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Objectives To assess immunogenicity of a heterologous fourth dose of an mRNA (BNT162b2) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in autoimmune rheumatic diseases (ARD) patients with poor/non-response to inactivated vaccine (Sinovac-CoronaVac). Methods A total of 164 ARD patients who were coronavirus disease 2019 (COVID-19) poor/non-responders (negative anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies—NAb) to the third dose of Sinovac-CoronaVac received an additional heterologous dose of mRNA (BNT162b2) 3 months after last dose. IgG and NAb were evaluated before and after the fourth dose. Results Significant increases were observed after the fourth dose in IgG (66.4 vs 95.1%, P Conclusions This is the largest study to provide evidence of a remarkable humoral response after the fourth dose of heterologous mRNA SARS-CoV-2 vaccination in ARD patients with poor/non-response to the third dose of an inactivated vaccine. We further identified that treatment, particularly rituximab and prednisone, impaired antibody response to this additional dose. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, CoronavRheum #NCT04754698.

To date, the only study that has assessed the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 mRNA) vaccine in systemic lupus erythematosus (SLE) observed a moderate response, but the sample size precluded an accurate analysis of the effect of individual drugs. Therefore, we evaluated the immunogenicity of an inactivated SARS-CoV-2 vaccine (Sinovac-CoronaVac) and the influence of different medications in SLE. Safety was also assessed.We conducted a prospective controlled study of 232 SARS-CoV-2-naive SLE patients and 58 SARS-CoV-2-naive controls who were vaccinated with 2 doses of Sinovac-CoronaVac with a 28-day interval (day 0/day 28 [D0/D28]). Immunogenicity analysis at D0/D28 and D69 included anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralizing antibodies (NAb) positivity. The influence of individual drugs on immune response and safety was assessed.Patients and controls were well balanced for age (P = 0.771). At D69, SLE patients showed a moderate SC (70.2% versus 98.1%; P 0.001) and moderate frequency of NAb positivity (61.5% versus 84.6%; P = 0.002), although both frequencies were lower than in controls. Factors associated with lower SC in univariate analysis at D69 were prednisone use (odds ratio [OR] 0.215 [95% confidence interval (95% CI) 0.108-0.427], P 0.001) and mycophenolate mofetil (MMF) use (OR 0.201 [95% CI 0.107-0.378], P 0.001), whereas hydroxychloroquine (HCQ) use led to a 2.5 increase in SC (P = 0.011). SLE patients who were receiving HCQ monotherapy had similar SC to controls at D69 (100% versus 98.1%; P = 1.000). In multivariate analysis, prednisone and MMF use were independently associated with lower SC (P 0.001) and NAb positivity (P 0.001). Safety analysis revealed no moderate/severe adverse events.Sinovac-CoronaVac has a moderate immunogenicity in SARS-CoV-2-naive SLE patients with an excellent safety profile. We further demonstrate that HCQ may improve SC, whereas prednisone and MMF had a major deleterious effect in vaccine response, reinforcing the need to investigate the role of temporary MMF withdrawal or a vaccine-booster dose (ClinicalTrials.gov identifier: NCT04754698).

This randomized controlled study aimed to investigate whether a single bout of exercise before the homologous booster dose of a SARS-CoV-2 inactivated vaccine could enhance immunogenicity in patients with spondyloarthritis. We selected 60 consecutive patients with spondyloarthritis (SpA). Patients assigned to the intervention group performed an exercise bout comprising three exercises. Then, they remained at rest for 1 h before vaccination. The control group remained at rest before vaccination. Immunogenicity was assessed before (Pre) and 1 mo after (Post) the booster using seropositivity rates of total anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG (GMT), frequency of neutralizing antibodies (NAb) positivity, and NAb activity. At Pre, 16 patients from the exercise group and 16 patients from the control group exhibited seropositivity for IgG (59% vs. 57.1%), and 1 mo after the booster dose, seropositivity occurred in 96% versus 100% of the cases. Only 10 patients from the exercise group and 12 patients from the control group showed positive NAb serology at Pre (37% vs. 42.8%). One month following the booster, NAb positivity was 96% versus 93%. GMT was comparable between groups at Pre. At Post, GMT increased similarly in both groups. Likewise, NAb activity was similar between groups at Pre and increased similarly in both of them as a result of the booster (47.5% vs. 39.9%). In conclusion, a single bout of exercise did not enhance immunogenicity to a homologous booster dose of an inactivated SARS-CoV-2 vaccine among patients with spondyloarthritis.

Objectives To investigate whether physical activity is associated with enhanced immunogenicity of a SARS-CoV-2 inactivated vaccine (Coronavac) in patients with autoimmune rheumatic diseases (ARD) (n = 898) and in non-ARD (n = 197) individuals without pre-existing immunogenicity to SARS-CoV-2. Methods This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial. Immunogenicity was assessed after vaccination by measuring seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG (SC), geometric mean titers of anti-S1/S2 IgG (GMT), factor-increase in GMT (FI-GMT), frequency of neutralizing antibody (NAb), and median neutralizing activity. Physical activity (active being defined as ≥ 150 min/week) and sedentary behavior (>8h/day) were assessed by questionnaire. Results Physically active ARD patients (n = 494) were younger and less frequently used prednisone/biologics than inactive patients (n = 404). After controlling for covariates, active patients exhibited greater SC (OR: 1.4 [95%CI: 1.1–2.0]), GMT (32% [95%CI: 8.8–60) and FI-GMT (33% [95%CI: 9.6–63%]) vs. inactive. Cluster analysis (physical activity/sedentary status) revealed greater GMT (43.0% [95% CI: 11.0–84.0%) and FI-GMT (48.0% [95%CI: 14.0–92.0%]) in active/non-sedentary vs. inactive/sedentary ARD patients. A dose–response was observed, with greater benefits for the group of patients performing ≥ 350 min/week of physical activity (OR: 1.6 [95%CI: 1.1–2.4]; 41% [95%CI: 10–80%]; 35% [95%CI: 4.3–74], for SC, GMT, and FI-GMT, respectively) vs. the least active group (≤30 min/week). Greater SC (OR: 9.9 [95%CI: 1.1–89.0]) and GMT (26% [95%CI: 2.2–56.0%]) were observed in active vs. inactive non-ARD. Conclusions A physically active lifestyle may enhance SARS-CoV-2 vaccine immunogenicity, a finding of particular clinical relevance for immunocompromised patients. Trial Registration Clinicaltrials.gov #NCT04754698.

