ABSTRACT
Background. Several studies and cohorts with adult populations with rheumatic diseases (RD) were performed since pandemic outbreak. RD patients were more susceptible to infections and may develop severe forms of COVID-19, since they present immunosuppressive mechanisms inherent to the disease itself and to its treatment. Healthy children and adolescents seem to be less infected and present milder diseases. However, juvenile dermatomyositis patiets and immunosuppressed children have not been extensively studied. The objectives of the study are to evaluate asymptomatic SARS-CoV-2 infection in pediatric RD patients, to identify the risk factors related to contagion and to describe demographics and the profile of COVID-19 in juvenile dermatomyositis (JDM) patients followed. Methods. A cross-sectional study was conducted in March 2021, including 77 pediatric RD patients followed at a Brazilian tertiary hospital and 45 healthy controls. Data was obtained through a questionnaire applied to outpatients during the month of March 2021, before the vaccine, and contained demographic data, symptoms compatible with COVID-19 over the past year, and contact with people with confirmed COVID-19. Patients' medical records were reviewed to access data regarding disease and current medications. A qualitative immunochromatographic SARS-CoV-2 test was performed in all participants. All patients who were using rituximab or intravenous human immunoglobulin, or had symptoms of COVID-19, were excluded. Results. Patients' group included 11 (14.3%) JDM patients, 31 (40.2%) JIA, 25 (32.4%) JSLE, six patients with vasculitis, two with SS, one MCTD and one with autoinflammatory syndrome. Patients and controls were similar in terms of female gender (70.1% vs. 57.8%, p=0.173), median age (14 vs. 13 years, p=0.269) and SARS-CoV-2 serology positivity (22% vs. 15.5%, p=0.481). 80.5% of rheumatic patients were in use of immunosuppressive drugs, 27.3% of them using corticosteroids, 33.3% in high doses, and 7.8% on immunobiologicals. No statistical differences were found between positive (n=17) and negative serology (n=60) patients regarding demographic/socioeconomic data, contact with people with confirmed COVID-19, use and number of immunosuppressive drugs, use and dose of corticosteroids, use of hydroxychloroquine and immunobiological drugs (p>0.05). Regarding the profile of JDM patients, 6/11 (54%) were female, the median age was 13 years (range 9-17) and 3/11 (27%) presented COVID-19 serology positivity. 2/11 were in immunosuppressive treatment, however none of them were in use of glucocorticoids and biologic agents. Conclusions. Pediatric JDM and other rheumatic diseases patients were infected at the same rate as healthy ones. Neither the underlying pathology nor its treatment seemed to interfere with the contagion risk.
ABSTRACT
Background. Autoimmune rheumatic diseases (ARD) include various chronic conditions with high morbidity and mortality rates, and an increased risk of infections, including the new COVID-19. It is possible that adolescents with ARD have higher levels of psychological distress which may affect their mental health and life conditions. The objectives were to assess mental health and life conditions in adolescents with autoimmune rheumatic diseases (ARD) and healthy controls in social isolation, emphasizing some demographic aspects and daily routine of adolescents with juvenile dermatomyositis (JDM) during the COVID-19 quarantine. Methods. A cross-sectional study, performed from July 2020 to October 2020, included 155 ARD adolescents and 105 healthy controls. Online survey composed by self-reported strengths and difficulties questionnaire (SDQ) and a semi-structured questionnaire was filled in regarding demographic data, daily home and school routine, physical activities and COVID-19 information during the pandemic. Results. The patients included in the study presented the following underlying diseases: 15% JDM, 29% juvenile systemic lupus erythematosus (JSLE) and 56% juvenile idiopathic arthritis (JIA). Among adolescents with JDM, 71% were female, 54% Caucasian and the median age was 14 years (range 10-18). Regarding school data, 92% JDM participants attended school before pandemic, 75% studied in public schools and up to 17% did not present home schooling during the quarantine. All JDM patients agreed with stay-home policy after pandemic outbreak, and they reported change in life routine (96%), sleep problems (29%), sleep after midnight (75%) and increased screen time (87%). Worsening of family financial situation (37%) and increased family violence (8%) were also observed. Concerning mental health assessment, it was verified that one third of JDM subjects presented abnormal total difficulties and emotional scores of SDQ. No differences were found regarding sex, ethnicity and current age between ARD patients and controls (p>0.05). The frequencies of abnormal SDQ total (32% vs. 32%, p=0.901) and emotional (38% vs. 35%, p=0.653) were similar in both groups. Logistic regression analyses in ARD patients demonstrated that female (OR=2.4;95%CI 1.0-6.0;p=0.044) was associated with severe emotional SDQ dysfunction, whereas poor sleep quality was considered risk factor for both worse total SDQ (OR 2.6;95% CI 1.2-5.5;p=0.009) and emotional SDQ scores (OR=4.6;95%CI 2.2-9.7;p<0.001). Comparisons between ARD patients with and without current prednisone use showed higher median scores of peer problems in the first group [3(0-10) vs. 2(0-7), p=0.049]. The median and frequencies of SDQ scores and domains were similar between JDM, JSLE and JIA (p>0.05). Conclusions. Approximately one third of JDM, JSLE and JIA patients presented abnormal total difficulties and emotional scores of SDQ. Female sex and poor sleep quality were the main factor associated with emotional impact in these ARD adolescents.
