Biological and glucocorticoids treatment impair the medium-term immunogenicity to SARS-CoV-2 mRNA vaccines in autoimmune inflammatory rheumatic diseases.

BACKGROUND: This study aims to assess the sustained immunological response to the SARS-CoV-2 vaccine in patients with autoimmune inflammatory rheumatic diseases (AIRD) undergoing different treatment regimens. METHODS: We conducted a prospective observational study involving 157 AIRD patients without prior COVID-19 infection. Treatment regimens included non-treatment or glucocorticoid-only (not-treated/GCs), non-biological drugs, biological therapy, and JAK inhibitors. All participants completed the two-dose vaccine schedule, and 110 of them received an additional booster dose. Serum samples were collected approximately 3-6 months after the second and third vaccine doses to measure antibodies against the Spike protein (antiS-AB) and neutralizing antibodies (nAB) targeting six SARS-CoV-2 variants. RESULTS: Following the third dose, all patients exhibited a significant increase in antiS-AB (FC = 15, p < 0.0001). Patients under biological therapy had lower titres compared to the non-biological (66% decrease, p = 0.038) and the not-treated/GCs group (62% decrease, p = 0.0132), with the latter persisting after the booster dose (86% decrease, p = 0.0027). GC use was associated with lower antiS-AB levels in the biological group (87% decrease, p = 0.0124), although not statistically significant after confounders adjustment. nABs showed the highest positivity rates for the wild-type strain before (50%) and after the booster dose (93%), while the Omicron variant exhibited the lowest rates (11% and 55%, respectively). All variants demonstrated similar positivity patterns and good concordance with antiS-AB (AUCs from 0.896 to 0.997). CONCLUSIONS: The SARS-CoV-2 vaccine booster strategy effectively elicited a sustained antibody immune response in AIRD patients. However, patients under biological therapies exhibited a reduced response to the booster dose, particularly when combined with GCs.

Specific-cytokine associations with outcomes in knee osteoarthritis subgroups: breaking down disease heterogeneity with phenotyping.

BACKGROUND: Despite existing extensive literature, a comprehensive and clinically relevant classification system for osteoarthritis (OA) has yet to be established. In this study, we aimed to further characterize four knee OA (KOA) inflammatory phenotypes (KOIP) recently proposed by our group, by identifying the inflammatory factors associated with KOA severity and progression in a phenotype-specific manner. METHODS: We performed an analysis within each of the previously defined four KOIP groups, to assess the association between KOA severity and progression and a panel of 13 cytokines evaluated in the plasma and synovial fluid of our cohort's patients. The cohort included 168 symptomatic female KOA patients with persistent joint effusion. RESULTS: Overall, our analyses showed that associations with KOA outcomes were of higher magnitude within the KOIP groups than for the overall patient series (all p-values < 1.30e-16) and that several of the cytokines showed a KOIP-specific behaviour regarding their associations with KOA outcomes. CONCLUSION: Our study adds further evidence supporting KOA as a multifaceted syndrome composed of multiple phenotypes with differing pathophysiological pathways, providing an explanation for inconsistencies between previous studies focussed on the role of cytokines in OA and the lack of translational results to date. Our findings also highlight the potential clinical benefits of accurately phenotyping KOA patients, including improved patient stratification, tailored therapies, and the discovery of novel treatments.

Sex differential impact of comorbidities in spondyloarthritis: data from COMOSPA study.

