Characteristics of long COVID in patients with autoimmune rheumatic diseases: a systematic review and meta-analysis.

Objectives: Numerous cases of long coronavirus disease (long COVID) have been reported in patients with autoimmune rheumatic diseases (ARDs). Despite the reviews on clinical manifestations of long COVID in the general population, systematic reviews on ARD patients are scarce. Herein, we conducted a systematic review and meta-analysis on the prevalence and characteristics of long COVID in ARD patients. Methods: We searched the literature in PubMed and Embase as of 27 December 2022. Cohort, cross-sectional and case-control studies relevant to long COVID in ARD patients were collected. Stratification based on the severity of COVID infection and subtypes of rheumatic diseases [systemic autoimmune rheumatic disease (SARD) vs non-autoimmune rheumatic disease (NARD)] was also undertaken. A random-effects model was used in the meta-analysis. Results: A total of 15 relevant studies were identified from the literature. The prevalence of long COVID was 56% (95% CI 34, 76) in 2995 patients. Hospitalized COVID patients had a higher proportion of long COVID than non-hospitalized patients. The prevalence of long COVID was similar between SARD and NARD patients. In terms of symptoms, fatigue, arthralgia and pain were commonly reported in long COVID patients with ARDs. Conclusion: The characteristics of long COVID in ARD patients are generally similar to those in the general population despite a higher prevalence and a higher proportion of arthralgia and pain.

Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C.

Notwithstanding recent advances in direct antiviral specialists (DAAs) for hepatitis C infection (HCV), it is yet a pervasive overall issue in patients with rheumatoid arthritis (RA). Exosomal microRNAs (miRNAs) is associated with HCV infection. However, it remains unknown how miRNAs respond following biologic disease-modifying antirheumatic drug (bDMARD) and targeted synthetic DMARD (tsDMARD) treatment in HCV patients with RA. We prospectively recruited RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors rituximab (RTX) and tofacitinib. The serum hepatitis C viral load was measured using real-time quantitative reverse transcriptase PCR before and 6 months after bDMARD and tsDMARD therapy. HCV RNA replication activity was measured using an HCV-tricistronic replicon reporter system, and quantitative analysis of hsa-mir-122-5p and hsa-mir-155-5p in patients was performed using quantitative PCR. HCV RNA replication in hepatocytes was not affected by tofacitinib or TNF-α inhibitor treatment. Hsa-mir-155-5p and hsa-mir-122-5p were significantly expanded in RA patients with HCV as compared with those without HCV. We observed a dramatic increase in hsa-mir-122-5p and a decrease in hsa-mir-155-5p expression levels in patients taking RTX in comparison with other treatments. Finally, a reduction in hsa-mir-122-5p and an increase in hsa-mir-155-5p were observed in a time-dependent manner after tofacitinib and DAA therapy in RA-HCV patients. These results showed that hsa-mir-155-5p and hsa-mir-122-5p were significantly increased in RA-HCV patients as compared with those without HCV after taking tofacitinib. Hsa-mir-155-5p and hsa-mir-122-5p may be potential biomarkers for treatment efficacy in RA patients with HCV.

The NLRP3 Inflammasome as a Pathogenic Player Showing Therapeutic Potential in Rheumatoid Arthritis and Its Comorbidities: A Narrative Review.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by chronic synovitis and the progressive destruction of cartilage and bone. RA is commonly accompanied by extra-articular comorbidities. The pathogenesis of RA and its comorbidities is complex and not completely elucidated. The assembly of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activates caspase-1, which induces the maturation of interleukin (IL)-1ß and IL-18 and leads to the cleavage of gasdermin D with promoting pyroptosis. Accumulative evidence indicates the pathogenic role of NLRP3 inflammasome signaling in RA and its comorbidities, including atherosclerotic cardiovascular disease, osteoporosis, and interstitial lung diseases. Although the available therapeutic agents are effective for RA treatment, their high cost and increased infection rate are causes for concern. Recent evidence revealed the components of the NLRP3 inflammasome as potential therapeutic targets in RA and its comorbidities. In this review, we searched the MEDLINE database using the PubMed interface and reviewed English-language literature on the NLRP3 inflammasome in RA and its comorbidities from 2000 to 2023. The current evidence reveals that the NLRP3 inflammasome contributes to the pathogenesis of RA and its comorbidities. Consequently, the components of the NLRP3 inflammasome signaling pathway represent promising therapeutic targets, and ongoing research might lead to the development of new, effective treatments for RA and its comorbidities.