Background We aimed to examine the immunogenicity pattern induced by the inactivated SARS-CoV-2 vaccine CoronaVac (Sinovac Life Sciences, Beijing, China) in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases compared with seropositive controls, seronegative patients with autoimmune rheumatic diseases, and seronegative controls. Methods CoronavRheum is an ongoing, prospective, controlled, phase 4 study, in which patients aged 18 years or older with autoimmune rheumatic diseases, and healthy controls were recruited from a single site (Rheumatology Division of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo) in São Paulo, Brazil Participants were vaccinated with two doses of CoronaVac (intramuscular injection, 3 μg in 0·5 mL of β-propiolactone inactivated SARS-CoV-2) on day 0 and on day 28. Blood samples were taken pre-vaccination on day 0, day 28, and also on day 69. For this subgroup analysis, participants were defined as being SARS-CoV-2 seropositive or seronegative prevaccination via anti-SARS-CoV-2 spike (S)1 or S2 IgG (cutoff of 15·0 arbitrary units [AU] per mL) or neutralising antibody titres (cutoff of ≥30%) and were matched for age and sex, via convenience sampling, in a 1:3:1:1 ratio (seropositive patients to seronegative patients to seropositive controls to seronegative controls). The primary outcomes were rates of anti-SARS-CoV-2 S1 and S2 IgG seropositivity and SARS-CoV-2 neutralising antibody positivity at day 28 and day 69 and immunogenicity dynamics assessed by geometric mean titres (GMTs) of IgG and median neutralising activity in seropositive patients with autoimmune rheumatic diseases compared with seronegative patients and seropositive and seronegative controls. We assessed safety in all participants randomly selected for this subgroup analysis. This study is registered with ClinicalTrials.gov, NCT04754698, and is ongoing for long-term immunogenicity evaluation. Findings Between Feb 4 and Feb 8, 2021, 1418 patients and 542 controls were recruited, of whom 1685 received two vaccinations (1193 patients and 492 controls). After random sampling, our immunogenicity analysis population comprised 942 participants, of whom 157 were SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases, 157 were seropositive controls, 471 were seronegative patients, and 157 were seronegative controls; the median age was 48 years (IQR 38–56) and 594 (63%) were female and 348 (37%) were male. For seropositive patients and controls, an increase in anti-SARS-CoV-2 S1 and S2 IgG titres (seropositive patients GMT 52·3 [95% CI 42·9–63·9] at day 0 vs 128·9 [105·6–157·4] at day 28; seropositive controls 53·3 [45·4–62·5] at day 0 vs 202·0 [174·8–233·4] at day 28) and neutralising antibody activity (seropositive patients 59% [IQR 39–83] at day 0 vs 82% [54–96] at day 28; seropositive controls 58% [41–79] at day 0 vs 92% [79–96] at day 28), was observed from day 0 to day 28, without further increases from day 28 to day 69 (at day 69 seropositive patients' GMT was 137·1 [116·2–161·9] and neutralising antibody activity was 79% [57–94]); and seropositive controls' GMT was 188·6 [167·4–212·6] and neutralising antibody activity was 92% [75–96]). By contrast, for seronegative patients and controls, the second dose was required for maximum response at day 69, which was lower in seronegative patients than in seronegative controls. GMTs in seronegative patients were 2·3 (95% CI 2·2–2·3) at day 0, 5·7 (5·1–6·4) at day 28, and 29·6 (26·4–33·3) at day 69, and in seronegative controls were 2·3 (2·1–2·5) at day 0, 10·6 (8·7–13·1) at day 28, and 71·7 (63·5–81·0) at day 69; neutralising antibody activity in seronegative patients was 15% (IQR 15–15) on day 0, 15% (15–15) at day 28, and 39% (15–65) at day 69, and in seronegative controls was 15% (15–15) at day 0, 24% (15–37) at day 28, and 61% (37–79) at day 69. Neither seronegative patients nor seronegative controls reached the GMT or antibody activity levels of seropositive patients at day 69. Interpretation By contrast with seronegative patients with autoimmune rheumatic diseases, seropositive patients have a robust response after a single dose of CoronaVac. Our findings raise the possibility that the reduced immunogenicity observed in seronegative patients might not be the optimum response potential to SARS-CoV-2 vaccination, and therefore emphasise the importance of at least a single booster vaccination in these patients. Funding Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and B3-Bolsa de Valores do Brasil. Translation For the Portuguese translation of the abstract see Supplementary Materials section.

Objective: To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases. Methods: A cross-sectional study included 343 adolescents with immunocompromising diseases and 108 healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). Results: The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00–7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08–3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12–4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93–0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95–0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19–0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16–0.77; p = 0.026) remained inversely associated with abnormal HI scores. Conclusion: The present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics.

Background Exercise has been suggested to prevent deterioration of health-related quality of life (HRQL) and overall health in pediatric rheumatologic diseases during the COVID-19 pandemic. Herein we describe the effects of a 12-week, home-based, exercise program on overall health and quality of life among quarantined patients with juvenile dermatomyositis (JDM). Method This prospective, quasi-experimental, mixed methods (qualitative and quantitative) study was conducted between July and December 2020, during the most restricted period of COVID-19 pandemic in Brazil. The home-based exercise program consisted of a 12-week, three-times-a-week, aerobic and strengthening (bodyweight) training program. Qualitative data were systematically evaluated. Strengths and Difficulties Questionnaire (SDQ), Pediatric Quality of Life Inventory (PedsQOL) and Pittsburgh Sleep Quality Index (PSQI) evaluate symptoms of mental health disorder, HRQL, and quality of sleep. Findings 11 patients (out of 27) met the inclusion criteria (91% female; mean ± SD age: 13.5 ± 3.2 years). Adherence to the intervention was 72.6%. Barriers to exercise involved poor internet connectivity, excessive weekly sessions, and other commitments. Even though not statistically significant, Self-report SDQ subscales Total Difficulties Score, Emotional Problems Score, and PedsQOL School Functioning Score improved after intervention (− 2.4; 95%confidence interval [CI] -5.1; 0.2, p = 0.06; − 1.0; 95%CI -2.2; 0.2, p = 0.09 and; 11.7; 95%CI -2.5; 25.8, p = 0.09, respectively). Remaining SDQ subscales were not altered. Six themes emerged from patients’ and parents’ comments (qualitative results). Patients engaged in exercise reported other health-related benefits including increased motivation, concentration and strength. Interpretation A home-based exercise program was associated with qualitative perceptions of improvements in overall health and HRQL by quarantined adolescents with JDM during COVID-19 pandemic. Lessons from this trial may help developing interventions focused on tackling physical inactivity in JDM.

