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.

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.

The COVID-19 epidemic curve and vaccine acceptance among patients with rheumatic diseases: an ecological study.

The attitudes toward emerging COVID-19 vaccines have been of great interest worldwide, especially among vulnerable populations such as patients with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to analyze the relationship between the nationwide number of COVID-19 cases and deaths, and vaccine acceptance or hesitancy of patients with RMDs from four patient care centers in Mexico. Furthermore, we explored differences in acceptance according to specific diagnoses: rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This ecological study was a secondary analysis of a cross-sectional study using a validated questionnaire to measure vaccine acceptance. We generated a global Likert scale to evaluate overall attitudes toward the COVID-19 vaccine. We analyzed data from 1336 patients from March to September 2021: 85.13% (1169) were women, with a mean age of 47.87 (SD 14.14) years. The most frequent diagnoses were RA (42.85%, 559) and SLE (27.08%, 393). 635(47.52%) patients were unvaccinated, 253(18.93%) had one dose and 478(35.77%) had two doses. Of all participating patients, 94% were accepting toward the COVID-19 vaccine. Vaccine acceptance remained consistently high throughout the study. However, differences in vaccine acceptance are identified when comparing diagnoses. The peak of the national epidemic curve coincided with an increase in hesitancy among patients with RA. Contrastingly, patients with SLE became more accepting as the epidemic curve peaked. Mexican patients show high acceptance of the COVID-19 vaccine, influenced in part by a patient's specific diagnosis. Furthermore, vaccine acceptance increased mirroring the curve of COVID-19 cases and deaths in the country. This should be taken into consideration when updating recommendations for clinical practice.

Characteristics and outcomes of SARS-CoV-2 breakthrough infections among double-vaccinated and triple-vaccinated patients with inflammatory rheumatic diseases.

OBJECTIVE: To analyse the clinical profile of SARS-CoV-2 breakthrough infections in at least double-vaccinated patients with inflammatory rheumatic diseases (IRDs). METHODS: Data from the physician-reported German COVID-19-IRD registry collected between February 2021 and July 2022 were analysed. SARS-CoV-2 cases were stratified according to patients' vaccination status as being not vaccinated, double-vaccinated or triple-vaccinated prior to SARS-CoV-2 infection and descriptively compared. Independent associations between demographic and disease features and outcome of breakthrough infections were estimated by multivariable logistic regression. RESULTS: In total, 2314 cases were included in the analysis (unvaccinated n=923, double-vaccinated n=551, triple-vaccinated n=803, quadruple-vaccinated n=37). SARS-CoV-2 infections occurred after a median of 151 (range 14-347) days in patients being double-vaccinated, and after 88 (range 14-270) days in those with a third vaccination. Hospitalisation was required in 15% of unvaccinated, 8% of double-vaccinated and 3% of triple-vaccinated/quadruple-vaccinated patients (p<0.001). Mortality was 2% in unvaccinated, 1.8% in the double-vaccinated and 0.6% in triple-vaccinated patients. Compared with unvaccinated patients, double-vaccinated (OR 0.43, 95% CI 0.29 to 0.62) and triple-vaccinated (OR 0.13, 95% CI 0.08 to 0.21) patients showed a significant lower risk of COVID-19-related hospitalisation. Using multivariable analysis, the third vaccination was significantly associated with a lower risk for COVID-19-related death (OR 0.26; 95% CI 0.01 to 0.73). CONCLUSIONS: Our cross-sectional data of COVID-19 infections in patients with IRD showed a significant reduction of hospitalisation due to infection in double-vaccinated or triple-vaccinated patients compared with those without vaccination and even a significant reduction of COVID-19-related deaths in triple-vaccinated patients. These data strongly support the beneficial effect of COVID-19 vaccination in patients with IRD. TRIAL REGISTRATION NUMBER: EuDRACT 2020-001958-21.

The impact of immunomodulating treatment on the immunogenicity of COVID-19 vaccines in patients with immune-mediated inflammatory rheumatic diseases compared to healthy controls. A Swedish nationwide study (COVID19-REUMA).

