Autoimmune Disease Patients Research Articles

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

BackgroundData 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.MethodsRetrospective 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.ResultsARD 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.ConclusionWe 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).

Infectious risk when prescribing rituximab in patients with hypogammaglobulinemia acquired in the setting of autoimmune diseases

We conducted a single-centre retrospective cohort study in a French University Hospital between 2010 and 2018 to describe the risk of severe infectious event (SIE) within 2 years after the date of first rituximab infusion (T0) prescribed after the evidence of acquired hypogammaglobulinemia (gamma globulins [GG] ≤ 6 g/L) in the setting of autoimmune diseases (AID) other than rheumatoid arthritis. SIE occurred in 26 out of 121 included patients. Two years cumulative incidence rates were 12.7 % (95 % CI 5.1–23.9) in the multiple sclerosis/neuromyelitis optica spectrum disorder group (n = 48), 27.6 % (95 % CI 15.7–40.9) in the ANCA-associated vasculitis group (n = 48) and 30.6 % (95 % CI 13.1–50.3) in the ‘other AID’ group (n = 25). Median GG level at T0 was 5.3 g/l (IQR 4.1–5.6) in the 'SIE' group and 5.6 g/l (IQR 4.7–5.8) in the 'no SIE' group (p = 0.04).In regression analysis, risk of SIE increased with Charlson comorbidity index ≥ 3 (OR 2.77; 95 % CI 1.01–7.57), lung disease (OR 3.20; 95 % CI 1.27–7.99), GG < 4 g/L (OR 3.39; 95 % CI 1.02–11.19), concomitant corticosteroid therapy (OR 4.13; 95 % CI 1.63–10.44), previous cyclophosphamide exposure (OR 2.69; 95 % CI 1.10–6.61), a lymphocyte count < 1000 cells/µL (OR 2.86; 95 % CI 1.12–7.21) and absence of pneumococcal vaccination (OR 3.50; 95 % CI 1.41–8.70).These results may help to inform clinical decision when considering a treatment by rituximab in immunosuppressed AID patients with hypogammaglobulinemia.

Evaluation of left ventricular function of pregnant women with autoimmune diseases using speckle tracking echocardiography.

Pregnancy can cause fluctuations in autoimmune diseases (AD) women, which may aggravate the cardiac damage. Maternal heart function is very important for maternal and fetal health. Therefore, early and accurate evaluation of the heart function of AD pregnant women is necessary. This study was aimed to evaluate the left ventricular (LV) function of AD pregnant women using two-dimensional speckle tracking echocardiography (2DSTE). A total of 96 subjects, including 26 non-pregnant AD patients (AD group), 33 AD pregnant women (AD-P group), and 37 healthy pregnant women (H-P group) were conducted. Baseline clinical and conventional echocardiography characteristics of all the subjects were collected. The 2DSTE was performed to acquire layer-specific strain parameters of LV. Compared with H-P group, AD-P group showed no significant differences in GLSmid and GLSepi. However, the GLSendo (24.10 [22.30 to 25.40] vs. 21.70 [19.05 to 25.15], P = 0.023) and ΔGLS (5.50 [4.80 to 6.00] vs. 4.90 [4.20 to 5.80], P = 0.017) were decreased, while the PSD (27 [23 to 32] vs. 32 [24 to 44], P = 0.014) was increased. At the segmental level, there was no significant difference in apex LSmid and LSepi between the two groups, while the AD-P group showed transmural dysfunction in basal and middle segments, and the LSendo in apex segments (32.84 [28.34 to 34.25] vs. 27.97 [21.87 to 33.61], P = 0.021) were significantly decreased. Compared with AD group, AD-P group showed no significant difference in ΔGLS, PSD, and GLS parameters of three layers. For the segmental level, there were no significant differences in the LSepi of the apex segment and the LS in three layers of the basal and middle segments between the two groups, while LSendo (32.69 [29.13 to 35.53] vs. 27.97 [21.87 to 33.60], P = 0.017) and LSmid (24.70 [22.24 to 27.78] vs. 21.32 [16.91 to 26.11], P = 0.023) in apex segments were significantly lower in AD-P group. The anti-SSA/Ro antibody were positive independently correlated with PSD. In conclusion, layer-specific strain parameters and PSD by 2DSTE provide an accurate and reproducible measurement of myocardial function. There are subclinical LV myocardial dysfunction in AD pregnant women. Besides, the positive of anti-SSA/Ro antibody maybe associated with LV myocardial dysfunction.