Objective Coronavirus disease 2019 (COVID-19) has progressed rapidly around the world, reaching a lethality of up to 20% due to acute respiratory distress syndrome (ARDS). This latter condition is a relevant concern for systemic lupus erythematosus (SLE); however, data on this topic are limited to few case series. Our objective was to evaluate in hospitalized patients with SLE and with COVID-19-associated ARDS (confirmed by reverse transcription-polymerase chain reaction) the risk of mortality and combined poor outcomes (death, intensive care unit [ICU] admission, and/or mechanical ventilation [MV] use) and to compare with that of patients without SLE. Methods This is a nationwide cross-sectional study of patients with severe acute respiratory syndrome coronavirus 2 nested in the national Influenza Epidemiological Surveillance Information System (Sistema de Informacao de Vigilância Epidemiologica da Gripe [SIVEP-gripe]). Mortality rates, frequencies of ICU admissions, and MV use for 319 patients with SLE and 251 800 patients without SLE were calculated as well as relative risks (RRs). A fully adjusted multiple logistic regression was performed to adjust factors, such as age and well-known comorbidities, that might impact worse outcomes. Results Patients with SLE had an increased risk of death and combined poor outcome compared with patients without SLE (RR = 1.738, 95% confidence interval [CI]: 1.557-1.914, and RR = 1.391, 95% CI: 1.282-1.492, respectively). Among all investigated comorbidities, SLE yielded the higher risk of death and combined poor outcomes (RR = 2.205, 95% CI: 1.780-2.633, and RR = 1.654, 95% CI: 1.410-1.88, respectively). Conclusions This study provides novel evidence that patients with SLE hospitalized because of COVID-19 have significantly higher risks of death and poor outcomes compared with patients without comorbidities and patients with other comorbidities.

Objectives Toassess whether 18F-fluordeoxiglucose (18F-FDG) PET/MRI) with angiographic sequences can contribute to detecting vessel wall inflammation in patients with childhood-onset Takayasu’s arteritis (c-TA) under immunosuppressive therapy. Methods A three-centre cross-sectional study was conducted. 18F-FDG PET/MRI scans were performed in c-TA patients and in oncologic patients, who served as the control group. Clinical and laboratory characteristics were also analysed. Results Seventeen c-TA patients (65% females) between the ages of 6 and 21 years with a mean disease duration of 9.4 years were recruited. Only one patient presented clinical disease activity and six (35.6%) had increased ESR and/or CRP levels. The most frequent magnetic resonance angiography (MRA) findings were stenosis and thickening, observed in 82.4 and 70.6% of c-TA patients, respectively. 18F-FDG PET revealed 18F-FDG uptake greater than the liver in at least one arterial segment in 15 (88.2%) patients in a qualitative analysis and a median maximum standardized uptake value (SUVmax) of 3.22 (interquartile range 2.76–3.69) in a semi-quantitative analysis. c-TA patients presented significantly higher SUVmax values than oncologic patients (P Conclusion A state-of-the-art imaging modality was used in c-TA patients and revealed a strong arterial FDG uptake even in patients in apparent remission. We suppose that this finding may represent silent activity in the vessel wall; however, we cannot exclude the possibility of arterial remodelling. Importantly, a negative imaging scan may help in immunosuppression withdrawal in daily clinical practice.

To assess immunogenicity of a heterologous 4th dose of a mRNA (BNT162b2) SARS-CoV-2 vaccine in autoimmune rheumatic diseases (ARD) patients with poor/non-response to inactivated vaccine (Sinovac-CoronaVac).164 ARD patients who were COVID-19 poor/non-responders (negative anti-SARS-CoV-2 S1/S2 IgG and/or neutralising antibodies-NAb) to the 3rd dose of Sinovac-CoronaVac received an additional heterologous dose of mRNA (BNT162b2) three months after last dose. IgG and NAb were evaluated before and after the 4th dose.Significant increases were observed after 4th dose in IgG (66.4% vs 95.1%, p0.001), NAb positivity (5.5% vs 83.5%, p0.001) and GMT (29.5 vs 215.8 AU/ml, p0.001), and 28 (17.1%) remained poor/non-responders. Patients with negative IgG after 4th dose were more frequently under rituximab (p= 0.001). Negative NAb was associated with older age (p= 0.015), rheumatoid arthritis (p= 0.002), systemic sclerosis (p= 0.026), leflunomide (p= 0.016), and rituximab use (p= 0.007). In multiple logistic regression analysis, prednisone dose ≥7.5 mg/day (OR = 0.34; p= 0.047), leflunomide (OR = 0.32, p= 0.036) and rituximab use (OR = 0.19, p= 0.022) were independently associated with negative NAb after the 4th vaccine dose.This is the largest study to provide evidence of a remarkable humoral response after the 4th dose of heterologous mRNA SARS-CoV-2 vaccination in ARD patients with poor/no-response to the 3rd dose of an inactivated vaccine. We further identified that treatment, particularly rituximab and prednisone, impaired antibody response to this additional dose.ClinicalTrials.gov, https://clinicaltrials.gov, CoronavRheum #NCT04754698.

Objective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). Results: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05–0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05–0.88, p = 0.034). After six months (D69–D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).

This study aimed to investigate whether a single bout of exercise prior to the homologous booster dose of a SARS-CoV-2 inactivated vaccine (Sinovac-CoronaVac) could enhance immunogenicity in patients with dysfunctional immune system. This was a randomized controlled trial (1:1) within a single-arm, phase 4 vaccination trial, conducted in São Paulo, Brazil. Patients with spondyloarthritis assigned to the intervention group performed an exercise bout comprising three unilateral strength exercises involving eccentric and concentric contractions. After exercising, patients remained at rest for 1 h prior to vaccination, which was applied to the exercised arm. The control group remained at rest before vaccination. Immunogenicity was assessed before (Pre) and one month after (Post) the booster dose using seropositivity rates of total anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG (GMT), frequency of NAb positivity, and NAb activity. Before the booster dose, 16 patients from the exercise group and 16 patients from the control group exhibited seropositivity for IgG (59% vs. 57.1%), one month after the booster dose, seropositivity occurred in 96% vs. 100% of the cases (p = 0.84, group by time interaction). Only 10 patients from the exercise group and 12 patients from the control group showed positive NAb serology at Pre (37% vs. 42.8%). One month following the booster, NAb positivity was 96% vs. 93% (p = 0.41, group-by-time interaction). GMT was comparable between groups at Pre (p > 0.05). At Post, GMT increased similarly in both groups (exercise: 56.9%; control: 57.9%), with no group-by-time interaction (p = 0.82; estimated mean difference between groups at Post [EMD]: -40.4 UA/mL, 95%CI: -327, 246 UA/mL). Likewise, NAb activity was similar between groups at Pre and increased similarly in both of them as a result of the booster (47.5% vs. 39.9%), with no group-by-time interaction (p = 0.99; EMD: -6.19%, 95%CI: -17; 4.6%). In conclusion, a single bout of exercise did not enhance immunogenicity to a homologous booster dose of an inactivated SARS-CoV-2 vaccine among patients with spondyloarthritis. Studies assessing exercise as an adjuvant to first or second doses remain necessary.

