High prevalence of radiographic erosions in early, untreated PsA: results from the SpARRO cohort.

AIMS: To investigate the prevalence and distribution of bone erosions in an early psoriatic arthritis (PsA) population using conventional radiography (CR) and to explore the agreement between CR and ultrasound (US) detected bone erosions. METHODS: Newly diagnosed, treatment naïve PsA patients fulfilling the ClASsification for Psoriatic Arthritis (CASPAR) classification criteria of ≤5 years symptom duration were recruited as part of the Leeds Spondyloarthropathy Register for Research and Observation and underwent CR and US examination of hands and feet. RESULTS: Overall, 4655 hand and feet joints were assessed in 122 patients. CR erosions were detected in 24.6% (n=30) with lowest prevalence seen below 8 months of symptoms (17.5% vs 24.3%>24 months). The number of erosions was higher on CR (1.55% (63/4,655); US 1.04% (34/3,270)), with 5th metatarsophalangeal (MTP) joint being the most affected site in both CR (5.21% (11/211)) and US (7.14% (15/210)). Erosions in CR were more evenly distributed compared with US where three-quarters of the total number of bone erosions were detected in wrists, second metacarpophalangeal (MCP) and fifth MTP joints. Most joints had almost perfect prevalence-adjusted bias-adjusted kappa values ranging from 0.91 to 1. CONCLUSIONS: Erosions were seen in a quarter of patients with newly diagnosed, untreated PsA with a declining trend around the 8-month symptom duration cut-off. High levels of agreement between CR and US were seen with CR detecting more erosions. A focused US assessment of the wrist, second MCP and fifth MTP joints may be useful to detect bone erosions in early PsA.

Collating the voice of people with autoimmune diseases: Methodology for the Third Phase of the COVAD Studies.

INTRODUCTION: The growing recognition of holistic patient care highlights the various factors shaping the quality of life of individuals with autoimmune and rheumatic diseases (AIRDs). Beyond the traditional disease measures, there is an emerging acknowledgment of the less-explored aspects, including subjective well-being, social determinants of health, comorbidities, mental health, and medication adherence. Moreover, digital health services have empowered patients to engage actively in decision-making alongside clinicians. To explore these domains within the context of AIRDs, the "Collating the Voice of People with Autoimmune Diseases" COVAD survey was conceived, a successor of the previous two COVAD surveys. In this document, we present the study protocol in comprehensive detail. METHODS: The COVAD-3 survey is a cross-sectional patient self-reported e-survey incorporating multiple widely accepted scales/scores to assess various aspects of patients' lifestyles objectively. To ensure the survey's accuracy and usability across diverse regions, it will be translated into multiple languages and subjected to rigorous vetting and pilot testing. It will be distributed by collaborators via online platforms and data will be collected from patients with AIRDs, and healthy individuals over eight months. Data analysis will focus on outcome measures related to various social, demographic, economic, and psychological factors. CONCLUSION: With the increasing awareness to adopt a holistic treatment approach encompassing all avenues of life, the COVAD-3 survey aims to gain valuable insights into the impact of social, demographic, economic, and psychological determinants of health on the subjective well-being in patients with AIRDs, which will contribute to a better understanding of their overall health and well-being.

Impaired health-related quality of life in idiopathic inflammatory myopathies: a cross-sectional analysis from the COVAD-2 e-survey.

Objectives: To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Methods: Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. Results: We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10-15] IIMs vs 13 [11-15] non-IIM AIRDs vs 15 [13-17] nrAIDs vs 17 [15-18] controls, P < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10-15) IIMs vs 15 (13-17) controls, P < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Conclusion: Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs.

Breakthrough SARS-CoV-2 infection and disease flares in patients with rheumatoid arthritis: result from COVAD e-survey study.

