Integrative Systems Immunology Analysis Reveals Elevated Anti-AGTR1 Levels with Accumulating COVID-19 Symptoms (preprint)

The coronavirus disease 2019 (COVID-19) displays a broad spectrum of symptoms, with the underlying reasons for this variability still not fully elucidated. Our study investigates the potential association between specific autoantibodies (AABs), notably those that targeting G protein-coupled receptors (GPCRs) and renin-angiotensin system (RAS) related molecules, and the diverse clinical manifestations of COVID-19, commonly observed in patients with autoimmune conditions, including rheumatic diseases, such as systemic sclerosis. In a cross-sectional analysis, we explored the relationship between AAB levels and the presence of key COVID-19 symptoms. Hierarchical clustering analysis revealed a robust correlation between certain AABs and symptoms such as fever, muscle ache, anosmia, and dysgeusia, which emerged as significant predictors of disease severity. Specifically, AABs against CHRM5 and CXCR3 were strongly linked to fever, while AABs against CHRM5 and BDKRB1 correlated with muscle ache. Anosmia was predominantly associated with AABs against F2R and AGTR1, while dysgeusia was linked to AABs against BDKRB1 and AGTR1. Furthermore, we observed a rise in AAB levels with the accumulation of these symptoms, with the highest levels detected in patients presenting all four predictors. Multinomial regression analysis identified AABs targeting AGTR1 as a key predictor for one or more of these core symptoms. Additionally, our study indicated that anti-AGTR1 antibodies triggered a concentration-dependent degradation of eGC, which could be mitigated by the AGTR1 antagonist Losartan. This suggests a potential mechanistic connection between eGC degradation, the observed COVID-19 symptoms, and rheumatic diseases. In conclusion, our research underscores a substantial correlation between AABs, particularly those against GPCRs and RAS-related molecules, and the severity of COVID-19 symptoms. These findings open avenues for potential therapeutic interventions in the management of COVID-19.

COVID-19 Impact on Patients with Immune-Mediated Rheumatic Disease: A Comparative Study of Disease Activity and Psychological Well-Being Over Six Months (preprint)

Objectives: To compare the impact of COVID-19 on clinical status and psychological condition in patients with immune-mediated rheumatic diseases (IMRD) infected by SARS-CoV-2 with IMRD controls not infected, during a 6-month follow-up. Methods: The ReumaCoV Brasil is a longitudinal study designed to follow-up IMRD patients for 6 months after COVID-19 (cases) compared with IMRD patients no COVID-19 (controls). Clinical data, disease activity measurements and current treatment regarding IMRD, and COVID-19 outcomes were evaluated in all patients. Disease activity was assessed through validated tools at inclusion and at 3 and 6 months post-COVID-19. The FACIT-F (Functional Assessment of Chronic Illness Therapy) and DASS 21 (Depression, Anxiety and Stress Scale - 21 Items) questionnaires were also applied at 6 months after COVID-19 in both groups before large-scale vaccination. The significance level was set as p<0.05, with a 95% confidence interval. Results: A total of 601 patients were evaluated, being 321 cases (IMRD COVID-19+) and 280 controls (IMRD COVID-19 -), predominantly female with similar median age. No significant differences were noted in demographic data between the groups, including comorbidities, disease duration, and IMRD. Disease activity assessment over a 6-month follow-up showed no significant difference between cases and controls. While mean activity scores did not differ significantly, some patients reported worsened disease activity post-COVID-19, particularly in rheumatoid arthritis (RA) (32.2%) and systemic lupus erythematosus (SLE) (23.3%). Post-COVID-19 worsening in RA patients correlated with medical global assessment (MGA) and CDAI scores, with a moderate to large effect size. Diabetes mellitus showed a positive association (OR=7.15), while TNF inhibitors showed a protective effect (OR=0.51). Comparing SLEDAI pre- and post-COVID-19, a minority showed increased scores, with few requiring treatment changes. Fatigue, depression, anxiety, and stress were significantly higher in cases compared to controls. Worsening disease activity post-COVID correlated with worsened FACIT-F and DASS-21 stress scale in RA patients. No significant associations were found between COVID-19 outcomes and post-COVID-19 disease activity or psychological assessments. Conclusions: Post-COVID-19 IMRD patients show significant psychological well-being deterioration despite similar disease activity scores. The variability in reports on IMRD flares and the potential trigger of SARS-CoV-2 for autoimmune manifestations underline the need for detailed clinical assessment and a comprehensive approach to managing them.