The Fracture Risk of Elderly Patients With Atopic Dermatitis.

Background: A higher fracture risk has been reported previously in patients with atopic dermatitis (AD). The bone mineral density (BMD) was not accounted for in these studies. Objective: To investigate the fracture risk in AD patients after adjustment for factors including BMD. Methods: We retrospectively analyzed AD patients (≥45 years) who underwent BMD examination at our hospital from July 2010 to February 2023. Individuals who received BMD examinations during a health checkup were identified as the controls. We documented their clinical characteristics, BMD, 10-year risk for a major fracture based on FRAX (Fracture Risk Assessment Tool), and development of osteoporotic fractures. Patients were followed until development of new onset fracture or the end of the study period. A cross-sectional comparison of BMD between AD patients and controls at baseline was performed using the Mann-Whitney U test after propensity score matching (PSM). Their fracture risks were compared using the multivariate Cox regression model. BMD and fracture risk were also compared between AD patients who received systemic therapy and those who did not. Results: A total of 50 AD patients and 386 controls were enrolled. The median age was older in AD patients when compared with controls (70 years vs 60 years). Their BMD at all sites was similar after PSM. After a median follow-up of 1.7-2.0 years, 13 osteoporotic fractures were identified. In the multivariate Cox regression analysis, AD was not associated with new onset fractures of all sites (adjusted hazard ratio [aHR] 2.55, 95% confidence interval [CI] 0.72-9.01) but was significantly associated with new onset vertebral fractures (aHR 6.80, 95% CI 1.77-26.17). The BMD and incidence of fractures were similar between AD who received systemic therapy and those who did not. Conclusions: Elderly AD patients had similar BMD but a higher short-term risk for vertebral fractures when compared with the controls.

Increased NAFLD risk in newly diagnosed patients with RA during the first 4 years of follow-up: a nationwide, population-based cohort study.

BACKGROUND: Although the non-alcoholic fatty liver disease (NAFLD) is prevalent in the general population, NAFLD risk in newly diagnosed rheumatoid arthritis (RA) has rarely been explored. In this population-based cohort, we examined NAFLD risk in patients with RA and identified the potential risk factors. DESIGN: Retrospective study. SETTING: Taiwan. PARTICIPANTS: 2281 newly diagnosed patients with RA and selected 91 240 individuals without RA to match with patients with RA (1:40) by age, gender, income status and urbanisation level of the residence. OUTCOMES: In this retrospective study using the 2000-2018 claim data from two-million representative Taiwanese population, we identified and compared the incidence rates (IRs) of NAFLD and alcoholic fatty liver disease (AFLD) between RA and non-RA groups. Using multivariable regression analyses, we estimated adjusted HR (aHR) of NAFLD development in patients with RA compared with individuals without RA, with 95% CIs. RESULTS: The incidences of NALFD and AFLD were not significantly different between individuals with RA and without RA during the 17-year follow-up period. However, patients with RA had significantly increased NAFLD risk during the first 4 years after RA diagnosis, with IR ratio of 1.66 fold (95% CI 1.18 to 2.33, p<0.005), but the risk was reduced after the first 4 years. Multivariable regression analyses revealed that aHR was 2.77-fold greater in patients not receiving disease-modifying anti-rheumatic drugs therapy than in non-RA subjects (p<0.05). Old age, women, low-income status and obesity could significantly predict NAFLD development. CONCLUSIONS: We demonstrated elevated risk of NAFLD in patients with RA during the first 4 years after RA diagnosis, and old age, women, low-income status and obesity were significant predictors of NAFLD.

