ABSTRACT
The EULAR COVID-19 registry, launched in March 2020, is an observational registry that captures physician-entered data on both adult and paediatric patients with a pre-existing rheumatic and musculoskeletal disease (RMD) and SARSCoV-2 infection. Data are entered voluntarily directly into the European data entry portal. In addition, as some countries were already collecting COVID-19 data, either within existing registries or in new COVID-19 registries (France, Germany, Greece, Italy, Portugal, Sweden and Switzerland), they were invited to share their data with the EULAR COVID-19 registry. EULAR data are then merged with data from the Global Rheumatology Alliance (GRA) for analysis. The aim of the EULAR-GRA COVID-19 registry is to collect, analyze, generate and disseminate information about COVID-19 and rheumatology to patients, physicians and other relevant groups to improve the care of patients with rheumatic disease. Later during the pandemic, patients with immune-mediated inflammatory diseases (including inflammatory RMDs) were excluded from SARS-CoV-2 vaccine clinical development programmes;therefore, questions regarding the safety, effectiveness and potential measures that may increase the safety and effectiveness of vaccination against SARS-CoV-2 were unanswered. Lack of data led to some contradictory advice from rheumatology organisations and healthcare professionals regarding some of these vaccination aspects. In order to contribute to more informed decisions by patients and healthcare professionals and more robust and homogeneous evidence-based recommendations from relevant organisations, EULAR decided to create a second registry to collect data and learn about vaccination outcomes in people with RMDs. At the 4th Global Conference on Myositis (GCOM), myositis-specific data from these two registries will be presented.
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Anti-viral vaccination has rarely been associated with Guillain- Barre syndrome(GBS). We performed a population-based study of NHS England data and a UK multicentre surveillance study to investigate the relationship between COVID-19 vaccination and GBS. We linked GBS cases from England's National Immunoglobulin Database(NID) with COVID-19 vaccina- tion data from December 2020-July 2021. GBS temporally associated within a 6-week risk window of any COVID-19 vaccine was identified. We prospectively collected incident UK GBS cases January- November 2021 regardless of vaccine exposure. The NID recorded 996 English GBS cases January-October 2021. A spike of cases above the 2016-2020 average occurred March-April 2021. 198 cases occurred within 6 weeks of first-dose COVID-19 vaccina- tion (0.618cases/ 100,000vaccinations: 176 ChAdOx1 nCoV-19, 21 tozinameran, 1 mRNA-1273). First-dose ChAdOx1 nCoV-19 accounted for the excess of 98-140 GBS cases with a peak 24 days post-vaccination. First-dose tozinameran and seconddose any vaccination showed no excess GBS risk. The UK multicen- tre surveillance dataset (121 patients) identified no phenotypic or demographic differences between vaccinelinked and unlinked cases. First-dose ChAdOx1 nCoV-19 vaccination is associated with excess GBS risk 0.576 (95%CI 0.481-0.691) cases/100,000 doses. No specific features are associated with vaccinationrelated GBS cases. The mechanism of immunogenicity of ChAdOx1 nCoV-19- warrants further study.
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Objectives. To determine characteristics associated with a more severe COVID-19 outcome in people with Sjogren's disease (SJD). Methods. People with SJD and COVID-19 reported to two international registries (Sjogren Big Data Consortium and COVID-19 Global Rheumatology Alliance) from March 2020 to October 2021 were included. An ordinal COVID-19 severity scale was defined: (1) not hospitalized, (2) hospitalized with no ventilation, (3) hospitalized requiring non-invasive ventilation, (4) hospitalized requiring invasive ventilation, and (5) death. Odds ratios (OR) were estimated using a multivariable ordinal logistic regression model adjusted for age, sex, comorbidities and anti-rheumatic medications included as covariates. Results. A total of 898 people with SJD were included (825 (91.8%) women, mean age SARS-CoV-2 infection diagnosis: 55.5 years), including 652 patients with primary SJD and 246 with other associated systemic rheumatic diseases. 33.9% were hospitalized, 14.5% required ventilation, and 4.3% died. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.05), male sex (OR 1.81, 95% CI 1.10 to 2.92), two or more comorbidities (OR 2.99, 95% CI 1.92 to 4.67;vs none), baseline therapy with corticosteroids (OR 2.04, 95% CI 1.20 to 3.46), immunosuppressive agents (OR 2.09, 95% CI 1.30 to 3.38) and B-cell depleting agents (OR 5.38, 95% CI 2.77 to 10.47) were associated with worse outcomes (reference for all medications: hydroxychloroquine only). Conclusions. More severe COVID-19 outcomes in individuals with Sjogren's are largely driven by demographic factors and baseline comorbidities. Patients using immunosuppressants, especially rituximab, also experienced more severe outcomes.