Influence of the COVID-19 Pandemic on the Treatment of immune mediated Rheumatic and Musculoskeletal Diseases during the first pandemic period: A Systematic Review (preprint)

Background and Objectives: The COVID-19 pandemic influenced the management of patients with immune mediated rheumatic and musculoskeletal diseases (imRMDs) in various ways. The goal of our systematic review was to determine the influence of the first period of the COVID-19 pandemic on the management of imRMDs. Materials and Methods: Systematic literature search of PubMed, Cochrane and Embase databases, including studies with adult patients on the influence of the COVID-19 pandemic on management of imRMDs. There were no restrictions regarding to study-design except for systematic reviews and case reports that were excluded as well as articles on the disease outcomes in case of SARS-CoV-2 infection. Two reviewers screened the studies for inclusion, and, in case of disagreement, consensus was reached after discussion. Results: A total of 5969 potentially relevant studies were found, and, after title, abstract and full-text screening, 35 studies were included with data from 182’746 patients and 2018 rheumatologists. Non-availability of drugs, e.g., hydroxychloroquine and tocilizuab, was frequent (16–69% of patients). Further, medication non-adherence was reported among patients with different RMDs and between different drugs in 4–46% of patients. Changes to preexisting medication were reported in up to 33% of patients (e.g. reducing dose of steroids or cessation of biological disease-modifying antirheumatic drugs). Physical in-office consultations and laboratory testing decreased and as a consequence newly implemented remote consultations increased greatly with an increase of up to 80%. Conclusion: The COVID-19 pandemic influenced the management of imRMDs, especially at the beginning. Influences were wide-ranging, affecting availability of pharmacies, adherence to medication or medication changes, doctor visits and laboratory testing. New systems of care were set up, including virtual clinics and video consultations. These new forms of health care delivery should be spread and implemented worldwide to routine clinical practice to be ready for future pandemics.

Safety and Efficacy of Tixagevimab and Cilgavimab for Prophylaxis of Covid-19 in a Cohort of Immunosuppressed Rheumatic Patients Treated with Rituximab: A Real-Life Experience (preprint)

(1) Background: Immunosuppressed patients, especially those receiving B-cells depleting therapies (BCDT), are at major risk to develop reduced vaccine seroconversion and contract severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. The aim of our study is to assess safety and efficacy of the pre-exposure prophylactic combination of Tixagevimab and Cilgavimab (TGM-CGM) in a cohort of rheumatic patients diagnosed with Autoimmune Rheumatic Diseases; (2) Methods: We performed a prospective study using the clinical medical charts of 25 patients treated with Rituximab and received a single injection of TGM/CGM. The cohort was followed for 6 months from the injection and compared to a control group of 25 immunosuppressed patients who did not receive TGM-CGM. We assessed the incidence and the severity of Covid-19 in both groups, as well as early and late adverse events; (3) Results: Despite the small sample, we noticed a downward trend in the incidence and severity of symptomatic infection in the group treated with TGM/CGM. In the experimental cohort, one patient was completely asymptomatic, four patients were oligosymptomatic infection, and just one had mild-moderate infection versus 4 oligosymptomatic and 5 mild-moderate infection in the control group. We observed also a reduction in time to nasopharyngeal swab negativization. No adverse events were reported in our data. We collected the dosage of anti-Receptor-Binding Domain (RBD) SARS-CoV2 spike protein for 21 patients, revealing adequate seroconversion in 12 patients out of 21; (4) Conclusions: Even though the study was conducted during the Omicron wave, notably known to be less responsive to monoclonal antibodies, we proved that TGM-CGM could be a risk-free additional tool to prevent SARS-Cov2 infection in rheumatic immunosuppressed patients.

Impact of the COVID-19 pandemic on outpatient appointments of rheumatic patients in a low- and medium-risk area of China (preprint)

Background We aimed to determine the impact of different strategies of outpatient appointments of rheumatic patients in a low- and medium-risk area of China against the COVID-19 pandemic.Methods Three hospitals in Shandong Province were investigated to compare the number of outpatient appointments of rheumatic patients before and after the COVID-19 pandemic.Results The number of outpatient appointments of rheumatic patients in 2020 decreased significantly under strict restrictive COVID-19 prevention measures compared to prior to the pandemic. The impact on Western medicine hospitals was greater than that on a traditional Chinese medicine (TCM) hospital. After COVID-19, first-level public health emergency responses were degraded, and the number of outpatient appointments increased rapidly, exceeding the numbers in 2019 before the COVID-19 pandemic.Conclusion In the early stage of the pandemic, severe restrictive policies were effective measures in limiting the spread of COVID-19, but outpatient appointments in the three hospitals were significantly affected. The impacts on these three hospitals were different, with the designated Western medicine hospital for COVID-19 treatment suffering the greatest impact.