OBJECTIVES: To describe and compare the prevalence of comorbidities in female and male patients with spondyloarthritis (SpA) and to assess whether comorbidities had a different impact on disease outcomes in male and female patients. METHODS: This is a post hoc analysis of the COMOrbidities in SPondyloArthritis study. Differences in comorbidities regarding sex were assessed using logistic regression models. Comorbidities were evaluated for their impact on disease outcomes (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index, European health-related quality of life questionnaire) with linear models, which included sex and comorbidity as explanatory variables and their interaction. Age and treatment with biological synthetic disease-modifying antirheumatic drugs were included as confounders. RESULTS: We included 3982 patients with SpA (65% male, mean age 43.6 years). Male and female patients with SpA exhibited similar comorbidity profiles, except for a low prevalence of fibromyalgia in males and a higher prevalence of certain cardiovascular risk factors in males (hypertension, dyslipidaemia, renal impairment and ischaemic heart disease). Comorbidities, especially fibromyalgia, correlated with higher disease activity, decreased physical function and reduced health-related quality of life in both sexes. Some comorbidities exhibited sex-specific associations with disease outcomes. Peptic ulcers and high waist circumference had a greater impact on disease activity in females (with a higher impact in BASDAI than in ASDAS). In contrast, osteoporosis had a more pronounced effect on physical function in male patients. CONCLUSIONS: Comorbidities exert distinct influences on disease activity, physical function and health-related quality of life in male and female patients with SpA. Understanding these sex-specific effects is crucial for improving SpA management, emphasising the importance of assessing disease activity using ASDAS when comorbidities are present to mitigate sex-related disparities in disease assessment.

Corrigendum: The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

[This corrects the article DOI: 10.3389/fimmu.2023.1191782.].

Implementation of the recommendations for the psychological management of patients with spondyloarthritis and inflammatory bowel disease.

OBJECTIVE: To assess and improve the level of implementation of the recommendations for the psychological management of patients with spondyloarthritis (SpA) and associated inflammatory bowel disease (IBD). METHODS: Qualitative study. We performed a narrative literature review to identify the recommendations for the psychological management of SpA and associated IBD and to explore their level of implementation. Based on the findings, we developed a national survey to assess: (1) current level of knowledge and implementation of the recommendations; (2) attitudes towards the recommendations; and (3) barriers and facilitators to their implementation. The results of the review and survey were discussed by a multidisciplinary group of 9 expert rheumatologists and gastroenterologists, who defined implementation strategies to increase the uptake of the recommendations. RESULTS: The review included 4 articles, 2 of them included direct recommendations on the identification and management of psychological problems in patients with SpA and IBD. None assessed the level of implementation of the recommendations in routine clinical practice. Our survey showed a great lack of awareness and implementation of the recommendations, even though psychological issues are very relevant for health professionals. Lack of time, resources, and knowledge are considered the main barriers to adherence to the recommendations. We propose several implementation strategies related to educational activities, clinical practice, and others to increase the uptake of reported recommendations. CONCLUSIONS: Further research and efforts are required to achieve behaviour changes in clinical practice to improve the identification and management of psychological problems and needs in patients with SpA and IBD.

Identification of the first signs or symptoms in different spondyloarthritis subtypes and their association with HLA-B27: data from REGISPONSER and RESPONDIA registries.

OBJECTIVE: To describe and analyse the initial symptoms attributable to patients with spondyloarthritis (SpA) and their association with HLA-B27 status. METHODS: This was an observational, cross-sectional and multicentre study with patients who fulfilled the European Spondyloarthropathy Study Group criteria for SpA from the Registry of Spondyloarthritis of Spanish Rheumatology (REGISPONSER) and Ibero-American Registry of Spondyloarthropathies (RESPONDIA) united registries. Differences in the first sign(s) or symptom(s) were compared across diagnoses and between HLA-B27 status. The diagnostic delay between patients who start the disease with musculoskeletal manifestations (MMs) and extra-MMs (EMMs) was compared. RESULTS: A total of 4067 patients were included (2208 from REGISPONSER and 1859 from RESPONDIA) (ankylosing spondylitis (AS): 68.3%, psoriatic arthritis (PsA): 19.9%, undifferentiated SpA: 11.8%). Overall, 3624 (89.1%) patients initiated the disease with MMs and 443 (10.9%) with EMMs. Low back pain (61.7%) and lower-limb arthritis (38.5%) were the most frequent initial symptoms. In AS patients, the absence of HLA-B27 seems to be related to an increase in the probability of starting the disease with cervical pain and peripheral manifestations. In PsA, the onset of arthritis and psoriasis was more prevalent in HLA-B27-negative patients, while initiation with axial manifestations was more predominant in HLA-B27-positive patients. The diagnostic delay was longer in patients with initial MMs than in those with EMMs (7.2 (34.8) vs 4.5 (7.6) years, respectively). CONCLUSION: In this SpA population, MMs were the most prevalent initial symptoms, with differences across diagnoses and depending on the presence of the HLA-B27 antigen.