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Background: Some factors associated with severe COVID-19 outcomes have been identifed in patients with psoriasis (PsO) and infammatory/autoimmune rheumatic diseases, namely older age, male sex, comorbidity burden, higher disease activity, and certain medications such as rituximab. However, information about specifcities of patients with PsO, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), including disease modifying anti-rheumatic drugs (DMARDs) specifcally licensed for these conditions, such as IL-17 inhibitors (IL-17i), IL-23/IL-12 + 23 inhibitors (IL-23/IL-12 + 23i), and apremilast, is lacking. Objectives: To determine characteristics associated with severe COVID-19 outcomes in people with PsO, PsA and axSpA. Methods: This study was a pooled analysis of data from two physician-reported registries: the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), comprising patients with PsO/PsA, and the COVID-19 Global Rheumatology Alliance (GRA) registry, comprising patients with PsA/axSpA. Data from the beginning of the pandemic up to 25 October, 2021 were included. An ordinal severity outcome was defned as: 1) not hospitalised, 2) hospitalised without death, and 3) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics (age, sex, time period of infection), comorbidities (hypertension, other cardiovascular disease [CVD], chronic obstructive lung disease [COPD], asthma, other chronic lung disease, chronic kidney disease, cancer, smoking, obesity, diabetes mellitus [DM]), rheumatic/skin disease (PsO, PsA, axSpA), physician-reported disease activity, and medication exposure (methotrexate, lefunomide, sulfasalazine, TNFi, IL17i, IL-23/IL-12 + 23i, Janus kinase inhibitors (JAKi), apremilast, glucocorticoids [GC] and NSAIDs). Age-adjustment was performed employing four-knot restricted cubic splines. Country-adjustment was performed using random effects. Results: A total of 5008 individuals with PsO (n=921), PsA (n=2263) and axSpA (n=1824) were included. Mean age was 50 years (SD 13.5) and 51.8% were male. Hospitalisation (without death) was observed in 14.6% of cases and 1.8% died. In the multivariable model, the following variables were associated with severe COVID-19 outcomes: older age (Figure 1), male sex (OR 1.53, 95%CI 1.29-1.82), CVD (hypertension alone: 1.26, 1.02-1.56;other CVD alone: 1.89, 1.22-2.94;vs no hypertension and no other CVD), COPD or asthma (1.75, 1.32-2.32), other lung disease (2.56, 1.66-3.97), chronic kidney disease (2.32, 1.50-3.59), obesity and DM (obesity alone: 1.36, 1.07-1.71;DM alone: 1.85, 1.39-2.47;obesity and DM: 1.89, 1.34-2.67;vs no obesity and no DM), higher disease activity and GC intake (remission/low disease activity and GC intake: 1.96, 1.36-2.82;moderate/severe disease activity and no GC intake: 1.35, 1.05-1.72;moderate/severe disease activity and GC intake 2.30, 1.41-3.74;vs remission/low disease activity and no GC intake). Conversely, the following variables were associated with less severe COVID-19 outcomes: time period after 15 June 2020 (16 June 2020-31 December 2020: 0.42, 0.34-0.51;1 January 2021 onwards: 0.52, 0.41-0.67;vs time period until 15 June 2020), a diagnosis of PsO (without arthritis) (0.49, 0.37-0.65;vs PsA), and exposure to TNFi (0.58, 0.45-0.75;vs no DMARDs), IL17i (0.63, 0.45-0.88;vs no DMARDs), IL-23/IL-12 + 23i (0.68, 0.46-0.997;vs no DMARDs) and NSAIDs (0.77, 0.60-0.98;vs no NSAIDs). Conclusion: More severe COVID-19 outcomes in PsO, PsA and axSpA are largely driven by demographic factors (age, sex), comorbidities, and active disease. None of the DMARDs typically used in PsO, PsA and axSpA, were associated with severe COVID-19 outcomes, including IL-17i, IL-23/IL-12 + 23i, JAKi and apremilast.