OBJECTIVES: To elucidate antibody responses after the second and third dose of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs). METHODS: Antibody levels to antigens representing spike full length protein and spike S1 were measured before vaccination, 2-12 weeks after the second dose, before and after the third dose using multiplex bead-based serology assay. Positive antibody response was defined as antibody levels over cut off (seropositivity) in seronegative individuals or ≥ 4-fold increase in antibodies in individuals seropositive for both spike proteins. RESULTS: Patients (n = 414) receiving b/ts DMARDs (283 had arthritis, 75 systemic vasculitis and 56 other autoimmune diseases) and controls (n = 61) from five Swedish regions participated. Treatments groups were: rituximab (n = 145); abatacept (n = 22); Interleukin 6 receptor inhibitors [IL6i (n = 79)]; JAnus Kinase Inhibitors [JAKi (n = 58)], Tumour Necrosis Factor inhibitor [TNFi (n = 68)] and Interleukin12/23/17 inhibitors [IL12/23/17i (n = 42)]. Percentage of patients with positive antibody response after two doses was significantly lower in rituximab (33,8%) and abatacept (40,9%) (p < 0,001) but not in IL12/23/17i, TNFi or JAKi groups compared to controls (80,3%). Higher age, rituximab treatment and shorter time between last rituximab course and vaccination predicted impaired antibody response. Antibody levels collected 21-40 weeks after second dose decreased significantly (IL6i: p = 0,02; other groups: p < 0,001) compared to levels at 2-12 week but most participants remained seropositive. Proportion of patients with positive antibody response increased after third dose but was still significantly lower in rituximab (p < 0,001). CONCLUSIONS: Older individuals and patients on maintenance rituximab have an impaired response after two doses of COVID-19 vaccine which improves if the time between last rituximab course and vaccination extends and also after an additional vaccine dose. Rituximab patients should be prioritized for booster vaccine doses. TNFi, JAKi and IL12/23/17i does not diminished humoral response to primary and an additional vaccination.

Correlates of breakthrough Omicron (B.1.1.529) infections in a prospective cohort of vaccinated patients with rheumatic diseases.

BACKGROUND: Data on the effectiveness of SARS-CoV-2 vaccines and the durability of protection against the prevalent Omicron variant are scarce, especially in patients with autoimmune rheumatic diseases (AIRDs). Hence, we prospectively studied Omicron breakthrough infections in patients with AIRDs and attempted to isolate associated risk factors. METHODS: Patients with AIRDs who had completed primary vaccination with either AZD1222 or BBV152 vaccines were included and prospectively followed up from January 2022 onwards for the development of breakthrough Omicron infections. The time interval from the last event [2nd dose of vaccination (V) or past COVID-19 infection (I) whichever was later] to Omicron infection was recorded. Patients were divided based on the events and their order of occurrence into V + V, V + I, I + V, V + I + V, and V + V + I groups. The incidence of breakthrough infections and their predictors were studied with a focus on the vaccine type and hybrid (H) immunity (vaccinated individuals with a history of COVID-19 infection). RESULTS: We included 907 patients with AIRDs (53.5 ± 11.7 years and a male-to-female ratio of 1:5.1), and the majority of patients had received AZD1222 (755, 83.2%). Breakthrough infections were observed in 158 of 907(17.4%) of which 97 (10.4%) were confirmed by RT-PCR. Breakthrough infections were significantly greater in the V versus the H group (15.7% and 3.5%, log-rank test, p = < 0.01). Among the hybrid group, the order of infection and vaccination had no bearing on the risk of breakthrough infections. On multivariate analysis, breakthrough infections were significantly lesser in the H versus the V group [HR: 0.2(0.1-0.4); p = 0.01]. CONCLUSION: The risk of breakthrough Omicron infections in fully vaccinated patients with AIRDs was 17.4% with a significantly lower risk in patients with hybrid immunity.

Immunology of pregnancy and reproductive health in autoimmune rheumatic diseases. Update from the 11th International Conference on Reproduction, Pregnancy and Rheumatic Diseases.