COVID-19 has been suggested as a possible trigger of disease flares in patients with rheumatoid arthritis (RA). However, factors associated with disease flares remain unknown. This study aimed to identify factors associated with breakthrough infection (BIs) and disease flares in patients with RA following COVID-19. We analysed data from RA patients who participated in the COVID-19 vaccination in autoimmune diseases (COVAD) study. Demographic data, patient-reported outcomes, comorbidities, pharmacologic treatment and details regarding disease flares were extracted from the COVAD database. Factors associated with disease flare-ups were determined by multivariate logistic regression analysis. The analysis comprised 1928 patients with RA who participated in the COVAD study. Younger age, Caucasian ethnicity, comorbidities with obstructive chronic pulmonary disease and asthma were associated with COVID-19 breakthrough infection. Moreover, younger age (odds ratio (OR): 0.98, 95% CI 0.96-0.99, p < 0.001), ethnicity other than Asian, past history of tuberculosis (OR: 3.80, 95% CI 1.12-12.94, p = 0.033), treatment with methotrexate (OR: 2.55, 95% CI: 1.56-4.17, p < 0.001), poor global physical health (OR: 1.07, 95% CI 1.00-1.15, p = 0.044) and mental health (OR: 0.91, 95% CI 0.87-0.95, p < 0.001) were independent factors associated disease flares in patients with RA. Our study highlights the impact of socio-demographic factors, clinical characteristics and mental health on disease flares in patients with RA. These insights may help determine relevant strategies to proactively manage RA patients at risk of flares.

Characteristics and risk factors of COVID-19 breakthrough infections in Idiopathic Inflammatory Myopathies: Results from the COVAD study.

OBJECTIVES: To explore prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIM) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. METHODS: A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after 2 vaccine doses. We compared BIs characteristics and severity among IIMs, other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HC). Multivariable Cox regression models assessed the risk factors for BI, severe BI and hospitalisations among IIMs. RESULTS: Among 9449 included response, BIs occurred in 1447 (15.3%) respondents, median age 44 years (IQR 21), 77.4% female, and 182 BIs (12.9%) occurred among 1406 IIMs. Multivariable Cox regression among IIMs showed age as a protective factor for BIs [Hazard Ratio (HR)=0.98, 95%CI = 0.97-0.99], hydroxychloroquine and sulfasalazine use were risk factors (HR = 1.81, 95%CI = 1.24-2.64, and HR = 3.79, 95%CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for severe BI (HR = 3.61, 95%CI = 1.09-11.8). Non-White ethnicity (HR = 2.61, 95%CI = 1.03-6.59) was a risk factor for hospitalisation. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIM = 6.0% vs AIRD = 1.8%, nrAID = 2.2%, and HC = 0.9%), intensive care unit admission (IIM = 2.2% vs AIRD = 0.6%, nrAID, and HC = 0%), advanced treatment with antiviral or monoclonal antibodies (IIM = 34.1% vs AIRD = 25.8%, nrAID = 14.6%, and HC = 12.8%), and had more hospitalisation (IIM = 7.7% vs AIRD = 4.6%, nrAID = 1.1%, and HC = 1.5%). CONCLUSION: Patients with IIMs are susceptible to severe COVID-19 BI. Age and immunosuppressive treatments were related to the risk of BIs.

Novel Targeted Therapies for Rheumatoid Arthritis Based on Intracellular Signalling and Immunometabolic Changes: A Narrative Review.

Rheumatoid arthritis (RA) is a relatively common systemic autoimmune disease with an estimated prevalence of approximately 1% worldwide. Patients present predominantly with symmetrical small joint inflammatory arthritis, which involves dysregulated immune responses, leading to bone and cartilage deformities due to extensive erosive damage. The introduction of biological based therapies for the management of this life-altering condition, over the past three decades, has led to marked improvements in patients' quality of life. A wide range of both innate and adaptive immune cells are involved in the pathogenesis of RA, with a complex interplay of cytokines, T-cells, B-cells, and dendritic cells. Some of these cells have been successfully targeted in the treatment of RA by the use of biologics-based therapies. For example, rituximab therapy blocks B cell activation and abatacept effectively blocks T cell activation in patients with RA. Despite these advances, there remain some patients who are resistant to all current therapeutic options, which has encouraged further research into understanding the primary signal transduction pathways that mediate the disease. In this review we discuss the roles of the main signalling pathways, including metabolic reprogramming that have been implicated in RA disease progression, in order to develop a conceptual framework for more precise deployment of existing therapies, and to provide a rationale for producing molecular inhibitors of these pathways. Improved knowledge of the many intracellular signalling pathways in RA will complement current precision medicine strategies, particularly for the patients with difficult-to-treat RA, and especially in those with multidrug resistance disease.