Clinical Features of COVID-19 in Pediatric Rheumatic Diseases: 2020-2022 Survey of the Pediatric Rheumatology Association of Japan.

Coronavirus disease 2019 (COVID-19) in children can be compounded by concurrent diseases and immunosuppressants. For the first time, we aimed to report the clinical features of concurrent COVID-19 and pediatric rheumatic disease (PRD) in Japan. Pediatric Rheumatology Association of Japan members were surveyed between 1 April 2020 and 31 August 2022. Outcome measurements included the clinical features of concurrent PRD and COVID-19. Questionnaire responses were obtained from 38 hospitals. Thirty-one hospitals (82%) had children with PRD and COVID-19. The female-to-male ratio in these children (n = 156) was 7:3, with half aged 11-15 years. The highest proportion of children with PRD and COVID-19 was accounted for by juvenile idiopathic arthritis (52%), followed by systemic lupus erythematosus (24%), juvenile dermatomyositis (5%), scleroderma (4%), and Takayasu arteritis (3%). Of children with PRD, a significant majority (97%) were found to be asymptomatic (10%) or presented with mild symptoms (87%) of the COVID-19 infection. No severe cases or deaths were observed. Regarding the use of glucocorticoids, immunosuppressants, or biologics for PRD treatment before COVID-19, no significant difference was found between asymptomatic/mild and moderate COVID-19 in children with PRD. Therefore, COVID-19 is not a threat to children with PRD in Japan.

Post-acute COVID-19 in three doses vaccinated autoimmune rheumatic diseases patients: frequency and pattern of this condition.

BACKGROUND: Data on post-acute COVID-19 in autoimmune rheumatic diseases (ARD) are scarce, focusing on a single disease, with variable definitions of this condition and time of vaccination. The aim of this study was to evaluate the frequency and pattern of post-acute COVID-19 in vaccinated patients with ARD using established diagnosis criteria. METHODS: Retrospective evaluation of a prospective cohort of 108 ARD patients and 32 non-ARD controls, diagnosed with SARS-CoV-2 infection (RT-PCR/antigen test) after the third dose of the CoronaVac vaccine. Post-acute COVID-19 (≥ 4 weeks and > 12 weeks of SARS-CoV-2 symptoms) were registered according to the established international criteria. RESULTS: ARD patients and non-ARD controls, balanced for age and sex, had high and comparable frequencies of ≥ 4 weeks post-acute COVID-19 (58.3% vs. 53.1%, p = 0.6854) and > 12 weeks post-acute COVID-19 (39.8% vs. 46.9%, p = 0.5419). Regarding ≥ 4 weeks post-acute COVID-19, frequencies of ≥ 3 symptoms were similar in ARD and non-ARD controls (54% vs. 41.2%, p = 0.7886), and this was also similar in > 12 weeks post-acute COVID-19 (68.3% vs. 88.2%, p = 0.1322). Further analysis of the risk factors for ≥ 4 weeks post-acute COVID-19 in ARD patients revealed that age, sex, clinical severity of COVID-19, reinfection, and autoimmune diseases were not associated with this condition (p > 0.05). The clinical manifestations of post-acute COVID-19 were similar in both groups (p > 0.05), with fatigue and memory loss being the most frequent manifestations. CONCLUSION: We provide novel data demonstrating that immune/inflammatory ARD disturbances after third dose vaccination do not seem to be a major determinant of post-acute COVID-19 since its pattern is very similar to that of the general population. Clinical Trials platform (NCT04754698).

Humoral immunogenicity of COVID-19 vaccines in patients with inflammatory rheumatic diseases under treatment with Rituximab: a case-control study (COVID-19VacRTX).

