Background Quality of care is receiving increased attention in systemic lupus erythematosus (SLE). We developed quality indicators (QIs) for SLE based on the 2019 update of European League Against Rheumatism recommendations. Methods A total of 44 candidate QIs corresponding to diagnosis, monitoring and treatment, were independently rated for validity and feasibility by 12 experts and analysed by a modified Research and Development Corporation/University of California Los Angeles model. Adherence to the final set of QIs and correlation with disease outcomes (flares, hospitalisations and organ damage) was tested in a cohort of 220 SLE patients with a median monitoring of 2 years (IQR 2–4). Results The panel selected a total of 18 QIs as valid and feasible. On average, SLE patients received 54% (95% CI 52.3% to 56.2%) of recommended care, with adherence ranging from 44.7% (95% CI 40.8% to 48.6%) for diagnosis-related QIs to 84.3% (95% CI 80.6% to 87.5%) for treatment-related QIs. Sustained remission or low disease activity were achieved in 26.8% (95% CI 21.1% to 33.2%). Tapering of prednisone dose to less than 7.5 mg/day was achieved in 93.6% (95% CI 88.2% to 97.0%) while 73.5% (95% CI 66.6% to 79.6%) received the recommended hydroxychloroquine dose. Higher adherence to monitoring-related QIs was associated with reduced risk for a composite adverse outcome (flare, hospitalisation or damage accrual) during the last year of observation (OR 0.97 per 1% adherence rate, 95% CI 0.96 to 0.99). Conclusion We developed QIs for assessing and improving the care of SLE patients. Initial real-life data suggest face validity, but a variable degree of adherence and a need for further improvement.

There are limited real-life data regarding the efficacy and safety of rituximab (RTX) as a remission-maintenance agent in microscopic-polyangiitis (ΜPA) and granulomatosis-with-polyangiitis (GPA). We aimed to estimate the incidence and risk factors for relapses, as well serious-adverse-events (SAEs) in MPA/GPA patients during RTX-maintenance. Retrospective cohort of newly-diagnosed/relapsing GPA/MPA patients who received RTX-maintenance (≥1 RTX-cycle, ≥6 months follow-up) following complete-remission (Birmingham-Vasculitis-Activity-Score-version-3 = 0 plus prednisolone ≤7.5 mg/day) with induction regimens. SAEs included serious-infections, COVID-19-associated hospitalizations, deaths, cardiovascular-events, malignancies and hypogammaglobulinemia. Incidence-rates (IR) and relapse-free survival through Kaplan-Meier plots were estimated. Cox-regression was conducted to investigate factors associated with the time-to-relapse. 101 patients were included; 48% females, 69% GPA, 53% newly diagnosed, median age: 63 years. During follow-up (294.5 patient-years, median: 3 RTX-cycles), 30 relapses (57% major) occurred among 24 patients (24%, IR 10.2/100 patient-years). Kidney involvement (adjusted-Hazard-Ratio/aHR: 0.20; 95% CI: 0.06–0.74, p= 0.016), prior induction with RTX plus cyclophosphamide (vs RTX monotherapy: aHR = 0.02; 95% CI: 0.001–0.43, p= 0.012) and shorter time-interval until complete-remission (aHR = 1.07; 95% CI: 1.01–1.14, p= 0.023) were associated with decreased relapse-risk. We recorded 17 serious-infections (IR 5.8/100 patient-years), 11 COVID-19-associated hospitalizations (IR 3.7/100 patient-years), 4 malignancies (IR 1.4/100 patient-years), 6 cardiovascular-events (IR 2/100 patient-years) and 10 deaths (IR 3.4/100 patient-years). In this real-world study, relapses during RTX-maintenance occurred in approximately in 1 out of 4 patients. Kidney involvement, induction with RTX plus cyclophosphamide and earlier achievement of complete-remission were associated with lower relapse-risk. Serious-infections rate was consistent with previous reports, whereas an increased rate of COVID19-associated hospitalizations was observed.

To discern predictive factors for incident kidney involvement in patients with SLE. Patients with SLE from the ‘Attikon’ Lupus cohort were monitored for LN, defined by kidney histology and/or classification criteria. Demographic and clinical characteristics at baseline were compared against patients who did not develop LN. LN-free Kaplan–Meier survival curves were generated. A multivariate Cox proportional hazards model was used to identify independent predictors of LN. Independent validation was performed in the University of Crete Lupus registry. Among the 570 patients in the derivation cohort, 59 exhibited LN as their initial presentation, while an additional 66 developed LN during the follow-up period (collectively, 21.9% incidence). In the latter group, baseline factors predictive of subsequent kidney involvement were male sex [multivariable-adjusted hazard ratio (aHR) 4.31; 95% CI: 1.82, 10.2], age of SLE diagnosis below 26 years (aHR 3.71; 95% CI: 1.84, 7.48), high anti-dsDNA titre (aHR 2.48; 95% CI: 1.03, 5.97) and low C3 and/or C4 (although not statistically significant, aHR 2.24; 95% CI: 0.83, 6.05; P = 0.11). A combination of these factors at time of diagnosis conferred an almost 90-fold risk compared with serologically inactive, older, female patients (aHR 88.77; 95% CI: 18.75, 420.41), signifying a very high-risk group. Independent validation in the Crete Lupus registry showed concordant results with the original cohort. Male sex, younger age and serological activity at SLE diagnosis are strongly associated with subsequent kidney involvement. Vigilant surveillance and consideration of early use of disease-modifying drugs is warranted in these subsets of patients.