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

ObjectivesTo evaluate the effect on immunogenicity and safety of 2-week methotrexate(MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in rheumatoid arthritis(RA) patients.MethodsThis was a single-center, prospective, randomized, investigator-blinded, intervention study (#NCT04754698, CoronavRheum), including adult RA patients(stable CDAI10 at D28).ResultsRandomization included 138 patients with 9 exclusions(5 COVID-19, 4 protocol violations). Safety evaluation included 60(MTX-hold) and 69(MTX-maintain) patients. Further exclusions consisted of 27 patients[13(21.7%) vs. 14(20.3%),p=0.848] with positive baseline IgG/NAb and 10 patients(21.3%) in MTX-hold with CDAI>10 at D28. At D69, a higher increase in SC[29(78.4%) vs 30(54.5%),p=0.019] was observed in MTX-hold(n=37) in comparison to MTX-maintain(n=55), with parallel augmentation in GMT[34.2(25.2-46.4) vs 16.8(11.9-23.6),p=0.006]. No differences were observed for NAb positivity[23(62.2%) vs 27(49.1%),p=0.217]. Longitudinal variations in disease activity scores were alike in both groups(CDAI,p=0.144; DAS28-CRP,p=0.718).ConclusionWe provided novel data that 2-week MTX withdrawal after each vaccine dose improves anti-SARS-CoV-2 immunogenicity. The comparable longitudinal variations of disease activity in both groups suggest that discontinuation is a feasible and efficient strategy in well-controlled RA patients, and may be even safer for vaccines with longer interval between doses or single dose schedules.FundingFAPESP/CNPq/B3-Bolsa de Valores-Brasil.

The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2nd dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6 months compared to 6 weeks after 2nd vaccine dose for decay evaluation. Secondary outcomes are presence of neutralizing antibodies, percent inhibition by neutralizing, geometric mean titers and cumulative incident cases at 6 months after 2nd dose. Anti-S1/S2 IgG positivity and titers reduce to 23.8% and 38% in patients (p p p p

Made available in DSpace on 2022-04-29T08:46:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Objective: To evaluate if the 2019-European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria at diagnosis of childhood-onset systemic lupus erythematosus (cSLE) are associated with higher rates of early damage scored by Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI). Methods: This retrospective multicenter study included 670 cSLE patients with ≤5 years of disease duration. All patients fulfilled both 2019-EULAR/ACR and 1997-ACR classification criteria. Total score of 2019-EULAR/ACR criteria and each of its specific domains were assessed at diagnosis as predictors of damage accrual at the last visit, according to the presence of any organ damage (defined by SDI ≥ 1). Results: Median disease duration was 2.8 (IQR 1.8–3.8) years and 200 (29.9%) patients had at least one organ damage (SDI ≥ 1). The most frequent domains were neuropsychiatric (12%), renal (7%), and musculoskeletal (6%). There was a higher frequency of renal (58% vs 43%, p = 0.0004) and neuropsychiatric domain (21% vs 7%, p < 0.0001) of 2019-EULAR/ACR criteria in patients with damage (SDI ≥ 1) compared to those without damage (SDI = 0). Patients scoring renal or neuropsychiatric domains of the 2019-EULAR/ACR criteria at diagnosis were associated with renal damage (odds ratio 9.701, 95% confidence interval 3.773–24.941, p < 0.001) or neuropsychiatric damage (OR 9.480, 95% CI 5.481–16.399, p25 was associated with more overall (SDI ≥ 1) (38% vs 25%, p = 0.0002) and renal damage (11% vs 5%, p = 0.023). Conclusions: The 2019-EULAR/ACR criteria at diagnosis were associated with a higher rate of early damage in cSLE patients, especially for renal and neuropsychiatric damage. Of note, damage was particularly associated with high disease activity at diagnosis and 2019-EULAR/ACR score >25. Pediatric Rheumatology Unit Children’s Institute Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Division of Rheumatology Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Pediatric Rheumatology Unit Universidade Federal de Sao Paulo Pediatric Rheumatology Division Sao Paulo State University (UNESP) Pediatric Rheumatology Unit Janeiro Federal University (IPPMG-UFRJ) Pediatric Rheumatology Unit Hospital da Criança de Brasília Jose Alencar Post-graduation Program in Medical Science and Rheumatology Unit University of Brasilia Pediatric Rheumatology Unit Ribeirao Preto Medical School University of Sao Paulo Pediatric Rheumatology Unit Hospital Geral de Fortaleza Pediatric Rheumatology Unit University of Campinas (UNICAMP) Pediatric Rheumatology Unit Pedro Ernesto University Hospital Pediatric Rheumatology Unit Irmandade da Santa Casa de Misericórdia de Sao Paulo Rheumatology Division - Universidade Federal do Rio de Janeiro Hospital Universitário Clementino Fraga Filho Pediatric Rheumatology Unit Federal University of Pará Pediatric Rheumatology Unit Federal University of Bahia Pediatric Rheumatology Unit Hospital Menino Jesus Pediatric Rheumatology Unit Federal University of Pernambuco Pediatric Rheumatology Unit Federal University of Mato Grosso do Sul Pediatric Rheumatology Division Sao Paulo State University (UNESP)

OBJECTIVE: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI). RESULTS: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p

Background: Coronavirus disease 19 (COVID-19) has an increased risk of coagulopathy with high frequency of antiphospholipid antibodies (aPL). The recent reports of thrombosis associated with the adenovirus-based vaccines raises concern that SARS-CoV-2 immunization in primary antiphospholipid syndrome (PAPS) patients may trigger a dysregulated immune response with possible clotting complications. Therefore, the objectives of this study were to assess immunogenicity, aPL production and safety of Sinovac-Coronavac in PAPS patients.Methods: This prospective controlled phase 4 study of SARS-CoV-2-naïve PAPS patients and a control group (CG) consisted of a two-dose Sinovac-CoronaVac (D0/D28) and blood collection before vaccination (D0), at D28 and 6 weeks after second dose (D69) for immunogenicity/aPL levels. Outcomes were seroconversion (SC) rates of anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies (NAb) at D28/D69. Safety and aPL production were also assessed. Results: Forty-four PAPS patients and 132 CG had comparable age (p=0.982) and sex (p>0.999). At D69, both groups had high and comparable SC (83.9% vs. 93.5%, p=0.092) and GMT [50.2(95%CI 34.5-73.2) vs. 61.7 (95%CI 52.8-72.3), p=0.249] as well as NAb positivity (77.4% vs. 78.7%, p=0.440), and NAb-activity [64.3% (49.0-77.0) vs. 60.9% (45.6-81.3), p=0.689]. Of note, for D28, the antibody response was very low and also similar in both groups SC (25.8% vs. 30.6% p=0.609). Antiphospholipid levels remained stable throughout the study at D0 vs D28 vs D69 (IgG aCL, p=0.058; IgM aCL, p=0.091; IgG aβ2GPI, p=0.513 and IgM aβ2GPI, p=0.468). Thrombotic event up to 6 months or other moderate/severe side effects were not observed.Conclusions: We provide novel evidence that Sinovac-CoronaVac vaccine has a high immunogenicity and excellent safety profile in PAPS. We further demonstrated that this vaccine did not trigger thrombosis or induced changes in aPL-related antibodies production. Our findings strongly support the recommendation of SARS-CoV-2 vaccination for PAPS patients.Trial registration: ClinicalTrials.gov - Identifier: NCT04754698 first registered on February 8th, 2021.