Flares in IIMs and the timeline following COVID-19 vaccination: a combined analysis of the COVAD-1 and -2 surveys.

OBJECTIVES: Disease flares in the post-coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). METHODS: The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models. RESULTS: Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7-235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P < 0.001) were associated with disparity between self-reported and IS-denoted flares. CONCLUSION: A diagnosis of IIMs confers an equal risk of flares in the post-COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration.

Global disparities in the treatment of idiopathic inflammatory myopathies: results from an international online survey study.

OBJECTIVES: We aimed to explore current practice and interregional differences in the treatment of idiopathic inflammatory myopathies (IIMs). We triangulated these observations considering countries' gross national income (GNI), disease subtypes, and symptoms using patient-reported information. METHODS: A cross-sectional ancillary analysis of the 'COVID-19 vaccination in auto-immune disease' (COVAD) e-survey containing demographic characteristics, IIM subtypes (DM, PM, IBM, anti-synthetase syndrome [ASSD], immune-mediated necrotizing myopathy [IMNM], overlap myopathies [OM]), current symptoms (surrogate for organ involvement) and treatments (corticosteroids [CS], immunomodulators [IM], i.e. antimalarials, immunosuppressants [IS], IVIG, biologic treatments and targeted-synthetic small molecules). Treatments were presented descriptively according to continents, GNI, IIM and organ involvement, and associated factors were analysed using multivariable binary logistic regressions. RESULTS: Of 18 851 respondents from 94 countries, 1418 with IIM were analysed (age 61 years, 62.5% females). DM (32.4%), IBM (24.5%) and OM (15.8%) were the most common subtypes. Treatment categories included IS (49.4%), CS (38.5%), IM (13.8%) and IVIG (9.4%). Notably, treatments varied across regions, GNI categories (IS mostly used in higher-middle income, IM in lower-middle income, IVIG and biologics largely limited to high-income countries), IIM subtypes (IS and CS associated with ASSD, IM with OM and DM, IVIG with IMNM, and biologic treatments with OM and ASSD) and disease manifestations (IS and CS with dyspnoea). Most inter-regional treatment disparities persisted after multivariable analysis. CONCLUSION: We identified marked regional treatment disparities in a global cohort of IIM. These observations highlight the need for international consensus-driven management guidelines considering patient-centred care and available resources.

Type 1 diabetes, COVID-19 vaccines and short-term safety: Subgroup analysis from the global COVAD study.

AIMS/INTRODUCTION: Coronavirus disease 2019 (COVID-19) vaccinations have been proven to be generally safe in healthy populations. However, the data on vaccine safety in patients with type 1 diabetes are scarce. This study aimed to evaluate the frequency and severity of short-term (<7-day) adverse vaccination events (AEs) and their risk factors among type 1 diabetes patients. MATERIALS AND METHODS: This study analyzed data from the COVID-19 vaccination in Autoimmune Diseases (COVAD) survey database (May to December 2021; 110 collaborators, 94 countries), comparing <7-day COVID-19 vaccine AE among type 1 diabetes patients and healthy controls (HCs). Descriptive statistics; propensity score matching (1:4) using the variables age, sex and ethnicity; and multivariate analyses were carried out. RESULTS: This study analyzed 5,480 completed survey responses. Of all responses, 5,408 were HCs, 72 were type 1 diabetes patients (43 females, 48.0% white European ancestry) and Pfizer was the most administered vaccine (39%). A total of 4,052 (73.9%) respondents had received two vaccine doses. Patients with type 1 diabetes had a comparable risk of injection site pain, minor and major vaccine AEs, as well as associated hospitalizations to HCs. However, type 1 diabetes patients had a higher risk of severe rashes (3% vs 0.4%, OR 8.0, 95% confidence interval 1.7-36), P = 0.007), although reassuringly, these were rare (n = 2 among type 1 diabetes patients). CONCLUSIONS: COVID-19 vaccination was safe and well tolerated in patients with type 1 diabetes with similar AE profiles compared with HCs, although severe rashes were more common in type 1 diabetes patients.

COVID-19 breakthrough infections in type 1 diabetes mellitus: a cross-sectional study by the COVID-19 Vaccination in Autoimmune Diseases (COVAD) Group.