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as "unmet needs", such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.

Telerheumatology: before, during, and after a global pandemic.

PURPOSE OF REVIEW: In early 2020, the COVID-19 global pandemic shifted most healthcare to remote delivery methods to protect patients, clinicians, and hospital staff. Such remote care delivery methods include the use of telehealth technologies including clinical video telehealth or telephone visits. Prior to this, research on the acceptability, feasibility, and efficacy of telehealth applied to rheumatology, or telerheumatology, has been limited. RECENT FINDINGS: Telerheumatology visits were found to be noninferior to in-person visits and are often more time and cost effective for patients. Clinicians and patients both noted the lack of a physical exam in telehealth visits and patients missed the opportunity to have lab work done or other diagnostic tests they are afforded with in-person visits. Overall, patients and clinicians had positive attitudes toward the use of telerheumatology and agreed on its usefulness, even beyond the pandemic. SUMMARY: Although telerheumatology has the potential to expand the reach of rheumatology practice, some of the most vulnerable patients still lack the most basic resources required for a telehealth visit. As the literature on telerheumatology continues to expand, attention should be paid to health equity, the digital divide, as well as patient preferences in order to foster true shared decision-making over telehealth.

SARS-CoV-2 infection in patients with systemic autoimmune diseases.

Systemic autoimmune diseases (SAD) are a heterogeneous group of diseases with a common aetiopathogenic basis affecting all ages characterised by a systemic phenotypic expression with a wide range of severity and outcomes that often require immunosuppressive therapies, leaving patients at high risk of infection. Knowledge of the impact of COVID-19 in patients with SAD is limited because most are included in studies carried out in patients with autoimmune and rheumatic diseases (mainly inflammatory arthritis). Most studies supported an increased risk of SARS-Cov-2 infection in patients with AD and SAD. Although case-control studies reported no significant differences in the rate of poor outcomes between patients with and without AD, large population-based studies analysing baseline risk factors reported a 2-3 times higher rate of poor outcomes in patients with AD, especially in those with SAD. Individual risk factors associated with poor outcomes included gender male, older age, and underlying comorbidities and therapies (glucocorticoids, sulfasalazine, immunosuppressants and rituximab). Patients with SAD had less favourable COVID-19 outcomes than those with inflammatory arthritis, possibly due to a differentiated underlying therapeutic approach (glucocorticoids, immunosuppressants and B-cell depleting agents for most SAD, anti-cytokine therapies and JAK inhibitors for inflammatory arthritis). Despite the limited evidence, most studies suggest that patients with SAD have an increased risk of a worse evolution of SARS-CoV-2 infection, including a greater risk of hospitalisation/ICU admission and worse survival rates and, therefore, should be considered a high-risk group for COVID-19.

Long COVID in autoimmune rheumatic diseases.

Consequences of Corona Virus Disease-19 (COVID-19) in patients with rheumatic diseases (RDs) are clinically diverse. SARS-CoV-2 infection has been associated with various autoimmune and rheumatic manifestations over the past three years. Emerging evidence points to the possibility of Long COVID predisposition in rheumatic patients due to the changes in immune regulatory response. The aim of this article was to overview data on the pathobiology of Long COVID in patients with RDs. Related risk factors, clinical characteristics, and prognosis of Long COVID in RDs were analyzed. Relevant articles were retrieved from Medline/PubMed, Scopus, and Directory of Open Access Journals (DOAJ). Diverse mechanisms of viral persistence, chronic low-grade inflammation, lasting production of autoantibodies, endotheliopathy, vascular complications, and permanent tissue damage have been described in association with Long COVID. Patients with RDs who survive COVID-19 often experience severe complications due to the immune disbalance resulting in multiple organ damage. Regular monitoring and treatment are warranted in view of the accumulating evidence.

Case Report: Acquired Brown Syndrome after COVID-19 Vaccination.