OBJECTIVES: Patients with inflammatory rheumatic diseases (IRDs) treated with the anti-CD20 mAb rituximab (RTX) have been identified as high-risk for severe COVID-19 outcomes. Additionally, there is increased risk due to reduced humoral immune response, induced by therapeutic B cell depletion. This study sought to quantify humoral response after vaccination against SARS-CoV-2 in patients with IRD treated with RTX. It also sought to elucidate the influence of the time frame between the last RTX dose and the first vaccination, or the status of B cell depletion on antibody titre. METHODS: In this case-control study, patients with IRDs previously treated with RTX were examined for humoral immune response after completing the first series of vaccinations with approved vaccines [BNT162b2 (Biontech/Pfizer), RNA-1273 (Moderna), AZD1222 (AstraZeneca/Oxford), Ad26.COV2.S (Janssen/Johnson & Johnson)]. Antibody levels were quantified using the Euroimmun Anti-SARS-CoV-2 QuantiVac ELISA (EI-S1-IgG-quant). Blood samples were taken just before the next infusion with RTX after the vaccination. The interval between the last RTX infusion and the first vaccination against SARS-CoV-2 and other possible factors influencing the antibody levels were evaluated. RESULTS: A total of 102 patients were included. Of these, 65 (64%) showed a negative antibody level (<24 IU (international unit)/ml) after the vaccination. The comparative univariate analysis of the antibody levels achieved a significant result (P = 0.0008) for the time between the last RTX infusion and first vaccination against SARS-CoV-2. No CD19+ peripheral B-cells could be detected in 73 of the patients (72%). CONCLUSION: The study confirms the negative impact of RTX on antibody level after vaccination against SARS-CoV-2. A clear relationship exists between the antibody titre and the interval between the last RTX infusion and the first vaccination, the number of peripheral B-cells, and immunoglobulin quantity. Improved understanding of the effect of these parameters can help guide synchronization of vaccination in relation to the RTX therapy regimen.

Axial spondylarthritis following COVID-19 infection.

Although SARS-CoV-2 syndrome primarily affects the lungs, systemic manifestations have been reported. New rheumatic immune-mediated inflammatory diseases have been reported following SARS-CoV-2 infection. We present a case of a woman in her mid-30s who developed inflammatory back pain due to bilateral sacroiliitis with erosions after contracting SARS-CoV-2 infection. Her inflammatory markers on presentation were normal. MRI of the sacroiliac joints demonstrated bone marrow oedema and erosive changes in both sacroiliac joints. As the patient was intolerant to non-steroidal anti-inflammatory drugs, adalimumab 40 mg subcutaneous (SC) injection was administered, which improved her symptoms in 8 weeks. However, due to the drug's side effects, SC adalimumab was switched to intravenous infliximab. The patient is currently tolerating her intravenous infliximab well and has experienced significant improvement in her symptoms. We reviewed the current literature on the prevalence of axial spondyloarthropathy after SARS-CoV-2 infection.

Immunogenicity of COVID-19 vaccines in adult patients with autoimmune inflammatory rheumatic diseases: A systematic review and meta-analysis.

COVID-19 vaccines approved by the Food and Drug Administration have been studied mainly in healthy individuals and there is limited information on their immunogenicity in patients with autoimmune diseases. Therefore, the current systematic review and meta-analysis study, aimed to comprehensively investigate the immunogenicity of these vaccines in patients with autoimmune inflammatory rheumatoid diseases (AIRDs). A comprehensive literature search was performed on various databases, including Google Scholar, PubMed, Web of Science, EMBASE, and Cochrane Library, to select cohort and randomized clinical trial (RCT) studies up to January 2022. Also, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist protocol and the I2 statistic were used for quality assessment and heterogeneity tests of the selected studies. Fixed and random-effects models were estimated based on the heterogeneity tests, and pooled data were determined as the ratio of mean (ROM) with a 95% confidence interval (CI). As a result, we found that vaccines can cause favorable immunogenicity and antibody response in vaccinated AIRD patients; however, older age and the concomitant consumption of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biologic DMARDs (bDMARDs) could significantly reduce the vaccine immunogenicity. Consequently, our findings revealed significant humoral responses (seropositive) in AIRD patients following the administration of COVID-19 vaccines.