Objective: To assess intermittent abdominal pain in IgA vasculitis patients and its relation to demographic data, clinical manifestations and treatments. Methods: A retrospective cohort study included 322 patients with IgA vasculitis (EULAR/PRINTO/PRES criteria) seen at the Pediatric Rheumatology Unit in the last 32 years. Sixteen patients were excluded due to incomplete data in medical charts. Intermittent abdominal pain was characterized by new abdominal pain after complete resolution in the first month of disease. Results: Intermittent abdominal pain was observed in 35/306 (11%) IgA vasculitis patients. The median time between first and second abdominal pain was 10 days (3–30 days). The main treatment of intermittent abdominal pain included glucocorticoid [n=26/35 (74%)] and/or ranitidine [n=22/35 (63%)]. Additional analysis showed that the frequency of intermittent purpura/petechiae (37 vs. 21%; p=0.027) and the median of purpura/petechiae duration [20 (3–90) vs. 14 (1–270) days; p=0.014] were significantly higher in IgA vasculitis patients with intermittent abdominal pain compared to those without. Gastrointestinal bleeding (49 vs. 13%; p

Objectives To evaluate immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in systemic autoimmune myopathies (SAMs) and the possible influence of baseline disease parameters, comorbidities and therapy on immune response. Methods This prospective controlled study included 53 patients with SAMs and 106 non-immunocompromised control group (CTRL). All participants received two doses of the Sinovac-CoronaVac vaccine (28-day interval). Immunogenicity was assessed by anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC), anti-S1/S2 IgG geometric mean titre (GMT), factor increase GMT (FI-GMT), neutralizing antibodies (NAb) positivity, and median neutralizing activity after each vaccine dose (D0 and D28) and six weeks after the second dose (D69). Participants with pre-vaccination positive IgG serology and/or NAb and those with RT-PCR confirmed COVID-19 during the protocol were excluded from immunogenicity analysis. Results Patients and CTRL had comparable sex (P>0.99) and age (P=0.90). Immunogenicity of 37 patients and 79 CTRL-naïve participants revealed at D69, a moderate but significantly lower SC (64.9% vs 91.1%, P0.05). Conclusion Sinovac-CoronaVac is safe and has a moderate short-term immunogenicity in SAMs, but reduced compared with CTRL. We further identified that immunosuppression is associated with diminished NAb positivity. Trial registration COVID-19 CoronaVac in Patients With Autoimmune Rheumatic Diseases and HIV/AIDS (CoronavRheum), http://clinicaltrials.gov/ct2/show/NCT04754698

Resumo Fundamento A pandemia da COVID-19 representa uma enorme carga para o sistema de saúde do mundo. Apesar de pacientes pediátricos terem sido relativamente poupados em comparação a adultos, estudos recentes mostraram um número crescente de pacientes críticos com Síndrome Inflamatória Multisistêmica Pediátrica (SIM-P) com disfunção cardiovascular importante. No entanto, pouco se conhece a respeito da relação entre anormalidades cardíacas e biomarcadores inflamatórios e de coagulação. Objetivos Investigar anormalidades ecocardiográficas em pacientes pediátricos com COVID-19 admitidos em um hospital terciário. Métodos Este foi um estudo longitudinal retrospectivo, baseado na revisão de prontuários médicos e ecocardiogramas de pacientes (0-19 anos) admitidos em um hospital terciário entre 30 de março e 30 de junho de 2020. Para a análise estatística, o nível de significância foi estabelecido em 5% (p+2,5). Anormalidades ecocardiográficas foram significativamente associadas com SIM-P, admissão na unidade de terapia intensiva pediátrica, suporte ventilatório/vasoativo, e morte ( p

CoronaVac(SARS-CoV-2 inactivated vaccine) has been largely used as the main immunogen for COVID-19 in several countries. However, its immunogenicity in immunocompromised individuals has not been established. This was a prospective controlled study of 910 adult ARD patients and 182 age- and sex-matched control group(CG) who received two doses of CoronaVac in a 28-days interrval. Anti-SARS-Cov-2 IgG and neutralizing antibodies were assessed at each vaccine shot and 6 weeks after the 2nd dose. Vaccine adverse events(AE) were similar in both groups. We observed significant lower anti-SARS-Cov-2 IgG seroconversion(70.4% vs. 95.5%,p

Background It is currently unknown whether patients with childhood-onset Takayasu disease (c-TA) are prone to physical inactivity and poor aerobic capacity. In this study, we assessed physical activity levels and cardiorespiratory fitness along with health-related quality of life (HRQL) and various traditional and non-traditional risk factors in patients with c-TA vs. healthy controls. Methods c-TA patients with non-active disease (n = 17) and age- and sex-matched healthy controls (n = 17) were enrolled in the study. We assessed physical activity levels, aerobic capacity, body composition, systemic inflammation, cardiometabolic markers, disease-related parameters, and HRQL. Results c-TA patients showed greater time spent in sedentary behavior (P = 0.010), and lower moderate-to-vigorous physical activity (P > 0.001) and lower step counts per day (P > 0.001). VO2peak (P P = 0.016) were significantly lower in patients with c-TA and they had worse HRQL in physical domain (P P ≤ 0.05). Conclusions c-TA patients exhibited reduced physical activity levels and aerobic capacity, worse cardiometabolic risk factors and HRQL parameter compared with healthy peers. Physical inactivity and aerobic deconditioning emerge as potentially novel risk factors for c-TA. The role of physical activity interventions in preventing poor outcomes and improving HRQL in c-TA remains to be explored.