Catheter ablation of atrial fibrillation in patients with autoimmune disease: A propensity score matching study based on the China Atrial Fibrillation Registry.

Evidence on outcomes of catheter ablation (CA) for atrial fibrillation (AF) in patients with autoimmune disease (AD) is limited. Patients with AD had worse outcomes after CA procedures for AF. A retrospective analysis was performed in patients undergoing AF ablation between 2012 and 2021. The risk of recurrence after ablation was investigated in patients with AD and a 1:4 propensity score matched non-AD group. We identified 107 patients with AD (64 ± 10 years, female 48.6%) who were matched with 428 non-AD patients (65 ± 10 years, female 43.9%). Patients with AD exhibited more severe AF-related symptoms. During the index procedure, a higher proportion of AD patients received nonpulmonary vein trigger ablation (18.7% vs. 8.4%, p = 0.002). Over a median follow-up of 36.3 months, patients with AD experienced a similar risk of recurrence with the non-AD group (41.1% vs. 36.2%, p = 0.21, hazard ratio [HR]: 1.23, 95% confidence interval [CI]: 0.86-1.76) despite a higher incidence of early recurrences (36.4% vs. 13.5%, p = 0.001). Compared with non-AD patients, patients with connective tissue disease were at an increased risk of recurrence (46.3% vs. 36.2%, p = 0.049, HR: 1.43, 95% CI: 1.00-2.05). Multivariate Cox regression analysis showed that the duration of AF history and corticosteroid therapy were independent predictors of postablation recurrence in patients with AD. In patients with AD, the risk of recurrence after ablation for AF during the follow-up was comparable with non-AD patients, but a higher risk of early recurrence was observed. Further research into the impact of AD on AF treatment is warranted.

Acute Outcomes of Cardiac Operations in Patients With Autoimmune Disorders: A National Analysis.

Accelerated atherosclerosis, inflammation, and valve pathology are known complications of autoimmune connective tissue diseases (AID). However, outcomes of coronary artery bypass graft surgery (CABG) or valve operations among these patients remain underexamined. All adult hospitalizations for elective CABG or valve procedures were identified from the 2010-2019 Nationwide Readmissions Database. Autoimmune connective tissue disease was defined to include systemic lupus erythematosus (SLE), antiphospholipid syndrome (APLS), polymyalgia rheumatica (PMR), and other autoimmune AIDs. Entropy balancing was applied to generate balanced patient cohorts. Multivariable regression models were constructed to assess the independent associations between AID and outcomes of interest. Of ∼1 652 573 patients, 21 019 (1.3%) had AID (23.7% SLE, 17.2% APLS, 29.5% PMR, and 29.6% other). Autoimmune connective tissue disease patients were more frequently female (60.8 vs 33.1%, P < .001) and insured by Medicare (71.4 vs 62.2%, P < .001) and presented with a higher comorbidity index (5.2 ± 1.8 vs 4.1 ± 1.8, P < .001). Further, AID less frequently underwent isolated CABG (39.0 vs 52.3%) but more commonly isolated valve operations (41.9% vs 31.0%, P < .001), relative to non-AID. Following risk-adjustment, AID was not linked with increased odds of mortality or cardiac complications. However, AID was linked with a greater risk of thrombotic complications, blood transfusion, and non-elective readmission within 30days, as well as a +$900 decrement in hospitalization costs. Autoimmune connective tissue disease patients demonstrated acceptable outcomes following CABG and valve procedures. However, novel prophylactic care pathways should be developed and instituted to address greater thrombotic and blood transfusion risk. Further investigation is needed to identify factors contributing to greater non-elective readmissions among these patients.

