COVID-19 severity, breakthrough infections and vaccine safety in young individuals with autoimmune diseases: insights from the COVAD study.

Notwithstanding the wealth of literature on COVID-19, studies focusing on young adults with autoimmune diseases (AD) are lacking. To determine early (within 7 days) and late (after 7 days) anti-SARS-CoV-2 vaccine-related adverse events (AEs), post-vaccine disease flares, COVID-19 severity and breakthrough infections (B-INFs) in young people with rheumatic diseases (RMDs) and non-rheumatic autoimmune diseases (nr-ADs) compared to healthy controls (HC). Data were captured through the international COVID-19 vaccination in autoimmune diseases (COVAD) 1 and 2 questionnaires. Of 20,685 complete responses, we identified 6010 from patients aged 18-35 years (1692 RMD, 400 nrADs, 3918 HC) who received up to 4 vaccine doses. BNT162b2 was the most frequently administered vaccine and prior to vaccination, 7% of people with nrAD were taking immunosuppressants (IS) versus 80% in RMDs. Early mild AEs were more frequent in RMDs (93%) and nr-ADs (92%) compared to HC (85%). The frequency of late mild AEs was < 20% in all groups. Severe AEs were rare. SARS-CoV-2 infection rates were similar across all groups, however, RMD patients reported a single episode of infection more frequently than nrADs and HC, while nrADs reported multiple infections more frequently than RMD. Self-reported disease flares were reported by 10% or RMD and 7% of nrAD patients. Our study reinforces the safety of anti-SARS-CoV-2 vaccine also in young people with ADs, but it also highlights that among young individuals the number and clinical picture of SARS-CoV-2 infections is affected more by the type of AD rather than by coexisting IS therapy.

Characteristics of emerging new autoimmune diseases after COVID-19 vaccination: A sub-study by the COVAD group.

BACKGROUND: Despite the overall safety and efficacy of COVID-19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post-vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post-vaccination. METHODS: A cross-sectional study was conducted among participants with self-reported new-onset SAIDs using the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset-a validated, patient-reported e-survey-to analyze the long-term safety of COVID-19 vaccines. Baseline characteristics of patients with new-onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio. RESULTS: Of 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new-onset SAID post-vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new-onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9-9.7; p < .001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3-5.3; p = .004). New-onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1-1.7; p < .001), mental health disorders (OR = 1.6; 95% CI = 1.3-1.9; p < .001), and mixed race (OR = 2.2; 95% CI = 1.2-4.2; p = .010), where those aged >60 years (OR = 0.6; 95% CI = 0.4-0.8; p = .007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs. CONCLUSION: This study reports a low occurrence of new-onset SAIDs following COVID-19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre-existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID-19 vaccination in the general population. However, long-term studies are needed to understand the autoimmune phenomena arising post-vaccination.

Listening to patients, for the patients: The COVAD Study-Vision, organizational structure, and challenges.

BACKGROUND: The pandemic presented unique challenges for individuals with autoimmune and rheumatic diseases (AIRDs) due to their underlying condition, the effects of immunosuppressive treatments, and increased vaccine hesitancy. OBJECTIVES: The COVID-19 vaccination in autoimmune diseases (COVAD) study, a series of ongoing, patient self-reported surveys were conceived with the vision of being a unique tool to gather patient perspectives on AIRDs. It involved a multinational, multicenter collaborative effort amidst a global lockdown. METHODS: Leveraging social media as a research tool, COVAD collected data using validated patient-reported outcomes (PROs). The study, comprising a core team, steering committee, and global collaborators, facilitated data collection and analysis. A pilot-tested, validated survey, featuring questions regarding COVID-19 infection, vaccination and outcomes, patient demographics, and PROs was circulated to patients with AIRDs and healthy controls (HCs). DISCUSSION: We present the challenges encountered during this international collaborative project, including coordination, data management, funding constraints, language barriers, and authorship concerns, while highlighting the measures taken to address them. CONCLUSION: Collaborative virtual models offer a dynamic new frontier in medical research and are vital to studying rare diseases. The COVAD study demonstrates the potential of online platforms for conducting large-scale, patient-focused research and underscores the importance of integrating patient perspective into clinical care. Care of patients is our central motivation, and it is essential to recognize their voices as equal stakeholders and valued partners in the study of the conditions that affect them.

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.

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.

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.

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.

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.

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.

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.

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.

Delayed adverse events following COVID-19 vaccination in patients with systemic sclerosis and other autoimmune diseases: a substudy of the COVAD-2 cohort.