The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4+ helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αß) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.

Validation of N Protein Antibodies to Diagnose Previous SARS-CoV-2 Infection in a Large Cohort of Healthcare Workers: Use of Roche Elecsys® Immunoassay in the S Protein Vaccination Era.

The aim of this study was to validate the detection of anti-nucleocapsid protein (N protein) antibodies for the diagnosis of SARS-CoV-2 infection in light of the fact that most COVID-19 vaccines use the spike (S) protein as the antigen. Here, 3550 healthcare workers (HCWs) were enrolled from May 2020 (when no S protein vaccines were available). We defined SARS-CoV-2 infection if HCWs were found to be positive by RT-PCR or found to be positive in at least two different serological immunoassays. Serum samples from Biobanc I3PT-CERCA were analyzed by Roche Elecsys® (N protein) and Vircell IgG (N and S proteins) immunoassays. Discordant samples were reanalyzed with other commercial immunoassays. Roche Elecsys® showed the positivity of 539 (15.2%) HCWs, 664 (18.7%) were found to be positive by Vircell IgG immunoassays, and 164 samples (4.6%) showed discrepant results. According to our SARS-CoV-2 infection criteria, 563 HCWs had SARS-CoV-2 infection. The Roche Elecsys® immunoassay has a sensitivity, specificity, accuracy, and concordance with the presence of infection of 94.7%, 99.8%, 99.3%, and 0.96, respectively. Similar results were observed in a validation cohort of vaccinated HCWs. We conclude that the Roche Elecsys® SARS-CoV-2 N protein immunoassay demonstrated good performance in diagnosing previous SARS-CoV-2 infection in a large cohort of HCWs.

Disease control in patients with psoriatic arthritis in real clinical practice in Spain: MiDAS study.

OBJECTIVE: MiDAS study assessed the percentage of psoriatic arthritis (PsA) patients treated in routine clinical practice who achieved control of disease activity according to Disease Activity in Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA). METHODS: Observational, non-interventional, cross-sectional, multicenter study conducted under conditions of routine clinical practice in 36 centers with outpatient rheumatology clinics in Spanish public hospitals. Patients included were adults (≥18 years) with ≥6 months PsA diagnosis according to classification for PsA (CASPAR) criteria and undergoing treatment ≥3 months. The main variable evaluated was the percentage of patients under remission and low disease activity, assessed through DAPSA and MDA. RESULTS: 313 patients with PsA were included: 54.3% male; with mean age of 54.1±12.2 years and mean disease duration of 10.5±9.0 years. Mean C-reactive protein (CRP) serum levels were 4.9±7.3mg/L. At the study visit, 58.5% of patients were in monotherapy (17.6% biological and 40.9% non-biological) and 41.2% were receiving biological and non-biological therapy. 59.4% of patients showed low disease activity (DAPSA≤14) and 19.8% were on remission (DAPSA≤4). Moreover, 51.4% of the patients reached an MDA status (≥5 MDA). CONCLUSIONS: Around 40% of PsA patients presented uncontrolled disease, highlighting the need to improve the management of these patients in clinical practice.

Patients with Axial Spondyloarthritis are Great Consumers of Healthcare Resources, Especially Young and Women: Results from the Spanish Atlas.

INTRODUCTION: This study aimed to assess high healthcare utilization over 1 year in patients with axial spondyloarthritis (axSpA) and factors associated with increased healthcare utilization. METHODS: A total of 530 unselected patients with axSpA from the Atlas of Axial Spondyloarthritis in Spain-who had used at least one healthcare resource-were included in the present study. Total health care utilization was obtained from the total number of healthcare visits, medical tests, hospital admissions and emergency visits, during the 12 months prior to the survey. Linear regression was used to analyse possible factors associated with higher healthcare utilization. RESULTS: A total of 530 patients with axSpA participated in this study: mean age was 45.3 years and 51.1% were female. In the previous 12 months, 77.9% (n = 530) used at least one healthcare resource, with the median healthcare utilization at 25. In the multiple linear regression, the only categorical factor associated with higher healthcare utilization was female gender (ß = 12.854), while the continuous factors associated with higher healthcare utilization were higher disease activity (ß = 3.378), longer diagnostic delay (ß = 0.959), younger age (ß = - 0.737) and greater functional limitation (ß = 0.576). CONCLUSION: Half of patients with axSpA used 25 or more healthcare resources during 1 year. Higher healthcare utilization was associated with younger age, female gender, greater disease activity, higher functional limitation and longer diagnostic delay. Optimal monitoring of patients with axSpA may help to reduce their healthcare utilization.