SARS-CoV-2 primed platelets-derived microRNAs enhance NETs formation by extracellular vesicle transmission and TLR7/8 activation.

BACKGROUND: Hyperactive neutrophil extracellular traps (NETs) formation plays a key role in the pathogenesis of severe COVID-19. Extracellular vesicles (EVs) are vehicles which carry cellular components for intercellular communication. The association between COVID-19 patients-derived EVs and NETs formation remains elusive. METHODS: We explored the roles of EVs in NETs formation from 40 COVID-19 patients with different disease severities as well as 30 healthy subjects. The EVs-carried microRNAs profile was analyzed using next generation sequencing approach which was validated by quantitative reverse transcription PCR. The regulatory mechanism of EVs on NETs formation was investigated by using an in vitro cell-based assay, including immunofluorescence assay, flow cytometry, and immunoblotting. RESULTS: COVID-19 patient-derived EVs induced NETs formation by endocytosis uptake. SARS-CoV-2 spike protein-triggered NETs formation was significantly enhanced in the presence of platelet-derived EVs (pEVs) and this effect was Toll-like receptor (TLR) 7/8- and NADPH oxidase-dependent. Increased levels of miR-21/let-7b were revealed in EVs from COVID-19 patients and were associated with disease severity. We demonstrated that the spike protein activated platelets directly, followed by the subsequent intracellular miR-21/let-7b upregulation and then were loaded into pEVs. The pEVs-carried miR-21 interacted with TLR7/8 to prime p47phox phosphorylation in neutrophils, resulting in NADPH oxidase activation to promote ROS production and NETs enhancement. In addition, miR-21 modulates NF-κB activation and IL-1ß/TNFα/IL-8 upregulation in neutrophils upon TLR7/8 engagement. The miR-21 inhibitor and TLR8 antagonist could suppress efficiently spike protein-induced NETs formation and pEVs primed NETs enhancement. CONCLUSIONS: We identified SARS-CoV-2 triggered platelets-derived GU-enriched miRNAs (e.g., miR-21/let-7b) as a TLR7/8 ligand that could activate neutrophils through EVs transmission. The miR-21-TLR8 axis could be used as a potential predisposing factor or therapeutic target for severe COVID-19.

Subcutaneous Tocilizumab May Be Effective in Refractory Fibromyalgia Patients.

INTRODUCTION: Fibromyalgia (FM) is a chronic disorder characterized by widespread pain with an enormous symptom burden. Its treatment efficacy is limited. Its pathogenesis involves immune dysregulation, which includes interleukin-6 (IL-6) production. METHODS: We herein reported a case series of FM patients receiving subcutaneous tocilizumab at our institution. FM symptoms were evaluated by the revised Fibromyalgia Impact Questionnaire (FIQR), which included pain level, and the fibromyalgianess scale based on the 2016 criteria of the American College of Rheumatology (ACR). FM symptoms were compared using the Wilcoxon signed-rank test. Neutrophils from primary FM patients and matched healthy controls were also isolated for transcriptome analysis. RESULTS: We presented a total of two primary and four secondary FM patients who had received subcutaneous tocilizumab for a minimum of 12 weeks. All patients had severe symptoms despite standard treatments. Patients' FIQR and fibromyalgianess both dropped at 4 and 12 weeks. Four (67%) of them reached a pain reduction of ≥30% at 4 weeks, and three (50%) reached a pain reduction of ≥30% at 12 weeks. Possible differentially expressed genes were identified in primary FM patients when compared with controls and after tocilizumab treatment. CONCLUSIONS: FM patients likely benefited from subcutaneous tocilizumab therapy. A randomized controlled trial is needed to verify its efficacy.