The development of anti-cyclic citrullinated peptide (Anti-CCP) antibody following severe COVID-19 (preprint)

The dysregulated immune response is one of the cardinal features of severe coronavirus disease-2019 (COVID-19). This study has been conducted to clarify the occurrence of AABs associated with a systemic autoimmune rheumatic disease (SARD) in hospitalized patients with a moderate, severe, and critical form of COVID-19. The serum samples obtained from one hundred seventy-six hospitalized COVID-19 patients were enrolled in this study, including patients with moderate (N = 90), severe (N = 50), and critical (N = 36) forms of COVID-19. Serum samples collected from healthy subjects before the COVID-19 pandemic were used as control. The ANA, ds-DNA, c-ANCA, p-ANCA, aPL, and anti-CCP occurrence was evaluated using a solid-phase enzyme-linked immunosorbent assay (ELISA). The occurrence of ANA, anti-dsDNA, Anti-CCP, c-ANCA, and p-ANCA was significantly higher in the COVID-19 patients compared to serum obtained from healthy subjects (P = 0.0001, P = 0.0001, P = 0.0001, P = 0.030, and P = 0.001 respectively). The positive number of anti-CCP tests increased significantly in severe COVID-19 compared to the moderate group (P = 0.002). Our study further supports the development of autoantibodies related to systemic autoimmune rheumatologic diseases (SARD). To the best of our knowledge, this is the first study with a large sample size that reported the occurrence of anti-CCP in a severe form of COVID-19.

Efficacy and safety of mRNA and AstraZeneca COVID-19 vaccines in patients with autoimmune rheumatic diseases: A systematic review.

BACKGROUND: Patients with autoimmune rheumatic diseases (ARD) are at a potentially higher risk for COVID-19 infection complications. Given their inherent altered immune system and the use of immunomodulatory medications, vaccine immunogenicity could be unpredictable with a suboptimal or even an exaggerated immunological response. The aim of this study is to provide real-time data on the emerging evidence of COVID-19 vaccines' efficacy and safety in patients with ARDs. METHODS: We performed a literature search of the PubMed, EMBASE, and OVID databases up to 11-13 April 2022 on the efficacy and safety of both types of the mRNA-vaccines and the AstraZeneca COVID-19 vaccines in patients with ARD. The risk of bias in the retrieved studies was evaluated using the Quality in Prognostic Studies tool. Also, current clinical practice guidelines from multiple international professional societies were reviewed. RESULTS: We identified 60 prognostic studies, 69 case reports and case series, and eight international clinical practice guidelines. Our results demonstrated that most patients with ARDs were able to mount humoral and/or cellular responses after two doses of COVID-19 vaccine although this response was suboptimal in patients receiving certain disease-modifying medications including rituximab, methotrexate, mycophenolate mofetil, daily glucocorticoids >10 mg, abatacept, as well as in older individuals, and those with comorbid interstitial lung diseases. Safety reports on COVID-19 vaccines in patients with ARDs were largely reassuring with mostly self-limiting adverse events and very minimal post-vaccination disease flares. CONCLUSION: Both types of the mRNA-vaccines and the AstraZeneca COVID-19 vaccines are highly effective and safe in patients with ARD. However, due to their suboptimal response in some patients, alternative mitigation strategies such as booster vaccines and shielding practices should also be followed. Management of immunomodulatory treatment regimens during the peri vaccination period should be individualized through shared decision making with patients and their attending rheumatologists.

Disease relapse rate in children with autoimmune rheumatic diseases after COVID-19 infection and vaccination.

BACKGROUND: Paediatric patients with autoimmune rheumatic diseases (pARD) are often immunocompromised because of the disease and/or the therapy they receive. At the beginning of COVID-19 pandemic there was a great concern about the possibility of severe SARS-CoV-2 infection in these patients. The best method of protection is vaccination, so as soon as vaccine was licenced, we aimed to vaccinate them. Data on disease relapse rate after COVID-19 infection and vaccination are scarce, but they play important role in everyday clinical decisions. METHODS: The aim of this study was to determine the relapse rate of autoimmune rheumatic disease (ARD) after COVID-19 infection and vaccination. Data on demographic, diagnosis, disease activity, therapy, clinical presentation of the infection and serology were collected from pARD who had COVID-19 and from pARD who were vaccinated against COVID-19, from March 2020 to April 2022. All vaccinated patients received two doses of the BNT162b2 BioNTech vaccine, on average, 3.7 (S.D.=1.4) weeks apart. Activity of the ARD was followed prospectively. Relapse was defined as a worsening of the ARD in a time frame of 8 weeks after infection or vaccination. For statistical analysis, Fisher's exact test and Mann-Whitney U test were used. RESULTS: We collected data from 115 pARD, which we divided into two groups. We included 92 pARD after infection and 47 after vaccination, with 24 in both groups (they were infected before/after vaccination). In 92 pARD we registered 103 SARS-CoV-2 infections. Infection was asymptomatic in 14%, mild in 67% and moderate in 18%, 1% required hospitalization; 10% had a relapse of ARD after infection and 6% after vaccination. There was a trend towards higher disease relapse rate after infection compared to vaccination, but the difference was not statistically significant (p = 0.76). No statistically significant difference was detected in the relapse rate depending on the clinical presentation of the infection (p = 0.25) or the severity of the clinical presentation of COVID-19 between vaccinated and unvaccinated pARD (p = 0.31). CONCLUSIONS: There is a trend towards a higher relapse rate in pARD after infection compared to vaccination and connection between the severity of COVID-19 and vaccination status is plausible. Our results were, however, not statistically significant.