The management of neuropsychiatric systemic lupus erythematosus (NPSLE) remains challenging because of clinical heterogeneity and the complexity of pathophysiologic mechanisms involved. We sought to determine the molecular signature of NPSLE and its endotypes towards novel biomarkers and targeted therapies. Whole-blood RNA sequencing from 308 patients with systemic lupus erythematosus (119 with NPSLE, 189 non-NPSLE) and 72-matched healthy controls (HCs) were performed. Supervised pathway enrichment analysis and unsupervised weighted gene coexpression network analysis were applied to distinguish clinically and molecularly defined NPSLE endotypes. Compared with HCs, patients with NPSLE demonstrated dysregulation of adaptive immune responses along with upregulation of interleukin (IL)-1, IL-6, IL-17, and IL-12/IL-23 signalling pathways. The comparison between NPSLE and non-NPSLE groups revealed a robust upregulation of complement cascade, DNA damage response, adaptive immunity, and IL-1 and IL-6 signalling. Furthermore, active NPSLE exhibited a strong autophagy signature. The B cell and complement cascade signatures exhibited a gradual upregulation across the non-NPSLE, inactive NPSLE, and active NPSLE subgroups. Within NPSLE, diffuse syndromes correlated positively with the oxidative phosphorylation module, while antiphospholipid antibody-positive NPSLE was not associated with specific signatures by unsupervised analysis. NPSLE endotypes such as cognitive dysfunction, seizures, psychosis, and optic neuritis were associated with distinct transcriptomic signatures namely IL-6 signalling and leukocyte migration, DNA damage response, inflammation, and type-I interferon, respectively. The clinical heterogeneity of NPSLE appears to be associated with molecular diversity, with certain endotypes or syndromes exhibiting distinct gene signatures. Upregulation of adaptive immune response and complement cascade suggests that complement inhibitors and B cell-targeted therapies could be further explored in NPSLE.

Background: COVID-19 may persist or relapse in patients on B-cell depleting biologic therapies. Objective: To examine the rate and outcome of persistent-relapsing COVID-19 (prCOVID-19) in patients with autoimmune rheumatic diseases (AIRD) treated with rituximab (RTX). Methods: Single-centre, retrospective cohort study of patients diagnosed with prCOVID-19 (June 2021 to January 2025). prCOVID-19 was defined as persistence of symptoms and lung imaging findings for >30 days, along with persistently positive or PCR-based conversion in upper or lower respiratory tract samples. Results: 26 out of 225 (11.6%) AIRD patients, previously diagnosed with COVID-19 during RTX treatment period, developed 27 prCOVID-19 events (females: 20 (76.9%), median age: 61 years, median disease duration: 5.5 years, ≥3 COVID-19 vaccine doses: 20 (76.9%)). No prCOVID-19 infection in a control sample of 661 patients treated with other biologic/targeted synthetic/conventional synthetic disease-modifying antirheumatic drugs was documented. Median cumulative RTX dose was 12 g, while in 17 (68%) prCOVID-19 events, IgG levels were below 700 mg/L. Median duration of prCOVID-19 infection was 65 (IQR 74) days and median duration of hospitalisation 10.5 (IQR 14) days. 11 patients (42.3%) had ≥2 hospitalisations, 3 patients needed mechanical ventilation and 4 deaths were recorded. 59 of 113 (52.2%) nasopharyngeal PCR samples (NPS) and 12/17 (70.6%) bronchoalveolar lavage (BAL) PCR samples were positive during prCOVID-19. Bronchoscopy established the diagnosis of prCOVID-19 in 33% of events. Conclusion: AIRD patients treated with RTX are at risk for prCOVID-19. In such patients, the diagnostic accuracy of NPS PCR is suboptimal, necessitating PCR testing in BAL when prCOVID-19 is highly suspected.

Introduction: Currently approved SARS-CoV-2 vaccines have been proven effective in protecting against severe COVID-19; however, they show variable efficacy against symptomatic infection and disease transmission. We studied the breakthrough COVID-19 infection (BTI) after booster vaccination against SARS-CoV-2 in people living with HIV (PWH). Methods: This was a retrospective, single-center, descriptive cohort study involving PWH, who were followed in the HIV Clinic of “Attikon” University Hospital in Athens, Greece. A BTI was defined as a case of laboratory-confirmed COVID-19 occurring at least 14 days after the third (booster) vaccine dose. Results: We studied 733 PWH [males: 89%, mean age: 45.2 ± 11.3 years, mean BMI: 26.1 ± 4.1, HIV stage at diagnosis (CDC classification): A/B/C = 80/9/11%, MSM: 72.6%] with well-controlled HIV infection. At least one comorbidity was recorded in 54% of cases. A history of ≥1 vaccination was reported by 90%, with 75% having been vaccinated with ≥3 vaccines. Four hundred and two (55%) PWH had a history of COVID-19 and 302 (41.2%) had a BTI, with only 15 (3.7%) needing hospitalization. Only one patient was admitted to the ICU, and no death was reported. Regarding BTI after booster dose, increased age (OR = 0.97, 95% CI: 0.96–0.99, per 1-year increase), and COVID-19 infection prior to booster dose (OR = 0.38, 95% CI: 0.21–0.68) were associated with a lower likelihood for BTI, whereas higher BMI (OR = 1.04, 95% CI: 1.01–1.08) and MSM as a mode of HIV transmission were associated with increased risk (OR = 2.59, 95% CI: 1.47–4.56). The incidence rate of total COVID-19 and BTI followed the epidemic curve of the general population, with the highest incidence recorded in June 2022. Conclusions: A significant proportion of PWH with well-controlled HIV infection experienced a BTI, with the majority of them having mild infection. These data, which include the period of Omicron variant predominance, confirm the importance of vaccination in the protection against severe COVID-19.