The Sizes and Composition of HDL-Cholesterol Are Significantly Associated with Inflammation in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA), a chronic inflammatory disease, carries a significant burden of atherosclerotic cardiovascular diseases (ASCVD). With their heterogeneous composition, high-density lipoprotein (HDL) particles have varied athero-protective properties, and some may even increase ASCVD risk. In this prospective and cross-sectional study, we aimed to examine the relationship between HDL sizes/metabolites and inflammation in RA. Using 1H-NMR-based lipid/metabolomics, differential HDL-related metabolites were identified between RA patients and healthy control (HC) subjects and between RA patients with and without anti-citrullinated peptide antibodies (ACPA). The correlation between the discriminative HDL-related metabolites and C-reactive protein (CRP) was evaluated in RA patients. RA patients demonstrated higher particle number, lipids, cholesterol, cholesterol ester, free cholesterol, and phospholipids in large/very large-sized HDLs. ACPA-positive patients had higher L-HDL-C and L-HDL-CE but lower small-/medium-sized HDL-TG levels than ACPA-negative patients. An inverse correlation was found between CRP levels and small-sized HDLs. Janus kinase inhibitor treatment was associated with increased serum small-sized HDL-related metabolites and decreased CRP levels. We are the first to reveal the significant associations between RA inflammation and HDL sizes/metabolites. A potential link between ACPA positivity and changes in serum levels of HDL-related metabolites was also observed in RA patients.

CLEC18A Impairs Phagocytosis by Reducing FcγRIIA Expression and Arresting Autophagosome-Lysosome Fusion.

Mixed cryoglobulinemia (MC) is a hepatitis C virus (HCV)-related extrahepatic manifestation that is characterized by the abnormal presence of immune complexes (ICs). This may be due to the reduced uptake and clearance of ICs. The C-type lectin member 18A (CLEC18A) is a secretory protein that is expressed abundantly in hepatocytes. We previously observed that CLEC18A increased significantly in the phagocytes and sera of patients with HCV, particularly those with MC. Herein, we explored the biological functions of CLEC18A in the MC syndrome development of patients with HCV by using an in vitro cell-based assay with quantitative reverse transcription-PCR, immunoblotting, immunofluorescence, flow cytometry, and enzyme-linked immunosorbent assays. HCV infection or Toll-like receptor 3/7/8 activation could induce CLEC18A expression in Huh7.5 cells. Upregulated CLEC18A interacts with Rab5 and Rab7 and enhances type I/III interferon production to inhibit HCV replication in hepatocytes. However, overexpressed CLEC18A suppressed phagocytic activity in phagocytes. Significantly decreased levels of the Fc gamma receptor (FcγR) IIA were found in the neutrophils of HCV patients, particularly in those with MC (P < 0.005). We demonstrated that CLEC18A could inhibit FcγRIIA expression in a dose-dependent manner through the production of NOX-2-dependent reactive oxygen species to impair the uptake of ICs. Additionally, CLEC18A suppresses the Rab7 expression that is induced by starvation. Overexpressed CLEC18A does not affect autophagosome formation but does reduce the recruitment of Rab7 to autophagosomes, thereby retarding the maturation of autophagosomes and affecting autophagosome-lysosome fusion. We offer a novel molecular machinery with which to understand the association of HCV infection with autoimmunity and propose that CLEC18A may act as a candidate biomarker for HCV-associated MC. IMPORTANCE During infection, the host immune system produces cellular factors to protect against pathogen invasion. However, when the immune response overreacts and there is dysregulated cytokine homeostasis, autoimmunity occurs following an infection. We identified a cellular factor that is involved in HCV-related extrahepatic manifestation, namely, CLEC18A, which is expressed abundantly in hepatocytes and phagocytes. It inhibits HCV replication in hepatocytes by interacting with Rab5/7 and enhancing type I/III IFN expression. However, overexpressed CLEC18A inhibited FcγRIIA expression in phagocytes to impair phagocytosis. Furthermore, the interaction between CLEC18A and Rab5/7 may reduce the recruitment of Rab7 to autophagosomes and thereby retard autophagosome maturation and cause immune complex accumulation. A decreasing trend in CLEC18A levels that was accompanied by reduced HCV RNA titers and diminished cryoglobulin was observed in the sera of HCV-MC patients after direct-acting antiviral therapy. CLEC18A may be used for the evaluation of anti-HCV therapeutic drug effects and could be a potential predisposing factor for the development of MC syndrome.