To investigate the frequency, profile, and severity of COVID-19 breakthrough infections (BI) in patients with type I diabetes mellitus (T1DM) compared to healthy controls (HC) after vaccination. The second COVID-19 Vaccination in Autoimmune Diseases (COVAD-2) survey is a multinational cross-sectional electronic survey which has collected data on patients suffering from various autoimmune diseases including T1DM. We performed a subgroup analysis on this cohort to investigate COVID-19 BI characteristics in patients with T1DM. Logistic regression with propensity score matching analysis was performed. A total of 9595 individuals were included in the analysis, with 100 patients having T1DM. Among the fully vaccinated cohort, 16 (16%) T1DM patients had one BI and 2 (2%) had two BIs. No morbidities or deaths were reported, except for one patient who required hospitalization with oxygen without admission to intensive care. The frequency, clinical features, and severity of BIs were not significantly different between T1DM patients and HCs after adjustment for confounding factors. Our study did not show any statistically significant differences in the frequency, symptoms, duration, or critical care requirements between T1DM and HCs after COVID-19 vaccination. Further research is needed to identify factors associated with inadequate vaccine response in patients with BIs, especially in patients with autoimmune diseases.

Correlates of breakthrough COVID-19 in vaccinated patients with systemic sclerosis: survival analysis from a multicentre international patient-reported survey.

This study aimed to assess the incidence, predictors, and outcomes of breakthrough infection (BI) following coronavirus disease (COVID-19) vaccination in patients with systemic sclerosis (SSc), a risk group associated with an immune-suppressed state and high cardiopulmonary disease burden. Cross-sectional data from fully vaccinated respondents with SSc, non-SSc autoimmune rheumatic diseases (AIRDs), and healthy controls (HCs) were extracted from the COVAD database, an international self-reported online survey. BI was defined according to the Centre for Disease Control definition. Infection-free survival was compared between the groups using Kaplan-Meier curves with log-rank tests. Cox proportional regression was used to assess the association between BI and age, sex, ethnicity, and immunosuppressive drugs at the time of vaccination. The severity of BI in terms of hospitalization and requirement for oxygen supplementation was compared between groups. Of 10,900 respondents, 6836 fulfilled the following inclusion criteria: 427 SSc, 2934 other AIRDs, and 3475 HCs. BI were reported in 6.3% of SSc, 6.9% of non-SSc AIRD, and 16.1% of HCs during a median follow-up of 100 (IQR: 60-137) days. SSc had a lower risk for BI than HC [hazard ratio (HR): 0.56 (95% CI 0.46-0.74)]. BIs were associated with age [HR: 0.98 (0.97-0.98)] but not ethnicity or immunosuppressive drugs at the time of vaccination. Patients with SSc were more likely to have asymptomatic COVID-19, but symptomatic patients reported more breathlessness. Hospitalization [SSc: 4 (14.8%), HCs: 37 (6.6%), non-SSc AIRDs: 32(15.8%)] and the need for oxygenation [SSc: 1 (25%); HC: 17 (45.9%); non-SSc AIRD: 13 (40.6%)] were similar between the groups. The incidence of BI in SSc was lower than that in HCs but comparable to that in non-SSc AIRDs. The severity of BI did not differ between the groups. Advancing age, but not ethnicity or immunosuppressive medication use, was associated with BIs.

Gender differences in patient experience in idiopathic inflammatory myopathies: Sub analysis from the COVAD dataset.

OBJECTIVES: We aimed to investigate gender-based differences in idiopathic inflammatory myopathies (IIMs), with a particular focus on patient-reported outcomes, utilizing data obtained through the international COVID-19 vaccination in autoimmune disease (COVAD) e-survey. METHODS: Patient-reported outcomes including fatigue, pain, and physical function were extracted from the COVAD database and compared between genders, adjusting for demographics and IIM subgroups by multivariable analysis. Inclusion body myositis (IBM) was analysed separately because of substantial differences in outcomes. RESULTS: 1197 complete responses from patients with IIMs as of 31 August 2021 were analysed. Seventy percent were women. Women were younger (58 [48-68] vs. 69 [58-75] years old, median [IQR], p < 0.001) and more likely to suffer from autoimmune multimorbidity, defined as three or more autoimmune diseases in an individual patient (11.4% vs. 2.8%, p < 0.001). In non-IBM IIMs, fatigue visual analogue scale scores were higher in women (5 [3-7] vs. 4 [2-6], median [IQR], p = 0.004), whereas no significant gender-based differences were noted in IBM. Multivariable analysis in non-IBM IIMs revealed women, residence in high-income countries, overlap myositis, and autoimmune multimorbidity were independently associated with increased fatigue. CONCLUSIONS: Women with IIMs suffer from autoimmune multimorbidity and experience increased fatigue compared to men.