COVID-19 and flu, exploring the infection of virus, the safety and attitudes of vaccination in pediatric patients with rheumatic diseases (preprint)

Background Patients with rheumatic diseases have an increased burden of infections. Immunization is recognized as being one of the most efficient means to prevent infections. However, many patients refuse or hesitate to be vaccinated mainly due to safety concerns. We performed this study to explore the infection of COVID-19 and influenza, the safety and attitudes regarding inactivated COVID-19 vaccination and influenza vaccination in pediatric rheumatic patients.Methods We conducted a retrospective survey using a questionnaire from November 1, 2021 to February 28, 2022. Pediatric rheumatic patients with inactive disease received inactivated COVID-19 vaccine at the age of 3–18 years old were recruited. Demographic data and vaccination adverse events (AEs) were collected. All parents of patients were telephone-interviewed in May 2023 regarding COVID-19 infection, influenza infection and influenza vaccination of their children in the past one year. Self-reported disease flares that occurred after infection and vaccination, as well as reasons for non-vaccination were recorded.Results A total of 192 patients were recruited. Local AEs occurred in 11.5% and 10.1% of patients after the first and the second dose of COVID-19 vaccination; the percentages were 8.9% and 6.3% for systemic AEs. Three (1.6%) patients experienced original disease flare. In total, 177 parents responded the telephone questionnaire, among which, 101 (57.1%) of their children had COVID-19 infection. All had mild symptoms and 8 patients experienced disease flares. Thirty-two (18.1%) patients had influenza infection. All experienced mild symptoms except one patient was hospitalization. One patient experienced a disease flare. Seventeen (9.6%) patients were vaccinated against influenza, none of them experienced serious AEs or disease flare. The main reasons for non-vaccination of influenza were the fear of AEs and disease flare (n = 60, 37.5%) and not receiving enough information about influenza vaccination from their doctors (n = 84, 52.5%). Ninety-six (60%) parents whose children were non-vaccination responded that would vaccinate their children if advised to by a rheumatologist.Conclusions These findings confirm on the safety of inactivated COVID-19 vaccination and inactivated influenza vaccination in pediatric rheumatic patients. Rheumatologists should take more responsibility in vaccination education of pediatric rheumatic patients.

Tracking clinical resources for coronavirus disease 2019.

PURPOSE OF REVIEW: Assimilating and disseminating information during the novel coronavirus disease 2019 (COVID-19) has been challenging. The purpose of this review is to identify specific threats to the validity of the COVID-19 literature and to recommend resources for practicing rheumatologists and their patients. RECENT FINDINGS: The COVID-19 literature has rapidly expanded and includes 17 998 publications through May of 2020, 1543 of which also address rheumatic disease-related topics. Specific obstacles to acquiring high-quality information have arisen, including 'pandemic research exceptionalism' and a 'parallel pandemic' of misinformation. Unique challenges to rheumatologists include specific interest in antirheumatic disease therapies and a paucity of rheumatology-specific information. Patients with rheumatic diseases have faced shortages of critical medications and a lack of information tailored to their health conditions and medications. SUMMARY: We recommend rheumatologists develop a system to acquire high-quality information and offer guiding principles for triaging specific resources, which include relevance, accessibility, credibility, timeliness, and trustworthiness. The same principles can be applied to selecting patient oriented resources. Specific trustworthy resources are recommended.

Translating IL-6 biology into effective treatments.