Metabolic and inflammatory profiles define phenotypes with clinical relevance in female knee osteoarthritis patients with joint effusion.

OBJECTIVES: Osteoarthritis has been the subject of abundant research in the last years with limited translation to the clinical practice, probably due to the disease's high heterogeneity. In this study, we aimed to identify different phenotypes in knee osteoarthritis (KOA) patients with joint effusion based on their metabolic and inflammatory profiles. METHODS: A non-supervised strategy based on statistical and machine learning methods was applied to 45 parameters measured on 168 female KOA patients with persistent joint effusion, consecutively recruited at our hospital after a monographic OA outpatient visit. Data comprised anthropometric and metabolic factors and a panel of systemic and local inflammatory markers. The resulting clusters were compared regarding their clinical, radiographic and ultrasound severity at baseline and their radiographic progression at two years. RESULTS: Our analyses identified four KOA inflammatory phenotypes (KOIP): a group characterized by metabolic syndrome, probably driven by body fat and obesity, and by high local and systemic inflammation (KOIP-1); a metabolically healthy phenotype with mild overall inflammation (KOIP-2); a non-metabolic phenotype with high inflammation levels (KOIP-3); and a metabolic phenotype with low inflammation and cardiovascular risk factors not associated with obesity (KOIP-4). Of interest, these groups exhibited differences regarding pain, functional disability and radiographic progression, pointing to a clinical relevance of the uncovered phenotypes. CONCLUSION: Our results support the existence of different KOA phenotypes with clinical relevance and differing pathways regarding their pathophysiology and disease evolution, which entails implications in patients' stratification, treatment tailoring and the search of novel and personalized therapies.

Disease control in patients with ankylosing spondylitis in real clinical practice in Spain: Results of the MIDAS study.

INTRODUCTION AND OBJECTIVES: Understanding the disease activity is fundamental to improve patient prognosis and patients' quality of life. MiDAS study described disease activity in ankylosing spondylitis (AS) Spanish patients and the proportion of them with controlled disease. METHODS: Observational, cross-sectional, multicenter study carried out under conditions of routine clinical practice. Adult (≥18 years) patients with ≥6 months since AS diagnosis treated ≥3 months prior to inclusion. The primary endpoint was the percentage of patients with low disease activity assessed through BASDAI (primary endpoint) and ASDAS-CRP (secondary endpoint). RESULTS: 313 AS patients included: 75.7% male; 78.5% HLA-B*27 positive; mean (SD) baseline age of 50.4 (12.0) years; mean (SD) disease duration of 15.5 (11.6) years; 73.5% were treated with biological disease-modifying antirheumatic drugs (DMARDs), 22.4% with non-biological DMARDs and 53.7% with non-steroidal anti-inflammatory drugs, alone or in combination. Monotherapy with biologics and non-biologics was used by 29.7% and 26.8% of patients, respectively. According to BASDAI, 38.0% were in remission (BASDAI≤2) and 64.5% showed adequate disease control (BASDAI<4). According to ASDAS-CRP, 29.4% achieved remission (ASDAS-CRP<1.3) and 28.1% low disease activity (1.3≤ASDAS-CRP<2.1). CONCLUSIONS: Almost two thirds of the AS patients recruited had low disease activity, with about one third of them being in remission (BASDAI≤2, ASDAS-CRP<1.3). These results highlight the existing room for improvement in treating AS patients in clinical practice.

Expert recommendations for the use of apremilast in psoriatic arthritis.