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Introduction: It remains unknown whether children and young people with rheumatic and musculoskeletal diseases (RMD) who acquire COVID-19 infection have a more severe COVID-19 course, due to either underlying disease or immunosuppressive treatments. Objectives: To describe outcomes among children and young people with underlying RMD who acquire COVID-19 infection. Methods: All children and young people <19 years of age with COVID-19 (presumptive or confirmed) reported to the EULAR COVID- 19 Database, which collects details regarding RMD diagnosis and treatment, COVID infection and outcomes, between 27 March 2020 and 9 April 2021 (cut-off date for this analysis) were included. Patient characteristics and COVID-19 outcomes are presented. Results: A total of 364 children and young people (age range 2-18 years;table) have been reported to the database from 17 countries;mostly France (N=71), Germany (N=71), Czechia (N=59), Spain (N= 50), Israel (N=60), and UK (N=25). Most patients had a diagnosis of juvenile idiopathic arthritis (JIA;N=244;67%). There were 20 (5%) hospitalisations and 1 death reported due to COVID-19. The most commonly reported symptoms were fever (40%) and cough (30%). Only 42 (12%) patients reported glucocorticoid use. Any DMARD therapy was used by 251 (69%) patients;161 (44%) were on csDMARDs, 119 (33%) on anti-TNF. 40% were in remission at time of COVID-19 infection, 28% in low, and 9% in moderate/high disease activity. Among those with hospitalisation data [N=290], patients on any DMARD therapy (cs/b/tsDMARDs) had similar odds for hospitalisation compared with those not on therapy, adjusted for age, sex, rheumatic disease, and disease severity (odds ratio 1.3;95% CI 0.3, 4.6). Conclusion: These initial data on outcomes of COVID-19 infection in paediatric RMDs are very reassuring, only one-in-twenty patients were reported to be hospitalised. Due to the database design and inherent reporting bias, this is likely an overestimate, suggesting that overall outcomes among this population appear to be generally good, with mild infection. Increasing case reports to the database will allow further exploration of drug- and disease-specific outcomes.
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Background: The consequences of the COVID-19 outbreak are unprecedented and have been felt by everyone around the world, including people with rheumatic and musculoskeletal diseases (RMDs). With the development of vaccines, the future is becoming brighter. Vaccines are a key pillar of public health and have been proven to prevent many serious diseases. However, vaccination also raises questions, especially for patients with inflammatory RMDs and/or treated with drugs that influence their immune system. Objectives: Our aim was to collect safety data among RMD patients receiving COVID-19 vaccines. Methods: The EULAR COVID-19 Vaccination (COVAX) Registry is an observational registry launched on 5 February 2021. Data are entered voluntarily by clinicians or associated healthcare staff;patients are eligible for inclusion if they have an RMD and have been vaccinated against SARS-CoV-2. Descriptive statistics are presented. Results: As of 27 April 2021, 1519 patients were reported to the registry. The majority were female (68%) and above the age of 60 (57%). Mean age was 63 years (SD 16), ranging from 15 to 97 years. A total of 28 countries contributed to the registry, with France (60%) and Italy (13%) as the highest contributors. The majority (91%) had inflammatory RMDs. Inflammatory joint diseases accounted for 51% of cases, connective tissue diseases 19%, vasculitis 16%, other immune mediated inflammatory diseases 4%, and non-inflammatory/mechanical RMDs 9%. The most frequent individual diagnoses were rheumatoid arthritis (30%), axial spondyloarthritis (8%), psoriatic arthritis (8%), systemic lupus erythematosus (SLE, 7%) and polymyalgia rheumatica (6%). At the time of vaccination, 45% were taking conventional synthetic DMARDs, 36% biological DMARDs, 31% systemic glucocorticoids, 6% other immunosuppressants (azathioprine;mycophenolate;cyclosporine;cyclophosphamide;tacrolimus), and 3% targeted synthetic DMARDs. The most frequent individual DMARDs were methotrexate (29%), TNF-inhibitors (18%), antimalarials (10%) and rituximab (6%). The vaccines administered were: 78% Pfizer, 16% AstraZeneca, 5% Moderna and 1% other/unknown;66% of cases received two doses and 34% one dose. Mean time from 1st and 2nd dose