Made available in DSpace on 2021-06-25T11:03:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Purpose: To present a national guideline for ophthalmologic care and surveillance of juvenile idiopathic arthritis-associated uveitis (JIA-uveitis).Methods: Review article based on medical literature and the experience of an Expert Committee composed of members of the Brazilian Society of Pediatric Ophthalmology/Brazilian Council of Ophthalmology and the Brazilian Society of Pediatrics/Brazilian Society of Rheumatology. Studies with a high level of evidence were selected by searching the PubMed/Medline database. The final document was approved by the experts.Results: The main recommendations are that children/adolescents with JIA should undergo screening according to their risk factors. Ophthalmological checkups should also consider ocular inflammation and therapy. Topical glucocorticoids should be the first line of therapy, with systemic glucocorticoids acting as bridge treatments in severe uveitis. Methotrexate should be the first-line systemic therapy and anti-tumor necrosis factor (anti-TNF alpha) the second for uncontrolled uveitis.Conclusions: This evidence-based guideline for JIA-uveitis will be useful for both ophthalmology and rheumatology practice. Ophthalmology Department Instituto Nacional De Saúde Da Mulher Da Criança E Do Adolescente Fernandes Figueira- Fundação Oswaldo Cruz Brazilian Society of Pediatric Ophthalmology (SBOP) Brazilian Council of Ophthalmology (CBO) Ophthalmology Department, Hospital De Olhos Do Paraná Brazilian Society of Pediatrics (SBP) Ophthalmology Department, Santa Casa De Misericórdia De Ophthalmology and Visual Science Department Federal University of Sao Paulo – UNIFESP Pediatric Rheumatology Unit Children’s Institute Hospital Das Clinicas HCFMUSP Faculdade De Medicina Universidade De Sao Paulo Brazilian Society of Rheumatology (SBR) Pediatric Department Santa Casa De Misericórdia De Porto Alegre Pediatric Rheumatology Division São Paulo State University (UNESP) Pediatric Rheumatology Unit Federal University of São Paulo – UNIFESP Pediatric Department Instituto De Puericultura E Pediatria Martagão Gesteira - IPPMG/Federal University of Rio De Janeiro - UFRJ Pediatric Rheumatology Division São Paulo State University (UNESP)

CoronaVac, an inactivated SARS-CoV-2 vaccine, has been approved for emergency use in several countries. However, its immunogenicity in immunocompromised individuals has not been well established. We initiated a prospective phase 4 controlled trial (no. NCT04754698, CoronavRheum) in 910 adults with autoimmune rheumatic diseases (ARD) and 182 age- and sex-frequency-matched healthy adults (control group, CG), who received two doses of CoronaVac. The primary outcomes were reduction of ≥15% in both anti-SARS-CoV-2 IgG seroconversion (SC) and neutralizing antibody (NAb) positivity 6 weeks (day 69 (D69)) after the second dose in the ARD group compared with that in the CG. Secondary outcomes were IgG SC and NAb positivity at D28, IgG titers and neutralizing activity at D28 and D69 and vaccine safety. Prespecified endpoints were met, with lower anti-SARS-Cov-2 IgG SC (70.4 versus 95.5%, P < 0.001) and NAb positivity (56.3 versus 79.3%, P < 0.001) at D69 in the ARD group than in the CG. Moreover, IgG titers (12.1 versus 29.7, P < 0.001) and median neutralization activity (58.7 versus 64.5%, P = 0.013) were also lower at D69 in patients with ARD. At D28, patients with ARD presented with lower IgG frequency (18.7 versus 34.6%, P < 0.001) and NAb positivity (20.6 versus 36.3%, P < 0.001) than that of the CG. There were no moderate/severe adverse events. These data support the use of CoronaVac in patients with ARD, suggesting reduced but acceptable short-term immunogenicity. The trial is still ongoing to evaluate the long-term effectiveness/immunogenicity.

Dry eye disease (DED) is common in Rheumatoid Arthritis (RA) patients. The application of conjunctival goblet cell count as a clinical biomarker to diagnose and respond to treatment can take place in rheumatoid arthritis patients under TNF-inhibitors (TNFi) therapy. This study aimed to investigate the ocular surface parameters and the long-term effects of TNFi therapy on ocular surface features and goblet cell count of rheumatoid arthritis patients. At baseline, rheumatoid arthritis patients eligible to TNFi were compared to healthy controls (similar age/gender), regarding Ocular Surface Disease Index (OSDI) questionnaire, Schirmer I test, tear break-up time test, vital dye staining of the ocular surface, and conjunctival impression cytology. DED severity grade, impression cytology score, and goblet cell count were analyzed. Rheumatoid arthritis patients were followed after three (3 M) and 12 months (12 M), during TNFi treatment. Sixteen rheumatoid arthritis patients and 24 controls were compared: a higher frequency of abnormal OSDI (68.8% vs. 16.7%, p = 0.002), Schirmer’s test p = 0.042), meibomian gland dysfunction (50% vs. 8.3%, p = 0.007), abnormal impression cytology (75% vs. 8.3%, p p 2 vs. 742 (562–863) cells/mm2, p = 0.004]. The presence of Meibomian gland dysfunction was associated with higher disease activity scores (p p = 0.001], and an improvement in impression cytology score [1 (0.5–2) vs. 1 (0–1), p = 0.031] and in goblet cell count [325 (274–707) vs. 931 (656–1,244), p p = 0.047]. Multifactorial DED is frequent in RA patients, comprising aqueous, lipid, and mucin components. TNFi prompt improves tear production and recovers the goblet cells, which can be a biomarker of the pathological process and response to therapy in this population.