SIGNIFICANCE: Brown syndrome, or superior oblique tendon sheath syndrome, is characterized by limitation of elevation on adduction. The disorder is thought to involve the trochlea/superior oblique tendon complex through traumatic, surgical, and inflammatory mechanisms. It could be an indication of multiple underlying immunological or rheumatological disorders. PURPOSE: This study aimed to report an unusual strabismus after receiving the first dose of a live attenuated coronavirus disease 2019 (COVID-19) vaccine. CASE REPORT: A 31-year-old female patient presented with painful vertical diplopia and tenderness of the left trochlear area 3 days after the first dose of COVID-19 vaccination. She had a compensatory chin elevation and face turn to the right, as well as a left 10-prism-diopter hypotropia in the primary position, which increased to 15 prism diopters in the right gaze and disappeared in the left gaze. Ocular motility revealed the limitation of elevation on adduction. The patient denied any history of ocular trauma and was consequently investigated for dysthyroid disease and various immunological and rheumatological disorders, which were excluded. A Hess chart was obtained to document the motility disorder. CONCLUSIONS: We report a case of acquired Brown syndrome in a 31-year-old otherwise healthy woman shortly after COVID-19 vaccination. It is possible that the patient may have developed trochleitis and/or superior oblique tenosynovitis brought on by cross-reacting antibodies generated by the immune response to the vaccine. In the age of the widest vaccination campaign in human history, it is highly likely that we will continue to observe many unexpected potential adverse effects of these vaccines in our clinical practice.

Physical Activity: A Strategy to Improve Antibody Response to a SARS-CoV-2 Vaccine Booster Dose in Patients With Autoimmune Rheumatic Diseases.

BACKGROUND: Physical activity associates with improved immunogenicity following a 2-dose schedule of CoronaVac (Sinovac's inactivated SARS-CoV-2 vaccine) in patients with autoimmune rheumatic diseases (ARD). This study evaluates whether physical activity impacts vaccine-induced antibody responses to a booster dose in this population. METHODS: This was a phase-4 trial conducted in São Paulo, Brazil. Patients with ARD underwent a 3-dose schedule of CoronaVac. One month after the booster, we assessed seroconversion rates of anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity. Physical activity was assessed through questionnaire. RESULTS: Physically active (n = 362) and inactive (n = 278) patients were comparable for most characteristics; however, physically active patients were younger (P < .01) and had a lower frequency of chronic inflammatory arthritis (P < .01). Adjusted models showed that physically active patients had ∼2 times odds of seroconversion rates (OR: 2.09; 95% confidence interval, 1.22 to 3.61), ∼22% greater geometric mean titers of anti-S1/S2 IgG (22.09%; 95% confidence interval, 3.91 to 65.60), and ∼7% greater neutralizing activity (6.76%; 95% confidence interval, 2.80 to 10.72) than inactive patients. CONCLUSIONS: Patients with ARD who are physically active have greater odds of experiencing better immunogenicity to a booster dose of CoronaVac. These results support the recommendation of physical activity to improve vaccination responses, particularly for immunocompromised individuals.

Genetic predisposition between coronavirus disease 2019 and rheumatic diseases: A 2-sample Mendelian randomization study.

OBJECTIVE: The causalities between the coronavirus disease 2019 (COVID-19) and the risk of rheumatic diseases remain unclear. The purpose of this study was to investigate the causal effect of COVID-19 on rheumatic disease occurrence. METHODS: Single nucleotide polymorphisms (SNPs), acquired from published genome-wide association studies, were used to perform 2-sample Mendelian randomization (MR) on cases diagnosed with COVID-19 (n = 13 464), rheumatic diseases (n = 444 199), juvenile idiopathic arthritis (JIA, n = 15 872), gout (n = 69  374), systemic lupus erythematosus (SLE, n = 3094), ankylosing spondylitis (n = 75 130), primary biliary cholangitis (PBC, n = 11 375) and primary Sjögren's syndrome (n = 95 046). Three MR methods were used in the analysis based on different heterogeneity and pleiotropy using the Bonferroni correction. RESULTS: The results revealed a causality between COVID-19 and rheumatic diseases with an odds ratio (OR) of 1.010 (95% confidence interval [CI], 1.006-1.013; P = .014). In addition, we observed that COVID-19 was causally associated with an increased risk of JIA (OR 1.517; 95%CI, 1.144-2.011; P = .004), PBC (OR 1.370; 95%CI, 1.149-1.635; P = .005), but a decreased risk of SLE (OR 0.732; 95%CI, 0.590-0.908; P = .004). Using MR, 8 SNPs were identified to associate with COVID-19 and recognized as significant variables. None of them were previously reported in any other diseases. CONCLUSIONS: This is the first study to use MR to explore the impact of COVID-19 on rheumatic diseases. From a genetic perspective, we found that COVID-19 could increase the risk of rheumatic diseases, such as PBC and JIA, but decrease that of SLE, thereby suggesting a potential surge in the disease burden of PBC and JIA following the COVID-19 pandemic.