to case report was 41 days (SD 26) and 26 days (SD 23), respectively. COVID-19 diagnosis after vaccination was reported in 1% (18/1519) of cases. Mean time from first vaccination until COVID-19 diagnosis was 24 days (SD 17). Disease flares were reported by 5% (73/1375) of patients with inflammatory RMDs, with 1.2% (17/1375) classified as severe flares. Mean time from closest vaccination date to inflammatory RMD flare was 5 days (SD 5). The most common flare types were arthritis (35/1375=2.5%), arthralgia (29/1375=2.1%), cutaneous flare (11/1375=0.8%) and increase in fatigue (11/1375=0.8%). Potential vaccine side effects were reported by 31% of patients (467/1519). The majority were typical early adverse events within 7 days of vaccination, namely pain at the site of injection (281/1519=19%), fatigue (171/1519=11%) and headache (103/1519=7%). Organ/system adverse events were reported by 2% (33/1519) but only 0.1% (2/1519) reported severe adverse events, namely a case of hemiparesis in a patient with systemic sclerosis/ SLE overlap syndrome (ongoing at the time of reporting), and a case of giant cell arteritis in a patient with osteoarthritis (recovered/resolved without sequelae). Conclusion: The safety profiles for COVID-19 vaccines in RMD patients was reassuring. Most adverse events were the same as in the general population, they were non-serious and involved short term local and systemic symptoms. The overwhelming majority of patients tolerated their vaccination well with rare reports of inflammatory RMD flare (5%;1.2% severe) and very rare reports of severe adverse events (0.1%). These initial findings should provide reassurance to rheumatologists and vaccine recipients, and promote confidence in COVID-19 vaccine safety in RMD patients, namely those with inflammatory RMDs and/or taking treatments that influence their immune system.
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Background: The severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) pandemic is a global health problem. Beside the specific pathogenic effect of SARS-CoV-2, incompletely understood deleterious and aberrant host immune responses play critical roles in severe disease. Rheumatologists have the best experience of studying and treating these complicated hyperinflammatory processes. Objectives: To summarize the available information on pathophysiology of COVID-19. Methods: As part of a EULAR taskforce, two systematic literature reviews were performed one on pathophysiology and one on immunomodulatory therapies. Two reviewers independently identified eligible studies according to the following PICO framework: P (population): patients with SARS-CoV-2 infection;I (intervention): any intervention/no intervention;C (comparator): any comparator;O (outcome) any clinical or serological outcome including but not limited to immune cell phenotype and function and serum cytokine concentration. The results pertaining to pathophysiology of COVID-19 are presented here. Results: Of the 55496 records yielded, 85 articles were eligible for inclusion. Included studies were at variable risk of bias and exploring various aspects of disease pathogenesis from immune to non-immune cells (Table 1). Pro-inflammatory cytokines' expression including IL-6, was increased, especially in severe COVID-19, although not as high as other states with severe systemic inflammation. Innate and adaptative immune cell compartments were differentially affected by SARS-CoV-2 infection: neutrophils displayed an immature differentiation state and also increased neutrophil extracellular traps (NETs) formation. Dendritic cell number was reduced and classical monocytes was increased although displaying a reduced expression of HLA-DR. The lymphoid compartment was also affected: lymphopenia was present with a reduced number of CD4+ and CD8+ T lymphocytes and more frequent PD1+CD8+ T cells corresponding to an exhausted phenotype. Antibody response to SARS-CoV-2 infection showed a high variability across individuals and disease spectrum. Multiparametric algorithms showed variable diagnostic performances in predicting survival, hospitalization, disease progression or severity, and mortality. Differences in SARS-CoV-2 manifestations in adults and children were highlighted. Conclusion: Overall, SARS-CoV-2 infection affects both innate and adaptative immune responses in a variable way, according to both disease severity and individual parameters. This SLR informs the EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19.