Made available in DSpace on 2021-06-25T12:24:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-11 Background: Concerns about the safety and efficacy of vaccines in patients with autoimmune diseases (AID) have led to contradictions and low vaccination coverage in this population, who are at a higher risk of infections, including by human papillomavirus (HPV). Although HPV vaccines have been recommended for immunocompromised patients, there is still a lack of data to support its use for AID patients, such as juvenile dermatomyositis (JDM) patients. The aim of this study was to assess the safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine in a cohort of JDM patients. Methods: JDM patients aged from 9 to 20 years and healthy controls (HC) were enrolled to receive a 3-dose schedule of qHPV vaccine from March/2014 to March/2016. Study visits were performed before the first dose, 1 month after the second and third doses, and 6 months after the third dose. Participants completed a diary of possible adverse events for 14 days following each dose of vaccination (AEFV). Disease activity and current therapy were analyzed at each visit for JDM patients. In addition, serum samples from all participants were collected to test antibody concentrations against HPV16 and 18 at each visit. Participant recruitment was conducted in ten Brazilian centres. From 47 eligible JDM patients and 41 HC, 42 and 35, respectively, completed the 3-dose schedule of the vaccine, given that five JDM patients and two HC had received doses prior to their inclusion in the study. Results: The AEFVs presented by the participants were mild and in general did not differ between JDM and HC groups. No severe AEFVs were related to the vaccination. Disease activity was stable, or even improved during the follow-up. One month after the third dose of the vaccine the JDM group presented seropositivity of 100% for HPV16 and 97% for HPV18, similarly to the HC group, who presented 100% for both serotypes (p = 1.000). Six months after the third dose the seropositivity for the patient group was 94% for both HPV types. Conclusions: The HPV vaccination in this cohort of JDM patients was safe and immunogenic. Since the seropositivity against HPV16 and 18 was very high after the 3-dose schedule, this regimen should be recommended for JDM patients. Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Paediat Immunol & Rheumatol, Utrecht, Netherlands Univ Fed Parana, Hosp Clin, Dept Pediat, Gen Carneiro St 68,181, BR-80060900 Curitiba, Parana, Brazil Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Paediat, Sao Paulo, Brazil Univ Fed Sao Paulo, Dept Prevent Med, Sao Paulo, Brazil Univ Sao Paulo, Fac Med, Hosp Clin, Dept Paediat Rheumatol,Inst Crianca, Sao Paulo, Brazil Univ Fed Sao Paulo, Dept Paediat Rheumatol, Sao Paulo, Brazil Hosp Estadual Infantil Nossa da Senhora, Dept Paediat Rheumatol, Vitoria, ES, Brazil Univ Fed Rio de Janeiro, Inst Puericultura & Pediat Martagao Gesteira IPPM, Dept Paediat Rheumatol, Rio De Janeiro, Brazil Univ Estado Rio De Janeiro, Dept Paediat Rheumatol, Rio De Janeiro, Brazil Hosp Infantil Albert Sabin, Dept Paediat Rheumatol, Fortaleza, Ceara, Brazil Univ Florida, Dept Paediat Immunol & Rheumatol, Coll Med, Gainesville, FL 32611 USA Hosp Crianca Brasilia Jose Alencar, Dept Paediat Rheumatol, Brasilia, DF, Brazil Univ Estadual Campinas, Dept Paediat Rheumatol, Sao Paulo, Brazil Univ Fed Rio de Janeiro, Dept Paediat Rheumatol, Rio De Janeiro, Brazil Univ Estadual Paulista, Dept Paediat Rheumatol, Botucatu, SP, Brazil Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Paediat Rheumatol, Sao Paulo, Brazil Natl Inst Publ Hlth & Environm RIVM, Ctr Infect Dis Control, Bilthoven, Netherlands Hosp Canc Barretos, Fac Ciencias Saude Dr Paulo Prata FACISB, Sao Paulo, Brazil Hosp Canc Barretos, Inst Ensino & Pesquisa IEP, Sao Paulo, Brazil Univ Estadual Paulista, Dept Paediat Rheumatol, Botucatu, SP, Brazil

Made available in DSpace on 2019-10-06T15:31:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-11-23. Added 1 bitstream(s) on 2021-07-15T15:23:32Z : No. of bitstreams: 1 S2523-31062018000100228.pdf: 598953 bytes, checksum: c510a60909892e9f6d7f26d4469f267b (MD5) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) OBJECTIVE: To evaluate prevalence, clinical manifestations, laboratory abnormalities and treatment in a multicenter cohort study including 847 childhood-onset systemic lupus erythematosus (cSLE) patients with and without diffuse alveolar hemorrhage (DAH), as well as concomitant parameters of severity. METHODS: DAH was defined as the presence of at least three respiratory symptoms/signs associated with diffuse interstitial/alveolar infiltrates on chest x-ray or high-resolution computer tomography and sudden drop in hemoglobin levels. Statistical analysis was performed using Bonferroni correction (p

To assess prospectively luteinized unruptured follicle (LUF) syndrome in juvenile idiopathic arthritis (JIA) patients with and without non-steroidal anti-inflammatory drugs (NSAIDs) and healthy controls. Twenty-three adolescent and young adult female JIA patients (ILAR criteria) and 11 female healthy subjects were studied by pelvic ultrasound monitoring for follicular development and ovulation in one menstrual cycle. LUF syndrome was prospectively investigated by pelvic ultrasound with a dominant ovarian follicle without signs of follicular rupture, with elevation of serum progesterone in the luteal phase of the menstrual cycle and luteinizing hormone (LH) detected in the urine. Comparison between JIA patients with (n = 8) vs. without NSAIDs (n = 15) and healthy controls (n = 11) revealed that LUF syndrome was significantly higher in the former group (2 (25%) vs. 0% vs. 0%, p = 0.049). These two patients with LUF syndrome had normal menstrual cycles without reduced ovarian reserve, and they were under naproxen 500 mg bid during the menstrual cycle. Disease duration was comparable in JIA with and without NSAIDs [19.8 (4.4–25) vs. 13 (3.1–33) years, p = 0.232]. Further comparison between JIA patients with and without NSAIDs and healthy controls showed similar mean anti-Mullerian hormone levels (p = 0.909), estradiol (p = 0.436), FSH (p = 0.662), LH (p = 0.686), and mean antral follicle count (p = 0.240) and ovarian volume (p = 0.363). No differences were evidenced in three groups regarding Caucasian race, body mass index, duration, and length of menstrual cycles (p > 0.05). This is the first study to identify that JIA patients have a high frequency of LUF without impaired ovarian reserve. Future prospective studies are necessary to determine if chronic/continuous use of NSAIDs in JIA will have an impact in these patients’ fertility.

Background Brazil faced a yellow fever(YF) outbreak in 2016–2018 and vaccination was considered for autoimmune rheumatic disease patients(ARD) with low immunosuppression due to YF high mortality. Objective This study aimed to evaluate, prospectively for the first time, the short-term immunogenicity of the fractional YF vaccine(YFV) immunization in ARD patients with low immunossupression. Methods and Results A total of 318 participants(159 ARD and 159 age- and sex-matched healthy controls) were vaccinated with the fractional-dose(one fifth) of 17DD-YFV. All subjects were evaluated at entry(D0), D5, D10, and D30 post-vaccination for clinical/laboratory and disease activity parameters for ARD patients. Post-vaccination seroconversion rate(83.7%vs.96.6%, p = 0.0006) and geometric mean titers(GMT) of neutralizing antibodies[1143.7 (95%CI 1012.3–1292.2) vs.731 (95%CI 593.6–900.2), p0.05). Conclusion Fractional-dose 17DD-YF vaccine in ARD patients resulted in a high rate of seroconversion rate(>80%) but lower than controls, with a longer but less intense viremia. This vaccine was immunogenic, safe and did not induce flares in ARD under low immunosuppression and may be indicated in YF outbreak situations and for patients who live or travel to endemic areas. Trial registration This clinical trial was registered with Clinicaltrials.gov (#NCT03430388)., Author summary Yellow fever is a viral hemorragic fever with high mortality rate and the vaccine is a remarkably successful way of preventing it. As a live attenuated virus vaccine, it is not recommended for rheumatic and other immunossupressed patients in general. However, in an outbreak scenario, the risk of dying of the disease can be higher than the risk of a vaccine serious adverse event. In 2018, the fractional-dose yellow fever vaccine was offered to the hospital employees and to the rheumatic patients without or with low immunossupression therapy in Hospital das Clinicas of University of São Paulo, during the yellow fever outbreak in São Paulo, Brazil. In order to optimize the yellow fever vaccine (YFV) supply, the fractional-dose (corresponding to one fifth) was adopted in the public vaccine campaign. This is the first study evaluating the primary vaccination with fractional-dose YFV in autoimmune rheumatic diseases(ARD) patients (n = 159) under low immunosuppression. Most vaccinated participants were able to produce enough neutralizing antibodies to be protected against yellow fever (seroconversion rate of 84% versus 96% in healthy controls). Neither activity of the rheumatic disease or serious adverse event was identified during the 30 days of followup after the vaccination.