In 1973, IL-6 was identified as a soluble factor that is secreted by T cells and is important for antibody production by B cells. Since its discovery more than 40 years ago, the IL-6 pathway has emerged as a pivotal pathway involved in immune regulation in health and dysregulation in many diseases. Targeting of the IL-6 pathway has led to innovative therapeutic approaches for various rheumatic diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still's disease, giant cell arteritis and Takayasu arteritis, as well as other conditions such as Castleman disease and cytokine release syndrome. Targeting this pathway has also identified avenues for potential expansion into several other indications, such as uveitis, neuromyelitis optica and, most recently, COVID-19 pneumonia. To mark the tenth anniversary of anti-IL-6 receptor therapy worldwide, we discuss the history of research into IL-6 biology and the development of therapies that target IL-6 signalling, including the successes and challenges and with an emphasis on rheumatic diseases.

COVID-19 Vaccination Perceptions in Patients With Rheumatic Disease: A Cross-Sectional Online Survey.

OBJECTIVE: To identify the factors that affect coronavirus disease 2019 (COVID-19) vaccine decision making among individuals diagnosed with a rheumatologic condition, given that previous international studies have demonstrated that a significant proportion of patients with rheumatic disease (RD) are vaccine hesitant. METHODS: This cross-sectional study involved an online survey with adult patients with RD from the Kaye Edmonton Clinic Rheumatology Clinic between June and August 2021. Quantitative results were descriptively analyzed, whereas qualitative thematic analysis was conducted for open-ended responses. RESULTS: The survey had a response rate of 70.9% (N = 231). Regarding COVID-19 vaccines, patients with RD were most concerned about the possible effect of vaccination on their rheumatic condition (45.2%) and about vaccine effectiveness (45.1%). Most patients had discussed COVID-19 vaccination (75.9%) and its risks and benefits (66.1%) with their medical team, and 83.6% of respondents were confident in the information provided. Patients' perceptions of the government's role in handling the COVID-19 pandemic varied: 33% reported that they found government-instituted public health measures effective. Surprisingly, 9.7% of patients with RD still reported concerns that they could develop COVID-19 from an approved COVID-19 vaccine. CONCLUSION: This study describes factors implicated in COVID-19 vaccine decision making among patients with RD. Three important themes included possible adverse effects of the vaccine on RD control, reduced vaccine efficacy because of RD/treatment, and risk of contracting SARS-CoV-2 from the COVID-19 vaccine. Knowledge from this study can assist healthcare providers in looking after patients with RD to initiate discussions with patients to share evidence-based vaccine information and assist with informed decision making.

Sociocultural and moral narratives influencing the decision to vaccinate among rheumatic disease patients: a qualitative study.

INTRODUCTION/OBJECTIVES: Vaccination is a process that involves individual, social, and ethical aspects, beyond public governance of vaccines or vaccination as a public health concern. The aim of this study is to describe the sociocultural and moral narratives that influence the decision to vaccinate in general and to vaccinate against COVID-19 specifically, among patients at the rheumatology units of two hospitals. METHODS: Qualitative study involving individual semi-structured interviews following an interview guide. We conducted a thematic analysis using the ATLAS.ti software, with further triangulation to verify concordance and aid in the interpretation of the data from a medical anthropology framework and using a narrative ethics approach to gain insight into the participants' underlying moral values. RESULTS: We interviewed 37 patients in total, along with 3 rheumatologists. Five core themes emerged from the analysis to understand the decision to vaccinate: (1) information about vaccines and disease, (2) perceived risk-benefit of vaccination, (3) the physician-patient relationship, (4) governance of vaccination programs, (5) attitudes towards vaccines. Individual and family experiences with vaccination are diverse depending on the type of vaccine. The COVID-19 vaccine, as a new medical technology, is met with more controversy leading to hesitancy. CONCLUSIONS: The decision to vaccinate among Mexican rheumatic disease patients can sometimes involve doubt and distrust, especially for those with a lupus diagnosis, but ultimately there is acceptance in most cases. Though patients make and value autonomous decisions, there is a collective process involving sociocultural and ethical aspects. Key points • The complexity of vaccine decision-making is better identified through a narrative, qualitative approach like the one used in this study, as opposed to solely quantitative approaches • Sociocultural and moral perspectives of vaccination shape decision-making and, therefore, highlight the importance of including patients in the development of effective clinical practice guidelines as well as ethically justified public policy • Sociohistorical context and personal experiences of immunization influence vaccine decision-making much more than access to biomedical information about vaccines, showing that approaches based on the information deficit model are inadequate to fight vaccine hesitancy.