4) vs 13.4 (2.6) min, P = 0.027], maximum speed [7.7 (1.0) vs 8.3 (1.2) km/h, P = 0.027] and threshold speed [5.6 (0.7) vs 6.1 (0.9) km/h, P = 0.005] in the EG without a difference in the CG. There was no difference in the SLEDAI score in both groups., Conclusion: Physical exercise is a useful strategy to improve endothelial function and aerobic capacity without worsening disease activity in SLE patients. TRIAL REGISTRATION; ClinicalTrials.gov (http://www.clinicaltrials.gov), NCT01712529.

Objective: We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-α therapy., Methods: A total of 257 patients with active arthritis who were taking TNF-α blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05., Results: After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years) were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%), parasitic (23.5%), fungal (20.6%) and viral (8.8%) agents., Conclusion: The skin is significantly affected by adverse reactions resulting from the use of TNF-α blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab.

Objectives: To assess clinical response after switching between anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents in patients with rheumatoid arthritis (RA)., Patients and Methods: This study included 99 patients diagnosed with RA American College of Rheumatology, 1987), on anti-TNF-alpha therapy, to assess the therapeutic response after 24 weeks. Switching was performed if, after 12 to 24 weeks, a severe adverse event was reported (toxicity: T) or if no reduction greater than 0.6 in the initial Disease Activity Score 28 (DAS28) occurred (inadequate response: IR). In case of IR, the patient was considered as primary failure (PF). Secondary failure (SF) was defined as loss of response after initial improvement. Remission (DAS28 < 2.6), low disease activity (between 2.61 and 3.2), and functional improvement [increase in the initial Health Assessment Questionnaire (HAQ) > 0.2] were assessed by use of linear regression analysis. The significance level adopted was P < 0.05., Results: Switching was performed in 39 (39.4%) patients, especially due to PF (24.3%), SF (35.1%) and T (40.5%). The retention rate of the first agent was 60.1%, and the mean time for switching was 14.2 ± 10.9 months. After switching, a tendency towards a decrease in DAS28 was observed (4.7 ± 1.4; P = 0.08), but not in the HAQ (1.2 ± 0.77; P = 0.11). Around 43% of the patients achieved good/moderate EULAR response. The major determinant of switching was a higher initial DAS28, independent of age, duration of disease, and functional capacity., Conclusion: Switching between anti-TNF-alpha agents is a valid strategy to control disease activity, despite the low likelihood of remission and no significant improvement in functional capacity.

Objective: To estimate the prevalence and analyze risk factors associated to osteoporosis and low-trauma fracture in women., Methods: Cross-sectional study including a total of 4,332 women older than 40 attending primary care services in the Greater São Paulo, Southeastern Brazil, between 2004 and 2007. Anthropometrical and gynecological data and information about lifestyle habits, previous fracture, medical history, food intake and physical activity were obtained through individual quantitative interviews. Low-trauma fracture was defined as that resulting from a fall from standing height or less in individuals 50 years or older. Multiple logistic regression models were designed having osteoporotic fracture and bone mineral density (BMD) as the dependent variables and all other parameters as the independent ones. The significance level was set at p<0.05., Results: The prevalence of osteoporosis and osteoporotic fractures was 33% and 11.5%, respectively. The main risk factors associated with low bone mass were age (OR=1.07; 95% CI: 1.06;1.08), time since menopause (OR=2.16; 95% CI: 1.49;3.14), previous fracture (OR=2.62; 95% CI: 2.08;3.29) and current smoking (OR=1.45; 95% CI: 1.13;1.85). BMI (OR=0.88; 95% CI: 0.86;0.89), regular physical activity (OR=0.78; 95% CI: 0.65;0.94) and hormone replacement therapy (OR=0.43; 95% CI: 0.33;0.56) had a protective effect on bone mass. Risk factors significantly associated with osteoporotic fractures were age (OR=1.05; 95% CI: 1.04;1.06), time since menopause (OR=4.12; 95% CI: 1.79;9.48), familial history of hip fracture (OR=3.59; 95% CI: 2.88;4.47) and low BMD (OR=2.28; 95% CI: 1.85;2.82)., Conclusions: Advanced age, menopause, low-trauma fracture and current smoking are major risk factors associated with low BMD and osteoporotic fracture. The clinical use of these parameters to identify women at higher risk for fractures might be a reasonable strategy to improve the management of osteoporosis.

Background: Vessel wall inflammation, atherosclerosis and hypercoagulability may be responsible for ischemic events in Takayasu arteritis (TA). No study has evaluated the effect of antiplatelet therapy for the prevention of ischemic events in TA., Methods and Results: Forty-eight patients who met the ACR Classification Criteria for TA under follow-up at the Vasculitis Unit of Universidade Federal de São Paulo were evaluated retrospectively for clinical manifestations, therapy and arterial ischemic events. The mean age at study was 38.0 years and the mean age at TA diagnosis was 29.1 years. Women comprised for 89.6% of patients and 60.4% were Caucasian. Risk factors for cardiovascular disease were found in 44 patients (91.7%) The most common comorbidities for TA patients were hypertension (77.1%), high low-density lipoprotein (45.8%) and obesity (16.7%). Antiplatelet therapy was used by 62.5% of patients whereas anticoagulants were used by 12.5%. Acute ischemic events occurred in 29.2% of patients. TA patients with ischemic events used significantly less antiplatelet agents (14.3%) than those without ischemic events (82.4%), P<0.0001. No difference concerning ischemic events was observed in patients on anticoagulant therapy (P=0.339). The 3 deaths of TA patients were observed only in those who had presented ischemic events (P=0.021). Antiplatelet agents had a protective effect against ischemic events (hazard ratio =0.055, 95% confidence interval: 0.06-0.514; P=0.011)., Conclusions: Antiplatelet therapy is associated with a lower frequency of ischemic events in patients with TA.

TNF blockers have been used in the treatment of several types of chronic inflammatory arthritis, especially rheumatoid arthritis. However, many doubts regarding the safety and high risk of infectious diseases in these patients remain. The main objective of this report was to present a case of lepromatous leprosy in a rheumatoid arthritis patient using TNF blockers. The development of adverse events should be rigorously observed, especially those related to infectious agents. Thus, appropriate investigation of skin lesions in patients receiving anti-TNFα therapy is recommended, as the initial clinical manifestation may be unusual, particularly in endemic regions in Brazil.