INTRODUCTION AND OBJECTIVES: Despite the evidence, there are doubts about the positioning of apremilast in the psoriatic arthritis (PsA) treatment algorithm. The objective of this project was to collect the scientific evidence and the experience of a group of rheumatologists who are experts in the management of PsA with apremilast in clinical practice in Spain. MATERIAL AND METHODS: A scientific committee made up of 6 experts proposed 5 clinical scenarios where the evidence on the use of apremilast in PsA was controversial: (i) Efficacy in peripheral PsA; (ii) Efficacy in enthesitis and dactylitis; (iii) Efficacy in PsA with skin involvement; (iv) Comorbidities; and (v) Apremilast safety. After this, a panel of 17 rheumatologists with expertise in PsA management discussed these scenarios and generated a questionnaire with 50 questions and 156 items following the Delphi methodology. This questionnaire was anonymously answered by the panel. RESULTS: After 2 voting rounds, the panel of experts reached consensus in 93 of the 156 items raised (59.6%) (67 in agreement and 26 in disagreement). The degree of consensus was 53.3% in the area of "Efficacy in peripheral PsA"; 60.0% in "Efficacy in enthesitis and dactylitis"; 50.0% in "Efficacy in PsA with skin involvement"; 57.1% in "Management of comorbidities in patients with PsA"; and 67.3% in "Implications of safety in the use of apremilast". CONCLUSIONS: The structured opinion of the experts complements the available evidence and contributes to the establishment of consensual guidelines for the use of apremilast in PsA.

Resources and strategies for the optimal care of patients with axial spondyloarthritis: The CREA project.

BACKGROUND AND OBJECTIVE: Axial spondyloarthritis (axSpA) are musculoskeletal diseases with different manifestations. In clinical practice, variability, and limitations in the collection of the outcomes required for follow-up have been observed. The objective of the CREA project was to agree on improvement strategies for the initial assessment and follow-up of patients with axSpA in Spain. MATERIALS AND METHODS: A survey with 33 questions was conducted by a representative sample of rheumatologists on clinical practice, resources, and present limitations in the follow-up of patients with axSpA. The results of the survey were discussed in 10 regional meetings, and 105 strategies were proposed and evaluated through a Delphi consensus in which 85 experts participated. RESULTS: The lack of time for clinical visits, the lack of nurses and/or support staff and the delay in performing the imaging tests were the most prominent limitations in the follow-up of patients with axSpA. One hundred and five strategies were proposed related to the evaluation of disease activity, physical function, quality of life and disease impact, to the evaluation of comorbidities and extra-articular manifestations, laboratory tests; imaging tests, physical examination and metrology. Of the total, 85 were considered highly advisable. No regional differences were found. CONCLUSIONS: The proposals agreed upon as highly advisable in the present study are applicable to the entire national territory, allow tighter and more homogeneous monitoring of the patients with axSpA, facilitate more comprehensive management of the disease, and respond to the unmet needs detected in the initial survey.

Strategies and resources to optimise the management of Psoriatic Arthritis patients: The CREA Project.

BACKGROUND AND AIM: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease that affects the musculoskeletal system and skin, and manifests heterogeneously, with a variable course. In current clinical practice, variability and limitations in its follow-up have been observed. The aim of the CREA project was to agree on strategies to improve the initial assessment and follow-up of patients with PsA in Spain. MATERIALS AND METHODS: A survey was conducted among a representative sample of expert rheumatologists in Spain, containing 33 questions on current clinical practice, available resources, and current limitations in the follow-up of patients with PsA. The results were discussed in regional meetings and 105 strategies were proposed and finally evaluated by 85 experts in a Delphi consensus. RESULTS: The most important limitations in the follow-up of PsA were lack of consultation time, lack of nursing staff, and delays in performing imaging tests. A total of 108 strategies were proposed related to the assessment of quality of life and disease-impact indices; comorbidities and extra-articular manifestations; laboratory tests; imaging tests; physical examination and metrology; and activity and function indices. Of the total, 53 were considered highly advisable, with no regional differences in consensus values. DISCUSSION AND CONCLUSIONS: The proposals offered in the current study are applicable to the entire country, respond to the unmet needs detected in the initial survey, form a minimum action framework, and ensure optimal follow-up of patients with PsA.

Uveitis in peripheral spondyloarthritis patients: an ancillary analysis of the ASAS-PerSpA study.