ABSTRACT
Background: We recently reported an attenuate immunogenicity in patients with autoimmune rheumatic diseases. However, the effect of spondyloarthritis (SpA) and its treatment on COVID-19 vaccine immunogenicity remains to be determined for this group of patients. We therefore aimed to evaluate humoral immune responses to inactivated SARS-CoV-2 vaccine (CoronaVac) in patients with SpA (axial spondyloarthritis and psoriatic arthritis) taking DMARDs and commonly used targeted biological therapies, compared with a control group(CG). Objectives: Evaluate immunogenicity and safety of CORONAVAC (Sninovac, Beijing) in Spondyloarthritis (SpA) patients. Methods: Prospective observational cohort patients diagnosed with 194 SpA and 183 CG were vaccinated with CoronaVac in two doses with a 28-days interval. 194 patients completed the study and could be paired with CG for immunogenicity analysis. Blood samples were collected in the days 0, 28 and 69 (D69) to evaluate anti-SARS-CoV-2 IgG seroconversion(SC) and presence of neutralizing antibodies (NAb) in participants with negative IgG and NAb at baseline. Results: Patients and GC were comparable regarding age (p=0.93) and sex (p=1.00). Immunogenicity at D69 showed a moderate/high SC (80.2% vs. 95.7%, p<0.0001) and Nab positivity (61.6% vs. 82.7%, p<0.0001) in SpA but lower than CG. Factors associated with lower immunogenicity were older age (56.8 vs. 51.4;p=0.03318) and higher frequencies of prednisone (25.7% vs 4.2%;p=0.0004), methotrexate (51.4% vs 40.1%, p=0.0016) and TNF inhibitor (TNFi) (62.9% vs 34.5%, p=0.0035). Likewise, prednisone (17.6% vs. 2.8%, p=0.0013) and TNFi (50% vs 33.9%;p=0.0408) were associated with diminished NAb positivity. Sulfasalazine was associated with higher SC rates (8.6% vs. 26.8%, p=0.0246) and NAb positivity (13.2% vs. 29.4%, p=0.0168). The multivariate analysis revealed that older age (p=0.037), prednisone (p=0.001), TNFi (p=0.016), and methotrex-ate(p=0.017) were independently associated with lower SC while prednisone (p=0.006) and TNFi (p=0.027) were also associated with reduced NAb response. Conclusion: Our fnding of an excellent safety and moderate/high SC rate in SpA supports the recommendation of CoronaVac vaccination. The impaired immune response in the minority of patients under immunosuppressive and biological therapy requires novel strategies to enhance antibody response in this subgroup of patients.
ABSTRACT
Background: Patients with rheumatoid arthritis (RA) on methotrexate have reduced vaccine responses. Temporary discontinuation has improved immuno-genicity of anti-infuenza vaccine, but this strategy has not been evaluated in anti-SARS-CoV-2 vaccines. Objectives: To 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. Methods: This was a single-center, prospective, randomized, investigator-blinded, intervention study (#NCT04754698, CoronavRheum), including adult RA patients (stable CDAI≤10, prednisone ≤7.5mg/day), randomized (1:1) to withdraw MTX (MTX-hold) for 2 weeks after each vaccine dose or maintain MTX (MTX-maintain), evaluated at D0, D28 and D69. Co-primary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion(SC) and neutralizing antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titers (GMT) and fare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and, for safety reasons, those who fared at D28 (CDAI>10) and did not withdraw MTX twice. Results: Randomization 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: 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, MTX-hold (n=37) had a higher rate of seroconversion than MTX-maintain (n=55) group [29 (78.4%) vs 30 (54.5%), p=0.019], 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]. At D28 fare, rates were comparable in both groups (CDAI, p=0.122;DAS28-CRP, p=0.576), whereas CDAI>10 was more frequent in MTX-hold at D69 (p=0.024). Conclusion: We provide novel data that 2-week MTX withdrawal after each Sinovac-CoronaVac vaccine dose improves anti-SARS-CoV-2 IgG response. The increased fare rates after second MTX withdrawal may be attributed to the short-term interval between vaccine doses. This strategy requires close surveillance and shared decision making due to the possibility of fares.