Characteristics and outcomes of SARS-CoV-2 breakthrough infections among double-vaccinated and triple-vaccinated patients with inflammatory rheumatic diseases.

OBJECTIVE: To analyse the clinical profile of SARS-CoV-2 breakthrough infections in at least double-vaccinated patients with inflammatory rheumatic diseases (IRDs). METHODS: Data from the physician-reported German COVID-19-IRD registry collected between February 2021 and July 2022 were analysed. SARS-CoV-2 cases were stratified according to patients' vaccination status as being not vaccinated, double-vaccinated or triple-vaccinated prior to SARS-CoV-2 infection and descriptively compared. Independent associations between demographic and disease features and outcome of breakthrough infections were estimated by multivariable logistic regression. RESULTS: In total, 2314 cases were included in the analysis (unvaccinated n=923, double-vaccinated n=551, triple-vaccinated n=803, quadruple-vaccinated n=37). SARS-CoV-2 infections occurred after a median of 151 (range 14-347) days in patients being double-vaccinated, and after 88 (range 14-270) days in those with a third vaccination. Hospitalisation was required in 15% of unvaccinated, 8% of double-vaccinated and 3% of triple-vaccinated/quadruple-vaccinated patients (p<0.001). Mortality was 2% in unvaccinated, 1.8% in the double-vaccinated and 0.6% in triple-vaccinated patients. Compared with unvaccinated patients, double-vaccinated (OR 0.43, 95% CI 0.29 to 0.62) and triple-vaccinated (OR 0.13, 95% CI 0.08 to 0.21) patients showed a significant lower risk of COVID-19-related hospitalisation. Using multivariable analysis, the third vaccination was significantly associated with a lower risk for COVID-19-related death (OR 0.26; 95% CI 0.01 to 0.73). CONCLUSIONS: Our cross-sectional data of COVID-19 infections in patients with IRD showed a significant reduction of hospitalisation due to infection in double-vaccinated or triple-vaccinated patients compared with those without vaccination and even a significant reduction of COVID-19-related deaths in triple-vaccinated patients. These data strongly support the beneficial effect of COVID-19 vaccination in patients with IRD. TRIAL REGISTRATION NUMBER: EuDRACT 2020-001958-21.

Environmental and societal factors associated with COVID-19-related death in people with rheumatic disease: an observational study.

Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally. Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death. Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 µg/m3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p<0·0001), and population mobility (1·03 per 1% increase in number of visits to grocery and pharmacy stores [1·02-1·05]; p<0·0001 and 1·02 per 1% increase in number of visits to workplaces [1·00-1·03]; p=0·032) were independently associated with higher odds of mortality. Number of hospital beds (0·94 per 1-unit increase per 1000 people [0·88-1·00]; p=0·046), human development index (0·65 per 0·1-unit increase [0·44-0·96]; p=0·032), government response stringency (0·83 per 10-unit increase in containment index [0·74-0·93]; p=0·0018), as well as follow-up time (0·78 per month [0·69-0·88]; p<0·0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1·2% [0·1-9·5]; p=0·14). Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities. Funding: American College of Rheumatology and European Alliance of Associations for Rheumatology.

Do patients with rheumatoid arthritis show a different course of COVID-19 compared to patients with spondyloarthritis?

OBJECTIVES: Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are the most common inflammatory rheumatic diseases (IRD). The aim of this study was to elucidate differences in the outcome of SARS-CoV-2 infection in RA- and SpA-patients. METHODS: Data from the German COVID-19 registry for IRD patients from 30th March to 16th November 2020 were analysed. 208 RA and SpA patients were included in the study, matched for gender and age. RESULTS: 104 SpA patients (40% patients with ankylosing spondylitis, 54% with psoriatic arthritis and 6% with enteropathic arthritis) were compared to 104 RA patients. For both groups, median age was 56 years. TNF-i treatment was reported in 45% of the SpA and in 19% of RA patients (p=0.001). Glucocorticoids were used in 13% of the SpA and in 40% of the RA patients (p=0.001). In both groups, the majority of the patients (97% SpA, 95% RA) recovered from COVID-19. Hospitalisation was needed in 16% of the SpA and in 30% of the RA patients (p=0.05), and oxygen treatment in 10% and 18% respectively (p=ns). Three versus six (p=ns) fatal courses were reported in the SpA versus the RA group. CONCLUSIONS: The study revealed that the hospitalisation rate during COVID-19 infection, but not the mortality, was significantly higher in RA as compared to SpA patients. This could be explained either by different treatment strategies or by different susceptibilities of the two diseases.

Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry: a retrospective cohort study.

BACKGROUND: Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. METHODS: In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behçet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. FINDINGS: Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behçet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31-1·57]), were male compared with female (1·38 [1·05-1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23-1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50-3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49-3·02]). Risk factors varied among different disease subtypes. INTERPRETATION: Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. FUNDING: American College of Rheumatology and the European Alliance of Associations for Rheumatology.

A survey to evaluate knowledge, perceptions and attitudes toward COVID-19 vaccinations among rheumatologists in Germany.