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Background: The COVID-19 pandemic has disrupted healthcare delivery and education of physicians, including rheumatology trainees. Objectives: To assess the impact of the COVID-19 pandemic on the clinical experiences, research opportunities, and well-being of rheumatology trainees. Methods: A voluntary, anonymous, web-based survey was administered in English, Spanish, or French from 19/08/2020 to 05/10/2020. Adult and paediatric rheumatology trainees worldwide in training in 2020 were invited to participate via social media and email. Using multiple choice questions, Likert scales, and free text answers, we assessed trainee patient care activities, redeployment, research, and well-being. Results: The 302 respondents were from 33 countries, with most (83%, 252/302) in adult rheumatology training. Many trainees (45%, 135/300) reported an increase in non-rheumatology clinical work (e.g. care of COVID-19 patients), with 52% of these (70/135) also continuing rheumatology clinical work. COVID-19 redeployment was not optional for 68% (91/134). Trainees reported a negative impact of the pandemic in their growth in rheumatology (Figure 1). They also reported a substantial impact on several training areas: outpatient clinics (79%, 238/302), inpatient consultations (59%, 177/302), formal teaching (55%, 167/302), procedures (53%, 147/302), teaching opportunities (52%, 157/302), and ultrasonography (36%, 110/302), with 87-96% perceiving a negative impact on these areas. Only 54% (159/294) reported feeling comfortable with their level of clinical supervision during the pandemic (Figure 1). Many trainees (46%, 128/280) reported changes in research experiences during the pandemic;39% (110/285) reported that COVID-19 negatively affected their ability to continue their pre-pandemic research and 50% (142/285) reported difficulty maintaining research goals (Figure 1). Some rheumatology trainees reported having health condition(s) putting them at high risk for COVID-19 (10%, 30/302) and 14% of trainees (41/302) reported having had COVID-19 (Table 1). Only 53% (160/302) reported feeling physically safe in the workplace while 25% (76/302) reported not feeling physically safe;reasons included lack of training about COVID-19, lack of comfort in the clinical setting, insufficient personal protective equipment, immunocompromised state, and pregnancy. Half (151/302) reported burnout and 68% (204/302) an increase in stress from work during the pandemic (Figure 1), whilst 25% (75/302) reported that changes to their training programme negatively impacted their physical health. Conclusion: The COVID-19 pandemic has negatively impacted the experience of rheumatology training as well as the well-being of trainees globally. Our data highlight concerns for rheumatology trainees including research opportunities and clinical care which should be a focus for curriculum planning.
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Background: The COVID-19 pandemic led to a rapid increase in remote consultations in rheumatology care. Due to the potential impact of this change on rheumatology clinical training, we investigated trainees' experiences with telemedicine. Objectives: To assess the impact of telemedicine use during the COVID-19 pandemic on rheumatology training, including supervision. Methods: A voluntary, anonymous web-based survey was administered in English, Spanish, or French from 19/08/2020 to 05/10/2020. Adult and paediatric rheumatology trainees worldwide in training in 2020 were invited to participate via social media and email. Using multiple choice questions, Likert scales, and free text answers, we collected data regarding prior and current telemedicine use, training, and supervision. Results: 302 respondents from 33 countries completed the survey, with most (83%, 252/302) in adult rheumatology training. Reported use of telemedicine increased from 13% (39/302) pre-pandemic to 82% (247/302) (Table 1). European trainees predominantly utilised audio-only compared to trainees from the rest of the world (ROW) who predominantly utilised audio-video telemedicine. Most trainees continued to evaluate new patients using telemedicine (65%, 161/247). A larger proportion of trainees were comfortable using telemedicine to evaluate follow-up (69% 170/247) versus new patients (25%, 41/161) (Figure 1). Only 32% (97/302) were trained in telemedicine, with the highest proportion among United States (US) trainees (59%, 69/116);subjects included software, clinical skills, and billing. The majority of trainees found this helpful (92%, 89/97). Supervision was most frequently in the form of verbal discussion after the consultation (Table 1);24% (59/247) had no telemedicine supervision during the pandemic. In general, trainees found telemedicine negatively impacted their supervision (51%, 123/242) and clinical teaching quality (70%, 171/244);only 9% reported a positive impact on these areas. Conclusion: Adoption of telemedicine during the COVID-19 pandemic has led to areas of concern for rheumatology trainees including inadequate supervision and clinical teaching. Our results suggest a need for education on evaluation of new patients using telemedicine, increasing telemedicine training, and ensuring adequate supervisory arrangements.