Data on short-term safety of COVID-19 vaccination in patients with systemic sclerosis (SSc) were explored previously in the first COVID-19 vaccination in autoimmune diseases (COVAD) survey conducted in 2021. However, delayed adverse events (ADEs) (occurring > 7 days post-vaccination) are poorly characterized in these patients with SSc. In this study, we analysed delayed COVID-19 vaccine-related ADEs among patients with SSc, other systemic autoimmune and inflammatory disorders (SAIDs) and healthy controls (HCs) using data from the second COVAD study conducted in 2022. The COVAD-2 study was a cross-sectional, patient self-reported global e-survey conducted from February to June 2022. Data on demographics, SSc/SAID disease characteristics, COVID-19 infection history, and vaccination details including delayed ADEs as defined by the Centre for Disease Control were captured and analysed. Among 17,612 respondents, 10,041 participants fully vaccinated against COVID-19 were included for analysis. Of these, 2.6% (n = 258) had SSc, 63.7% other SAIDs, and 33.7% were HCs. BNT162b2 Pfizer (69.4%) was the most administered vaccine, followed by MRNA-1273 Moderna (32.25%) and ChadOx1 nCOV-19 Oxford/AstraZeneca (12.4%) vaccines. Among patients with SSc, 18.9% reported minor, while 8.5% experienced major delayed ADEs, and 4.6% reported hospitalization. These frequencies were comparable to those of the ADEs reported by other patients with SAIDs and HCs. However, patients with SSc reported a higher frequency of difficulty in breathing than HCs [OR 2.3 (1.0-5.1), p = 0.042]. Patients with diffuse cutaneous SSc experienced minor ADEs [OR 2.1 (1.1-4.4), p = 0.036] and specifically fatigue more frequently [OR 3.9 (1.3-11.7), p = 0.015] than those with limited cutaneous SSc. Systemic sclerosis patients with concomitant myositis reported myalgia more frequently [OR 3.4 (1.1-10.7), p = 0.035], while those with thyroid disorders were more prone to report a higher frequency of joint pain [OR 5.5 (1.5-20.2), p = 0.009] and dizziness [OR 5.9 (1.3-27.6), p = 0.024] than patients with SSc alone. A diagnosis of SSc did not confer a higher risk of delayed post-COVID-19 vaccine-related ADEs overall compared with other SAIDs and HCs. However, the diffuse cutaneous phenotype and coexisting autoimmune conditions including myositis and thyroid disease may increase the risk of minor ADEs. These patients may benefit from pre-vaccination counselling, close monitoring, and early initiation of appropriate care in the post-COVID-19 vaccination period.

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.

Renal injury, biomarkers, and myositis, an understudied aspect of disease: prospective study in the MyoCite cohort.

Introduction: The mechanisms leading to chronic kidney disease (CKD) in patients with idiopathic inflammatory myopathies (IIMs) are poorly understood. We assessed the prevalence of subclinical renal injury in patients with IIMs, through elevation in biomarker levels of tubular injury and fibrosis (NGAL, KIM1, Activin A, CD163, and Cys-c), and assessed differences between subtypes of IIMs, and the effect of disease activity and duration. Materials and methods: Clinical data, core set measures, sera and urine were prospectively collected from all patients enrolled in the MyoCite cohort from 2017 to 2021. Twenty healthy subjects (HC) and 16 patients with acute kidney injury (AKI) were included as controls. Baseline and follow up data for IIMs were included. Enzyme-linked immunosorbent assay (ELISA) was used to measure urine NGAL (Human Lipocalin-2/NGAL Duoset ELISA, Cat no: DY1757), KIM1 (Human TIM-1/KIM 1/HAVCR Duoset ELISA, Cat.no: DY1750B), Activin A (Human Activin A Duoset ELISA, Cat no: DY338), CD163 (Human CD163 Duoset ELISA,Cat no: DY1607-05), and Cys-c (Human Cystatin C Duoset ELISA, Cat. no.: DY1196) levels, while eGFR (unit mL/min/1.73 m2) was calculated by the Cockcroft-Gault formula and CKD-EPI formula. Results: Analysis of 201 visits of 110 adult patients with IIMs indicated higher normalized biomarker levels compared to HCs, and comparable to patients with AKI, with the exception of NGAL, which was higher in the AKI group. Notably 72 (49%) patients with IIMs had eGFR<90; the levels of the 5 biomarkers were comparable between active and inactive IIMs, and different subtypes of IIMs. Similarly, a poor correlation between urine biomarker levels and core set measures of activity and damage was found. Changes in biomarker levels on follow-up did not correlate with eGFR changes. Discussion: This exploratory analysis of urinary biomarkers identified low eGFR and elevated biomarkers of CKD in nearly half of the patients with IIMs, comparable to patients with AKI and higher than HCs, indicative of potential renal damage in IIMs that may have a lead to complications in other systems.

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.