Background: Acute anterior uveitis (AAU) is the most frequent extra-musculoskeletal manifestation in spondyloarhtritis (SpA). Previous data on AAU focused on axial disease; therefore, it is not well known whether the clinical characteristics of patients with AAU and recurrent AAU differ between patients with axial and peripheral SpA. Objective: Primary objective was to compare the clinical characteristics of patients with AAU from patients without AAU in axial and peripheral spondyloarthritis (SpA) patients. Secondary objectives were to describe the clinical features of patients with AAU in the subset of patients with peripheral SpA (pSpA) and the clinical characteristics of patients with recurrent AAU in SpA patients. Design: This is an ancillary analysis of the ASAS-PerSpA study which included 3152 patients, 2719 patients with axSpA and 433 with pSpA according to rheumatologist judgement. Methods: Recurrent AAU was defined as the presence of two or more episodes of AAU ever. Univariable and multivariable binary logistic regression analyses were conducted to identify factors associated with the presence of AAU ever and the presence of recurrent AAU. Results: Overall, 663 patients (21%) presented AAU. Of them, 444 (66.9%) presented recurrent episodes. In patients with SpA, HLA-B27 positivity is the most important factor linked to the presence of AAU, odds ratio (OR) = 2.70 (95% CI = 2.04-3.6). In patients with pSpA, HLA-B27 positivity was also the most relevant factor linked to the presence of AAU, OR = 6.08 (95% CI = 2.72-15.68). Moreover, disease duration, younger age and higher body mass index (BMI) were the only factors slightly linked to the presence of recurrent episodes, OR = 1.03 (95% CI = 1.01-1.04), OR = 1.01 (95% CI = 1.00-1.03) and OR = 1.04 (95% CI = 1.01-1.08), respectively. Conclusion: HLA-B27 positivity is the most relevant factor linked to AAU risk in SpA patients, and this association is even stronger in those patients with pSpA. Moreover, our study did not find an association between HLA-B27 positivity and recurrent AAU in SpA patients.

SARS-CoV-2 Spike Protein Vaccine-Induced Immune Imprinting Reduces Nucleocapsid Protein Antibody Response in SARS-CoV-2 Infection.

Immune imprinting or original antigenic sin (OAS) is the process by which the humoral memory response to an antigen can inhibit the response to new epitopes of that antigen originating from a second encounter with the pathogen. Given the situation of the COVID-19 pandemic, multiple vaccines have been developed against SARS-CoV-2 infection. These vaccines are directed to the spike protein (S protein) of the original variant of Wuhan D614G. Vaccine memory immune response against S protein in noninfected subjects could inhibit, through the OAS mechanism, the response to new epitopes of SARS-CoV-2 after infection. The present study analyzes whether the memory antibody B cell response generated by mRNA vaccines against S protein can inhibit the primary antibody immune response to other SARS-CoV-2 antigens, such as nucleocapsid protein (N protein). SARS-CoV-2 primary infection in vaccinated healthcare workers (HCWs) produced significantly lower titers of anti-N antibodies than that in nonvaccinated HCWs: 5.7 (IQR 2.3-15.2) versus 12.2 (IQR 4.2-32.0), respectively (p = 0.005). Therefore, spike protein vaccine-induced immune imprinting (original antigenic sin) reduces N protein antibody response.

Glucocorticoids' treatment impairs the medium-term immunogenic response to SARS-CoV-2 mRNA vaccines in Systemic Lupus Erythematosus patients.

Limited data exists on SARS-CoV-2 sustained-response to vaccine in patients with rheumatic diseases. This study aims to evaluate neutralizing antibodies (nAB) induced by SARS-CoV-2 vaccine after 3 to 6 months from administration in Systemic Lupus Erythematosus (SLE) patients, as a surrogate of sustained-immunological response. This cross-sectional study compared nAB titre of 39 SLE patients and 37 Healthy individuals with no previous SARS-CoV-2 infection, who had all received a complete regimen of a mRNA SARS-CoV-2 vaccine within the last 3 to 6 months. We included four lines of SLE treatment including Not-treated, Hydroxychloroquine, immunosuppressive drugs and biological therapy. Glucocorticoids were allowed in all groups. Healthy and Not-treated individuals showed the highest levels of nAB. Treated patients presented lower nAB titres compared to Healthy: a 73% decrease for First-Line patients, 56% for Second-Line treatment and 72% for Third-Line. A multivariate analysis pointed to Glucocorticoids as the most associated factor with declining nAB levels (75% decrease) in treated SLE. Furthermore, a significant reduction in nAB titres was observed for Rituximab-users compared to Healthy subjects (89% decrease). Medium-term response of SLE patients to SARS-CoV-2 mRNA vaccines is negatively impacted in Glucocorticoids and Rituximab users. These findings might help to inform recommendations in vaccination protocols for SLE patients.