In this randomized double-blind placebo-controlled 24-week trial, cholecalciferol supplementation at 50,000 IU/week effectively improved bone microarchitecture parameters in juvenile-onset systemic lupus erythematosus (JoSLE) patients, as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia site. An increase in the trabecular number and a decrease in the trabecular separation were observed, suggesting that vitamin D supplementation may be recommended for JoSLE patients with its deficiency.Vitamin D has an important effect on bone but there are no trials that directly address the boosting of serum levels of 25-hydroxyvitamin D (25OHD) in bone microarchitecture in JoSLE patients. The aim of this study was to evaluate the effect of vitamin D supplementation on bone microarchitecture parameters using HR-pQCT in JoSLE patients.This study was a randomized double-blind placebo-controlled 24-week trial. Forty female JoSLE patients were randomized (1:1) to receive oral cholecalciferol at 50,000 IU/week (JoSLE-VitD) or placebo (JoSLE-PL). The medications remained stable throughout the study. Serum levels of 25OHD were measured using a radioimmunoassay. The bone microarchitecture and volumetric bone density were analyzed using HR-pQCT at tibia site.At baseline, the groups were similar with respect to their age, body mass index, organ involvement, glucocorticoid dose, immunosuppressant use, serum 25OHD levels, and HR-pQCT parameters. After 24 weeks, higher 25OHD levels were observed in the JoSLE-VitD group compared to the JoSLE-PL group [31.3 (8.6) vs. 16.5 (5.8) ng/mL, p 0.001]. An increase in the trabecular number [∆Tb.N 0.16 (0.24) vs. 0.03 (0.19) 1/mm, p = 0.024] and a decrease in the trabecular separation [∆ThSp -0.045 (0.067) vs. 0.001 (0.009) mm, p = 0.017] were found in the JoSLE-VitD group compared to the JoSLE-PL group at tibia site. No differences were observed in other structural parameters [trabecular (Tb.Th) or cortical thickness (Ct.Th)], volumetric bone mineral densities, cortical porosity, and biomechanical parameters (p 0.05).This study suggests that cholecalciferol supplementation for 24 weeks effectively improved the bone microarchitecture parameters, mainly the trabecular number, in JoSLE patients.NCT01892748.

To compare clinical and laboratorial features between childhood-onset systemic lupus erythematosus (cSLE) and adult SLE (aSLE) at concomitant diagnosis of immune thrombocytopenic purpura (ITP).This study evaluated 56 cSLE and 73 aSLE patients regularly followed at Pediatric and Rheumatology Divisions of the same University hospital with ITP (platelets count100,000/mmMedian current age was 11.6 and 27.3 years in cSLE and aSLE, respectively. cSLE had a higher frequency of ITP compared to aSLE (17% vs. 4%, p .0001) and the former group had more hemorrhagic manifestations (36% vs. 16%, p = .0143). Constitutional symptoms and reticuloendothelial manifestations (p .05), as well as pericarditis (25% vs. 10%, p = .029) and central nervous system (CNS) involvement (30% vs. 14%, p = .029) were more common in cSLE. Conversely, in aSLE, ITP was solely associated with cutaneous and articular involvements (p .05). Concerning treatment, intravenous methylprednisolone, intravenous immunoglobulin, blood transfusion and platelets transfusion were more frequently used in the cSLE population (p .05).ITP at cSLE has distinct features compared to aSLE with a more severe presentation characterized by concomitant constitutional/reticuloendothelial manifestations, CNS involvement and hemorrhagic manifestation. These findings reinforce the need for a more aggressive treatment in this age group.

To assess the rate of serious and/or opportunistic infections in juvenile idiopathic arthritis (JIA) patients from a single tertiary center under biologic therapy and to identify possible risk factors associated to these complications.A total of 107 JIA patients followed at the biologic therapy center of our tertiary university hospital using a standardized electronic database protocol including demographic data, clinical and laboratorial findings and treatment at baseline and at the moment of infection. Opportunistic infections included tuberculosis, herpes zoster and systemic mycosis.A total of 398 patient-yrs(py) were included. The median time of biologic exposure was 3.0 years (0.15-11.5). We observed 35 serious/opportunistic infectious events in 27 (25%) patients: 31(88.6%) were serious infections and four (11.4%) opportunistic infections. Serious/opportunistic infections rates were 10.6/100py for ETN, 10.9/100py for ADA, 2.6/100py for ABA and 14.8/100py for TCZ. Comparison of 27 patients with and 80 without infection showed a higher frequency of systemic-onset JIA, lower age at biologic therapy initiation and a history of previous serious infection (p .05) in the former group.This study demonstrated a high rate of serious infections in JIA patients under biologic therapy in a real-life setting. Systemic-onset JIA, lower age at biologic therapy start and history of previous serious infections were important risk factors for these complications. Also, higher rates of severe infections comparing to the former studies was possibly due to elevated MTX doses in our patients.

Objective To assess the possible effect of therapy, disease subtype and severity on H1N1 immunogenicity in patients with SSc. Methods Ninety-two patients and 92 age- and gender-matched healthy controls received adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Blood samples were collected immediately before and 3 weeks after vaccination to evaluate antibody responses to the H1N1 virus. Efficacy was assessed by seroprotection (SP) and seroconversion (SC) rates and the factor increase in geometric mean antibody titre. Participants received a 21-day symptom diary card and were instructed to report local and systemic adverse events. Results SSc patients were predominantly females (91%) and 61% had limited SSc, 12% had severe skin involvement and 57.6% were on immunosuppressive (IS) therapy. SSc patients and controls presented comparable overall SP (P = 0.20) and SC (P = 0.61) rates. Further evaluation of the possible effect of disease and therapy revealed similar rates of SP and SC in patients with dcSSc vs lcSSc (SP P = 0.62 and SC P = 0.66), severe vs mild/moderate skin involvement (SP P = 1 and SC P = 0.45) and with vs without IS (SP P = 0.26 and SC P = 0.10). The frequency of mild local and minor systemic reactions was similar in patients with dcSSC vs lcSSc (P = 0.70 vs 0.32) and in those with and without severe skin involvement (P = 0.59 vs 0.28). Conclusion The non-adjuvanted influenza H1N1 virus vaccine proved to be safe and effective, independent of SSc clinical subtype, disease severity or therapy. These latter factors do not seem to contribute to mild adverse events observed in SSc. Our data support the annual influenza vaccination recommendation for these patients. Trial registration ClinicalTrials.gov (http://clinicaltrials.gov), NCT01151644.