Association of Hydroxychloroquine Use with a Dose-Dependent Decrease in Mortality Risk in Patients with Elderly-Onset Rheumatoid Arthritis.

INTRODUCTION: Elderly-onset rheumatoid arthritis (EORA) is associated with an increased mortality risk; however, the effect of conventional synthetic, biologics or targeted synthetic disease-modifying anti-rheumatic drugs (csDMARDs, bDMARDs or tsDMARDs) on the EORA-specific mortality risk is unknown. In this study, we investigated the risk factors for all-cause mortality of patients with EORA. METHODS: Data of EORA patients diagnosed with RA at age > 60 years between January 2007 and June 2021 were extracted from the electronic health record of Taichung Veterans General Hospital, Taiwan. Multivariable Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). The survival of patients with EORA was analyzed by Kaplan-Meier method. RESULTS: Among the 980 EORA patients who were enrolled (survivors 852 and non-survivor 128), the significant mortality-associated risk factors [HR (95% CI)] included higher age (1.10 [1.07-1.12], p < 0.001), male sex (1.92 [1.22-3.00], p = 0.004), current smoker (2.31 [1.10-4.87], p = 0.027) and underlying malignancy (1.89 [1.20-2.97], p = 0.006). Hydroxychloroquine treatment conferred protection against mortality in patients with EORA (HR 0.30, 95% CI 0.14-0.64, p = 0.002). Patients with malignancy who did not receive hydroxychloroquine treatment had the highest mortality risk compared with their counterparts. Patients with a monthly cumulative dose of hydroxychloroquine dose < 1374.5 mg had the lowest survival rate compared to patients who received hydroxychloroquine 1374.5-5778.5 and ≥ 5778.5 mg. CONCLUSION: Hydroxychloroquine treatment is associated with survival benefits in patients with EORA, and prospective studies are needed to validate the abovementioned findings.

The electronic medical record management systems may improve monitoring and control of disease activity in patients with ankylosing spondylitis.

To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p < 0.001), particularly among those with a high initial disease activity. The average visit time was reduced within 1 year after ASDAS assessment (6.4 (8.5, 11.2) vs. 6.3 (8.3, 10.8) min, p = 0.073), especially among patients whose with an inactive disease activity was < 1.3 (ASDAS C-reactive protein (CRP) 6.7 (8.8, 11.1) vs. 6.1 (8.0, 10.3) min, p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS.

The relationship between exposure to polycyclic aromatic hydrocarbons and adult atopic dermatitis.

BACKGROUND: Polycyclic aromatic hydrocarbons are one of the major pathogenic components in air pollution. Previous studies have demonstrated an association between air pollution and atopic dermatitis. OBJECTIVE: We sought to explore the relationship between polycyclic aromatic hydrocarbons exposure and adult atopic dermatitis. METHODS: We prospectively recruited 23 adult patients with atopic dermatitis and 11 healthy controls. Plasma levels of inflammatory cytokines were determined using enzyme-linked immunosorbent assay. Expression levels of aryl hydrocarbon receptor, which mediates the effect of polycyclic aromatic hydrocarbons, and cytokines in peripheral blood nuclear cells (PBMCs) were measured using reverse transcription polymerase chain reaction. Urine levels of 16 polycyclic aromatic hydrocarbon metabolites were determined by gas chromatography- tandem mass spectrometry. RESULTS: Patients with atopic dermatitis had lower levels of interleukin (IL)-5 and IL-23, and lower PBMC messenger RNA expression levels of interferon-> than the healthy controls. Plasma levels of IL-22 were moderately and positively associated with the SCORAD index. Creatinine-corrected urine levels of 9-hydroxyfluorene and 2-hydroxyphenanthrene were elevated in the atopic dermatitis group. However the difference was not statistically significant after Bonferroni correction. CONCLUSIONS: Our results demonstrated that the polycyclic aromatic hydrocarbons fluorene and phenanthrene are potentially associated with the pathogenesis of atopic dermatitis in adults.