The objective is to evaluate the attitude of rheumatologists regarding the use of COVID-19 vaccination in patients with inflammatory rheumatic diseases (IRDs). From February 2nd until March 15th, 2021, rheumatologists from Germany were asked to participate anonymously in a survey addressing their attitude with respect to COVID-19 vaccinations of IRD patients. The survey was completed by 214 participants (107 men, 103 women, 4 unspecified). More than half of the physicians (61%) were working in rheumatologic private practices and 62% had more than 20 years of experience in rheumatology. 90% reported to be at least confidential in handling issues of COVID-19 vaccination and 99% would recommend COVID-19 vaccination for IRD patients. The majority would not recommend to stop or reduce immunomodulatory drugs for vaccination except for rituximab. More than 70% would prefer vaccination with a mRNA vaccine for their IRD patients. This study shows that almost all rheumatologists in Germany support the COVID-19 vaccination for their IRD patients without reducing or terminating the actual immunomodulatory medication to potentially improve the response to the vaccine. This attitude is in accordance with the current recommendations of the German Society of Rheumatology regarding COVID-19 vaccination in IRD patients, and indicates that these have been well accepted and work in everyday clinical practice.

[German registry www.Covid19-Rheuma.de : Status report after 1 year of the pandemic]. / Deutsches Register www.Covid19-Rheuma.de : Statusbericht nach 1 Jahr der Pandemie.

The COVID-19 registry ( www.covid19-rheuma.de ) of the German Society of Rheumatology was the first registry for the acquisition and systemic evaluation of viral infections in patients with inflammatory rheumatic diseases (IRD). This has enabled rapid generation of scientific data that will help to improve the care of patients with IRD in the context of the pandemic. In addition to confirming general risk factors, such as patient age and comorbidities (e.g. cardiovascular, chronic lung and kidney diseases), the use of glucocorticoids and the disease activity of the rheumatic disease could be identified as disease-specific independent risk factors for the need of hospitalization due to COVID-19. Evaluations of the continuously growing cohort of patients with IRD and COVID-19 enable recommendations for patient care to be based on better evidence. Cooperation with international rheumatology registries (e.g. European COVID-19 registry for IRD) enables analyses of aggregated cohorts of patients with IRD and COVID-19 for international comparisons and statistically even more reliable statements.

Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry.

OBJECTIVE: To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA). METHODS: We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders. RESULTS: Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity. CONCLUSIONS: People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

The Key Comorbidities in Patients with Rheumatoid Arthritis: A Narrative Review.

Comorbidities in patients with rheumatoid arthritis (RA) are often associated with poor health outcomes and increased mortality. Treatment decisions should take into account these comorbidities due to known or suspected associations with certain drug classes. In clinical practice, it is critical to balance potential treatment benefit against the possible risks for comorbidities as well as the articular manifestations of RA. This review summarises the current literature relating to prevalence and risk factors for the important comorbidities of cardiovascular disease, infections, lymphomas and nonmelanoma skin cancers in patients with RA. The impact on patient outcomes and the interplay between these comorbidities and the therapeutic options currently available, including tumour necrosis factor inhibitors and newer biological therapies, are also explored. As newer RA therapies are developed, and patients gain wider and earlier access to advanced therapies, in part due to the emergence of biosimilars, it is important to consider the prevention or treatment of comorbidities as part of the overall management of RA.

The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET.

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.

Case report of severe PCR-confirmed COVID-19 myocarditis in a European patient manifesting in mid January 2020.

BACKGROUND: Viral genesis is the most common cause of myocarditis. COVID-19-associated myocarditis seems to be a notable extrapulmonary manifestation, which may result in the need for a different treatment. There has been no positive polymerase chain reaction (PCR) testing of SARS-CoV-2 in heart specimens, thus far. CASE SUMMARY: A 48-year-old male patient presented with fever, dyspnoea, and haemoptysis. Laboratory findings showed highly elevated inflammatory and cardiac damage markers. Thoracic computed tomography (CT) revealed bilateral, patchy peripheral ground-glass opacities with a crazy-paving pattern, focal consolidations, and mild pleural effusions. Cardiac imaging with echocardiography and magnetic resonance imaging (MRI) detected a reduced biventricular function. MRI additionally showed myocardial oedema and late gadolinium enhancement. Lung and heart biopsies were performed, revealing alveolitis with necrosis and acute lymphocytic myocarditis. Testing for usual cardiotropic viruses was negative, and no aspects of vasculitis or granuloma could be found. Due to fulfilling the criteria, the patient was diagnosed with rheumatic vasculitis. Treatment with cyclophosphamide and steroids was initiated. Later, the patient reported a history of travel to Tyrol in mid January. Consequently, PCR testing for SARS-CoV-2 was performed, which was positive in the heart specimen. Immunosuppressive treatment was discontinued. During a follow-up visit at the end of April, the patient's recovery was stable. DISCUSSION: In COVID-19 infections, myocardial inflammation can be present as an extrapulmonary manifestation. Positive PCR testing confirms myocardial invasion of the virus. Imaging and laboratory studies correlate with the histopathological findings, and thus should be performed in COVID-19 patients who are suspicious for myocarditis. Supportive treatment with steroids may be useful in these patients.