Update on muscle imaging in myositis.

PURPOSE OF REVIEW: Imaging techniques such as MRI, ultrasound and PET/computed tomography (CT) have roles in the detection, diagnosis and management of myositis or idiopathic inflammatory myopathy (IIM). Imaging research has also provided valuable knowledge in the understanding of the pathology of IIM. This review explores the latest advancements of these imaging modalities in IIM. RECENT FINDINGS: Recent advancements in imaging of IIM have seen a shift away from manual and qualitative analysis of the images. Quantitative MRI provides more objective, and potentially more sensitive characterization of fat infiltration and inflammation in muscles. In addition to B-mode ultrasound changes, shearwave elastography offers a new dimension to investigating IIM. PET/CT has the added advantage of including IIM-associated findings such as malignancies. SUMMARY: It is evident that MRI, ultrasound and PET/CT have important roles in myositis. Continued technological advancement and a quest for more sophisticated applications help drive innovation; this has especially been so of machine learning/deep learning using artificial intelligence and the developing promise of texture analysis.

COVID-19 vaccine safety during pregnancy and breastfeeding in women with autoimmune diseases: results from the COVAD study.

OBJECTIVES: We investigated COVID-19 vaccine safety in pregnant and breastfeeding women with autoimmune diseases (AID) in the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. METHODS: Delayed-onset (>7 days) vaccine-related adverse events (AE), disease flares (DF), and AID-related treatment modifications were analyzed upon diagnosis of AID versus healthy controls (HC) and the pregnancy/breastfeeding status at the time of at least one dose of vaccine. RESULTS: Among the 9201 participants to the self-administered online survey, 6787 (73.8%) were women. Forty pregnant and 52 breastfeeding patients with AID were identified, of whom the majority had received at least one dose of COVID-19 vaccine (100% and 96.2%, respectively). AE were reported significantly more frequently in pregnant than in non-pregnant patients (overall AE 45% vs 26%, p= 0.01; minor AE 40% vs 25.9%, p= 0.03; major AE 17.5% vs 4.6%, p< 0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC with respect to AE. Post-vaccination DF were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18.3% of age- and disease-matched non-pregnant and non-breastfeeding patients (n = 262). All pregnant/breastfeeding patients who experienced a DF were managed with glucocorticoids; 28.6% and 20% of them required initiation or change in immunosuppressants, respectively. CONCLUSION: This study provides reassuring insights into the safety of COVID-19 vaccines administered to women with AID during the gestational and post-partum periods, helping overcome hesitant attitudes, as the benefits for the mother and the fetus by passive immunization appear to outweigh potential risks.

High fatigue scores in patients with idiopathic inflammatory myopathies: a multigroup comparative study from the COVAD e-survey.

Idiopathic inflammatory myopathies (IIMs) confer a significant risk of disability and poor quality of life, though fatigue, an important contributing factor, remains under-reported in these individuals. We aimed to compare and analyze differences in visual analog scale (VAS) scores (0-10 cm) for fatigue (VAS-F) in patients with IIMs, non-IIM systemic autoimmune diseases (SAIDs), and healthy controls (HCs). We performed a cross-sectional analysis of the data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) international patient self-reported e-survey. The COVAD survey was circulated from December 2020 to August 2021, and details including demographics, COVID-19 history, vaccination details, SAID details, global health, and functional status were collected from adult patients having received at least one COVID-19 vaccine dose. Fatigue experienced 1 week prior to survey completion was assessed using a single-item 10 cm VAS. Determinants of fatigue were analyzed in regression models. Six thousand nine hundred and eighty-eight respondents (mean age 43.8 years, 72% female; 55% White) were included in the analysis. The overall VAS-F score was 3 (IQR 1-6). Patients with IIMs had similar fatigue scores (5, IQR 3-7) to non-IIM SAIDs [5 (IQR 2-7)], but higher compared to HCs (2, IQR 1-5; P < 0.001), regardless of disease activity. In adjusted analysis, higher VAS-F scores were seen in females (reference female; coefficient -0.17; 95%CI -0.21 to -13; P < 0.001) and Caucasians (reference Caucasians; coefficient -0.22; 95%CI -0.30 to -0.14; P < 0.001 for Asians and coefficient -0.08; 95%CI -0.13 to 0.30; P = 0.003 for Hispanics) in our cohort. Our study found that patients with IIMs exhibit considerable fatigue, similar to other SAIDs and higher than healthy individuals. Women and Caucasians experience greater fatigue scores, allowing identification of stratified groups for optimized multidisciplinary care and improve outcomes such as quality of life.