Antibody Response Induced by BNT162b2 and mRNA-1273 Vaccines against the SARS-CoV-2 in a Cohort of Healthcare Workers.

The aim of this study was to characterize the antibody response induced by SARS-CoV-2 mRNA vaccines in a cohort of healthcare workers. A total of 2247 serum samples were analyzed using the Elecsys® Anti-SARS-CoV-2 S-test (Roche Diagnostics International Ltd., Rotkreuz, Switzerland). Sex, age, body mass index (BMI), arterial hypertension, smoking and time between infection and/or vaccination and serology were considered the confounding factors. Regarding the medians, subjects previously infected with SARS-CoV-2 who preserved their response to the nucleocapsid (N) protein showed higher humoral immunogenicity (BNT162b2: 6456.0 U/mL median; mRNA-1273: 2505.0 U/mL) compared with non-infected (BNT162b2: 867.0 U/mL; mRNA-1273: 2300.5 U/mL) and infected subjects with a lost response to N protein (BNT162b2: 2992.0 U/mL). After controlling for the confounders, a higher response was still observed for mRNA-1273 compared with BNT162b2 in uninfected individuals (FC = 2.35, p < 0.0001) but not in previously infected subjects (1.11 FC, p = 0.1862). The lowest levels of antibodies were detected in previously infected non-vaccinated individuals (39.4 U/mL). Clinical variables previously linked to poor prognoses regarding SARS-CoV-2 infection, such as age, BMI and arterial hypertension, were positively associated with increasing levels of anti-S protein antibody exclusively in infected subjects. The mRNA-1273 vaccine generated a higher antibody response to the S protein than BNT162b2 in non-infected subjects only.

Similarities and differences between non-radiographic and radiographic axial spondyloarthritis: The patient perspective from the Spanish atlas.

AIM: Although non-radiographic axial spondyloarthritis (EspAax-nr) is well understood within health institutions, being considered along with radiographic EspAax (EspAax-r) as part of the same disease spectrum, patient understanding is unknown. The aim is to describe the patient's knowledge of the EspAax-nr entity. METHODS: Atlas 2017, promoted by the Spanish Federation of Spondylarthritis Associations (CEADE), aims to comprehensively understand the reality of EspAax patients from a holistic approach. A cross-sectional on-line survey of unselected patients with self-reported EspAax diagnosis from Spain was conducted. Participants were asked to report their diagnosis. Socio-demographic, disease characteristics and patient-reported outcomes (PROs) were compared between those patients self-reporting as EspAax-nr and EspAax-r. RESULTS: 634 EspAax patients participated. Mean age 45.7±10.9 years, 50.9% female and 36.1% university-educated. 35 (5.2%) self-reported as EspAax-nr. Compared to EspAax-r patients, those with EspAax-nr were more frequently women (48.6% vs 91.4%, p<0.001), had longer diagnostic delay (10.1±8.9 vs 8.5±7.6 years), higher psychological distress (GHQ-12: 7.5±4.9 vs 5.6±4.4) and similar degree of disease activity (BASDAI: 5.7±2.1 vs 5.7±2.0), and unemployment rates (20.0% vs 21.6%). 20.0% of EspAax-nr received biologics vs 36.9% of EspAax-r, p=0.043. Visits to the rheumatologist in the past year were similar in both groups (3.8±4.5 vs 3.2±3.8), while GP visits were much higher within EspAax-nr (8.0±10.7 vs 4.9±13.3 p=0.003). CONCLUSION: For the first time, EspAax-nr characteristics and PROs have been analyzed from the patient's perspective. Both groups reported similar trends with the exception of EspAax-nr being more frequently women, younger, having longer diagnostic delay and lower use of biologic therapy.