TWEAK-Fn14 Axis Induces Calcium-Associated Autophagy and Cell Death To Control Mycobacterial Survival in Macrophages.

Autophagy is a natural defense mechanism that protects the host against pathogens. We previously demonstrated that mycobacterial infection upregulated tumor necrosis factor-like weak inducer of apoptosis (TWEAK) to promote autophagy and mycobacterial autophagosome maturation through activation of AMP-activated protein kinase (AMPK). Fibroblast growth factor-inducible 14 (Fn14) is the receptor of TWEAK. But the role of Fn14 in mycobacterial infection remains elusive. Herein, we observed increased expression of Fn14 in peripheral blood mononuclear cells of active tuberculosis (TB) patients. Downregulation of cellular Fn14 enhanced mycobacterial survival in macrophages. Conversely, Fn14 overexpression inhibited mycobacterial growth, suggesting that Fn14 can inhibit mycobacterial infection. The in vitro results revealed that TWEAK-promoted mycobacterial phagosome maturation is Fn14-dependent. We demonstrated that TWEAK-Fn14 signaling promotes oxidative stress to enhance the expression of stromal interaction molecule 1 (STIM1) and its activation of the Ca2+ channel ORAI1. Elevated calcium influx stimulated the activation of CaMCCK2 (calcium/calmodulin-dependent protein kinase kinase 2) and its downstream effector AMPK, thus inducing autophagy in early infection. Persistently TWEAK-Fn14 signaling caused cell death in late infection by reducing mitochondrial membrane potential, leading to mitochondrial ROS accumulation, and activating cell death-associated proteins. Genetic Fn14 deficiency or TWEAK blockers decreased oxidative stress-induced calcium influx, thus suppressing autophagy and cell death in mycobacteria-infected macrophages, and resulting in elevated mycobacterial survival. We propose that the TWEAK-Fn14 axis and calcium influx could be manipulated for anti-TB therapeutic purposes. Our results offer a new molecular machinery to understand the association between the TWEAK-Fn14 axis, calcium influx, and mycobacterial infection. IMPORTANCE Tuberculosis remains a major cause of morbidity and mortality worldwide. We previously demonstrated a relationship between TWEAK and activation of the autophagic machinery, which promotes anti-mycobacterial immunity. The TWEAK-Fn14 axis is multi-functional and involved in the pathogenesis of many diseases, thus blockade of TWEAK-Fn14 axis has been considered as a potential therapeutic target. Here, we demonstrated that the TWEAK-Fn14 axis plays a novel role in anti-mycobacterial infection by regulating calcium-associated autophagy. Persistently, TWEAK-Fn14 signaling caused cell death in late infection by reducing mitochondrial membrane potential, leading to mitochondrial ROS accumulation, and activating cell death-associated proteins. TWEAK blocker or Fn14 deficiency could suppress oxidative stress and calcium-associated autophagy, resulting in elevated mycobacterial survival. We propose that the TWEAK-Fn14 axis and calcium influx could be manipulated for anti-TB therapeutic purposes. This study offers a new molecular machinery to understand the association between the TWEAK-Fn14 axis, calcium influx, and mycobacterial infection.

Direct-Acting Antiviral Drugs Reduce Fibromyalgia Symptoms in Patients with Chronic Hepatitis C.