Long-term safety of COVID vaccination in individuals with idiopathic inflammatory myopathies: results from the COVAD study.

Limited evidence on long-term COVID-19 vaccine safety in patients with idiopathic inflammatory myopathies (IIMs) continues to contribute to vaccine hesitancy. We studied delayed-onset vaccine adverse events (AEs) in patients with IIMs, other systemic autoimmune and inflammatory disorders (SAIDs), and healthy controls (HCs), using data from the second COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. A validated self-reporting e-survey was circulated by the COVAD study group (157 collaborators, 106 countries) from Feb-June 2022. We collected data on demographics, comorbidities, IIM/SAID details, COVID-19 history, and vaccination details. Delayed-onset (> 7 day) AEs were analyzed using regression models. A total of 15165 respondents undertook the survey, of whom 8759 responses from vaccinated individuals [median age 46 (35-58) years, 74.4% females, 45.4% Caucasians] were analyzed. Of these, 1390 (15.9%) had IIMs, 50.6% other SAIDs, and 33.5% HCs. Among IIMs, 16.3% and 10.2% patients reported minor and major AEs, respectively, and 0.72% (n = 10) required hospitalization. Notably patients with IIMs experienced fewer minor AEs than other SAIDs, though rashes were expectedly more than HCs [OR 4.0; 95% CI 2.2-7.0, p < 0.001]. IIM patients with active disease, overlap myositis, autoimmune comorbidities, and ChadOx1 nCOV-19 (Oxford/AstraZeneca) recipients reported AEs more often, while those with inclusion body myositis, and BNT162b2 (Pfizer) recipients reported fewer AEs. Vaccination is reassuringly safe in individuals with IIMs, with AEs, hospitalizations comparable to SAIDs, and largely limited to those with autoimmune multimorbidity and active disease. These observations may inform guidelines to identify high-risk patients warranting close monitoring in the post-vaccination period.

Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study.

Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group-robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)-at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

Systemic sclerosis and COVID-19 vaccine safety: short-term insights from the global COVID-19 vaccination in autoimmune disease (COVAD) survey.

The safety profile of COVID-19 vaccines is understudied in patients with systemic sclerosis (SSc). We compared short-term adverse events (AEs) 7 days following vaccination in patients with SSc vs other rheumatic (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). The COVID-19 Vaccination in autoimmune diseases (COVAD) self-reporting e-survey was circulated by a group of > 110 collaborators in 94 countries from March to December 2021. AEs were analyzed between different groups using regression models. Of 10,679 complete respondents [73.8% females, mean age 43 years, 53% Caucasians], 478 had SSc. 83% had completed two vaccine doses, Pfizer-BioNTech (BNT162b2) (51%) was the most common. Minor and major AEs were reported by 81.2% and 3.3% SSc patients, respectively, and did not differ significantly with disease activity or different vaccine types, though with minor symptom differences. Frequencies of AEs were not affected by background immunosuppression, though SSc patients receiving hydroxychloroquine experienced fatigue less commonly (OR 0.4; 95% CI 0.2-0.8). Frequency of AEs and hospitalisations were similar to other AIRDs, nrAIDs, and HC except a higher risk of chills (OR 1.3; 95% CI 1.0-1.7) and fatigue (OR 1.3; 95% CI 1.0-1.6) compared to other AIRDs. COVID-19 vaccines were largely safe and well tolerated in SSc patients in the short term. Background immunosuppression and disease activity did not influence the vaccination-related short-term AEs.