Research progress on the relationship between COVID-19 and autoimmune diseases

Different autoantibodies can be detected in patients with coronavirus disease 2019 (COVID-19). It is reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could induce autoimmune diseases (AID), including children's multisystem inflammatory syndrome (MIS-C), Guillain Barre syndrome (GBS), Autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP) and thyroid autoimmune diseases. This article mainly reviews the similarities between COVID-19 and AID, the possibility of COVID-19 inducing AID, the risk of AID patients infected or vaccinated against COVID-19. The purpose is to provide strategies for the prevention, management and treatment of AID during the epidemic.

Outcome of COVID-19 in patients with autoimmune bullous diseases.

Background Data on outcomes of Coronavirus disease 2019 (COVID-19) infection in autoimmune bullous diseases (AIBDs) patients is scarce. Materials and methods This single-centre survey-based-observational study included patients registered in the AIBD clinic of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. All registered patients were contacted over telephone between June and October 2021. A survey was conducted after obtaining informed consent. Results Among 1389 registered patients, 409 completed the survey. Two hundred and twenty-two (55.3%) patients were females and 187 (45.7%) were males. The mean age was 48.52 ± 14.98 years. Active disease was reported by 34% patients. The frequency of COVID-19 infection in responders was 12.2% (50/409), with a case-fatality ratio of 18% (9/50). Rituximab infusion after the onset of pandemic significantly increased the risk of COVID-19 infection. Active AIBD and concomitant comorbidities were significantly associated with COVID-19 related death. Limitation Relative risk of COVID-19 infection and complications among AIBD patients could not be estimated due to lack of control group. The incidence of COVID-19 in AIBD could not be determined due to lack of denominator (source population) data. Other limitations include telephonic nature of the survey and lack of COVID-19 strain identification. Conclusion Use of rituximab is associated with higher probability of COVID-19 infection, while advanced age, active disease and presence of comorbidities may increase the risk of COVID-19 mortality in AIBD patients.

Prevalence of autoimmune diseases in patients with type 1 diabetes

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Essential role of IL-17A in activating Treg cells in autoimmune uveitis

Abstract The balance between Th17 cells and regulatory T (Treg) cells is critical for host homeostasis. The signature cytokine of Th17 cells, IL-17A, is a pro-inflammatory cytokine associated with various autoimmune diseases in patients and in animal models. Our previous study demonstrated that IL-17A limits pathogenicity of Th17 cells by inducing IL-24. In this study, we investigate the role of IL-17A in regulating Treg cells. In-vitro studies showed that IL-17A promotes both the differentiation and suppressive functions of Treg cells. Adoptive transfer of IL-17A-treated Treg cells is more potent to ameliorate experimental autoimmune uveitis (EAU) in mice when compared to the control Treg cells. We found that the induction of Treg cells is impaired in Il17ra −/−mice after EAU immunization and Il17ra −/−naïve T cells are less effective in their differentiation into Treg cells in EAU compared to wild-type cells. Mechanistic studies revealed that IL-17A activates NF-kB signaling and inhibits TAZ, a Foxp3 suppressor, during Treg cell differentiation. In conclusion, our data suggest that IL-17A is involved in Tregs induction and/or maintenance, and that this has a role in controlling the autoimmune response. Natural Science Foundation of Guangdong Province (2019A1515010956, 2021A1515010569, 2022A1515012450) Fundamental Research Fund of the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center.

Seroprevalence of SARS-CoV-2 in treatment naïve patients of rheumatological diseases