Background Fibromyalgia (FM) is a complex disorder characterized by chronic widespread pain and significant patient burden. Patients with chronic hepatitis C are reportedly predisposed to the development of FM. Direct-acting antiviral drugs (DAA) achieved a remarkable therapeutic efficacy in CHC patients. We therefore investigated the impact of DAA on FM symptoms in CHC patients. Methods We enrolled consecutive CHC patients who received DAA. FM symptoms were evaluated based on the 2016 American College of Rheumatology (ACR) fibromyalgia scale at baseline and 12 and 24 weeks after cessation of DAA therapy. Logistic regression was performed to determine the influence of HCV on FM at baseline. We also recruited individuals who underwent a health checkup examination as the control group, and calculated the standardized prevalence ratio of FM in CHC patients. Comparisons of fibromyalgia in different time points were undertaken using the Wilcoxon signed-rank test. Results A total of 33 CHC patients (15 males and 18 females) and 402 controls were recruited. All CHC patients achieved sustained virological response. Two (6%) patients and two (0.5%) controls fulfilled the diagnostic criteria for FM, and the standardized prevalence ratio was 23.9 in CHC patients. Logistic regression also showed increased odds for FM in CHC patients after adjusting for age and sex (OR: 14.4; 95%CI: 1.6, 128.0). In addition, their fibromyalgianess scale decreased at 12 and 24 weeks after DAA therapy. In conclusion, CHC patients were more likely to develop FM. Implementation of DAA therapy might improve FM symptoms in these patients.

The association between hydroxychloroquine use and future development of systemic lupus erythematosus in patients with primary Sjögren's syndrome.

AIM: Hydroxychloroquine (HCQ), commonly used to treat patients with primary Sjögren's syndrome (pSS), has been shown to delay the development of systemic lupus erythematosus (SLE). This study aimed to explore the association between HCQ use and future development of SLE in pSS patients based on a nationwide nested case-control study. METHOD: Based on the National Health Insurance Research Database of Taiwan, those patients who were diagnosed with SLE at least 1 year after the diagnosis of pSS were identified as cases. Matched controls were randomly selected from pSS patients without a later diagnosis of SLE in a 1:10 ratio. The odds ratios (ORs) of HCQ exposure between cases and controls were analyzed by unconditional logistic regression after adjustment for age. RESULTS: A cohort of 11 772 pSS patients were extracted from the database during the period from January 1, 2000 to December 31, 2010. A total of 111 (0.9%) pSS patients developed SLE during the follow-up period. Most (79%) of them developed SLE within 5 years after the diagnosis of pSS. There was no significant difference in the odds of HCQ exposure between cases and controls, with an adjusted OR of 2.43 (95% CI: 0.73-8.05). Neither did we observe a significant difference in the odds of exposure to a higher average dose of HCQ (≥100 mg/d vs non-exposed) between cases and controls in the sensitivity analysis. CONCLUSION: Nearly 1% of pSS patients may develop SLE. HCQ use in pSS patients was not associated with a lower possibility of the future development of SLE.

Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases.

Objectives: To investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq). Methods: From September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis. Results: The anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (ß: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group. Conclusions: mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.

The BASDAI Cut-Off for Disease Activity Corresponding to the ASDAS Scores in a Taiwanese Cohort of Ankylosing Spondylitis.

Objectives: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been widely utilized to evaluate disease activity in patients with ankylosing spondylitis (AS) by an arbitrary cut-off of ≥4 to indicate high disease activity and initiate biological therapy. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess AS disease activity states that have been defined and validated. ASDAS ≥2.1 was selected as a criterion to start biological therapy. The purpose of this study was to estimate the corresponding BASDAI and ASDAS cut-off in a Taiwanese AS cohort. Methods: From November 2016 to October 2018, we assessed the ASDAS and the BASDAI regularly and recorded demographic data for 489 AS patients in Taichung Veterans General hospital (TCVGH) using an electronic patient-reported data system linked to electronic medical records. We used receiver operating characteristic curves with Youden's J statistic to determine the BASDAI values that correspond to ASDAS disease activity cut-offs (i.e., 1.3, 2.1, and 3.5). Results: In our population, the best trade-off BASDAI values corresponding to ASDAS -C-reactive protein (CRP) 1.3, 2.1, and 3.5 were 2.1, 3.1, and 3.7, respectively. The optimal BASDAI values corresponding to ASDAS-erythrocyte sedimentation rates 1.3, 2.1, and 3.5 were 2.0, 2.6, and 4.8, respectively. Conclusion: We propose a revised BASDAI cut-off based on our data, as BASDAI scores are commonly used globally. A more reasonable, lower BASDAI cut-off to initiate or change biological therapy will bring us closer to better decisions to treat AS patients.