Facilitators and barriers of vaccine uptake in patients with autoimune inflammatory rheumatic disease: a scoping review.

OBJECTIVES: Patients with autoimmune inflammatory rheumatic diseases (AIRD) often have lower vaccination coverage rates compared with the general population, despite being disproportionately affected by infectious complications. We aim to systematically review the literature regarding vaccination willingness and hesitancy in AIRD. METHODS: A scoping review was conducted in PubMed, EMBASE and the Cochrane Library in June 2021. Study selection was performed by two independent reviewers and data were extracted using a standardised form. Risk of bias was assessed using instruments from McMaster University. Identified barriers were categorised into the WHO's measuring behavioural and social drivers (BeSD) of vaccination conceptual model. RESULTS: The search yielded 1644 hits of which 30 publications were included (cross-sectional studies based on interviews (n=27) and intervention studies (n=3)). The majority of studies reported barriers to influenza and pneumococcal vaccination only (n=9) or in combination with another vaccination (n=8) from the patients' perspective. Only one study assessed the view of rheumatologists. Coverage of domains matched to the BeSD model suggests a lack of awareness of infection risk by both patients and physicians. Patients mainly mentioned behavioural and social factors that negatively influenced their willingness to be vaccinated while physicians mentioned organisational deficits as major barriers. CONCLUSIONS: The view on vaccination in patients with AIRD diverges between patients and rheumatologists. Our results show that in-depth counselling on vaccines is important for patients, whereas physicians need support in implementing specific immunisation recommendations. The themes identified provide a starting point for future interventions to improve vaccine rates in patients with AIRD.

Systemic sclerosis and COVID-19 vaccine safety: short-term insights from the global COVID-19 vaccination in autoimmune disease (COVAD) survey.

The safety profile of COVID-19 vaccines is understudied in patients with systemic sclerosis (SSc). We compared short-term adverse events (AEs) 7 days following vaccination in patients with SSc vs other rheumatic (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). The COVID-19 Vaccination in autoimmune diseases (COVAD) self-reporting e-survey was circulated by a group of > 110 collaborators in 94 countries from March to December 2021. AEs were analyzed between different groups using regression models. Of 10,679 complete respondents [73.8% females, mean age 43 years, 53% Caucasians], 478 had SSc. 83% had completed two vaccine doses, Pfizer-BioNTech (BNT162b2) (51%) was the most common. Minor and major AEs were reported by 81.2% and 3.3% SSc patients, respectively, and did not differ significantly with disease activity or different vaccine types, though with minor symptom differences. Frequencies of AEs were not affected by background immunosuppression, though SSc patients receiving hydroxychloroquine experienced fatigue less commonly (OR 0.4; 95% CI 0.2-0.8). Frequency of AEs and hospitalisations were similar to other AIRDs, nrAIDs, and HC except a higher risk of chills (OR 1.3; 95% CI 1.0-1.7) and fatigue (OR 1.3; 95% CI 1.0-1.6) compared to other AIRDs. COVID-19 vaccines were largely safe and well tolerated in SSc patients in the short term. Background immunosuppression and disease activity did not influence the vaccination-related short-term AEs.