Dear Sir,COVID-19 is of paramount concern in the rheumatology community. As per current consensus, patients of rheumatological diseases (RDs) are at higher risk of SARS-CoV-2 infection than the general population (high agreement but very low grade of evidence); however, contradictory reports are available regarding its seroprevalence and association with severity and mortality. However, these inferences are mainly based on patients who have long-standing RDs and on various therapies. Then what would happen to those who are treatment-naive, mildly symptomatic, or carrying this disease unknowingly in the community during this pandemic? To explore this aspect, we screened blood samples of clinically suspected patients of autoimmune diseases (ADs) for COVID-19 IgG antibody during the pandemic in the pre-vaccination period. Based on clinical profile, antinuclear antibody (ANA), antineutrophilic cytoplasmic antibody (ANCA), and myositis-associated autoantibodies were tested. Out of 268 clinically suspected cases of RDs, 131 samples were positive for autoantibodies: RD group (114 ANA+08 myositis associated antibody+09 ANCA), and the rest 137 were negative (non-RD group). Out of these, three samples each from RD (3/131; 2.29%) and non-RD group (3/137; 2.17%) turned out to be positive for COVID-19 IgG antibody (EUROIMMUN, Germany), suggesting no increased prevalence of COVID19 in patients of the RD group (OR=1.046, 95% CI: 0.145–7.53, P=0.9645). Among the RD group, two patients were finally diagnosed with systemic lupus erythematosus (SLE); however, others did not turn up again to the hospital to comment on the final diagnosis. None of these COVID-19 positive patients had any known comorbidities or RD-related treatment. These positive patients from both groups had almost similar mildto-moderate COVID-19 disease courses with a favorable outcome. A meta-analysis found a marginal association of ADs with increased risk of severity and mortality of COVID-19 disease (Risk of severity: OR=1.21, 95% CI: 0.58–2.5, P=0.79; Risk of mortality: OR=1.31, 95% CI: 0.33–5.2, P=0.95); however, the difference was not significant. Studies have documented COVID-19 frequency of 2.4% (4/165) among SLE patients with severe cases mostly in coexisting comorbidities. Even recent consensus has suggested older age, presence of comorbidities, and use of prednisolone ≥10 as a risk factor for poor outcome in these two coexisting diseases. Unlike the previous reports, the present study highlighted the susceptibility of treatment naïve cases of RDs for COVID-19. The RD group either has an almost similar SARS-CoV-2 prevalence as the non-RD group (2.29% vs. 2.17%) or even lowers than the general population (2.29% vs. 7%). In conclusion, RD itself does not seem to be a risk factor for SARS-CoV2 infection, even in treatment naïve patients; however, disease outcome may depend on various coexisting factors/comorbidities. Inter-talk between SARS-CoV-2 and RDs yet to be explored.

Immunosuppressive therapy management in cancer patients with autoimmune diseases treated with immune checkpoint inhibitors: A case series and systematic literature review.

Prescribing immune checkpoint inhibitors (ICIs) to cancer patients with an autoimmune disease (AID) is presumed safe when cautious adverse event management is applied. However, guidelines on immunosuppressant (IS) adaptations are limited and real-world evidence is scarce. Current practice of IS adaptations is described in a case series of AID patients treated with ICIs in a tertiary university hospital in Belgium (1/1/2016-31/12/2021). Patient, drug and disease-related data were documented using retrospective chart review. A systematic search of the PubMed database was performed to identify similar cases (1/1/2010-30/11/2022). Sixteen patients were described in the case series (62% with active AID). Systemic IS were changed before ICI initiation in 5/9 patients. Four patients continued therapy, of which one achieved partial remission. Patients who had IS (partially) stopped before ICI start (n = 4) had AID flares in two cases; immune-related adverse events in three cases. In the systematic review, 37 cases were identified in 9 articles. Corticosteroids (n = 12) and non-selective IS (n = 27) were continued in, respectively, 66% and 68% of patients. Methotrexate was frequently discontinued (13/21). Biologicals, excluding tocilizumab and vedolizumab, were withheld during ICI treatment. Out of all patients with flares (n = 15), 47% had stopped IS therapy before ICI start and 53% had continued their AID drugs. A detailed overview of IS management in patients with AID receiving ICI therapy is presented. Expanding the knowledge base germane to IS management with ICI therapy in the diverse population is essential to evaluate their mutual impact, thus advancing responsible patient care.

Living-Donor Liver Transplant and Improved Post-Transplant Survival in Patients with Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is the leading indication of liver transplantation (LT) among autoimmune liver disease patients. There is a scarcity of studies comparing survival outcomes between living-donor liver transplants (LDLT)s and deceased-donor liver transplants (DDLTs) in this population. Using the United Network for Organ Sharing database, we compared 4679 DDLTs and 805 LDLTs. Our outcome of interest was post-LT patient survival and post-LT graft survival. A stepwise multivariate analysis was performed, adjusting for recipient age, gender, diabetes mellitus, ascites, hepatic encephalopathy, cholangiocarcinoma, hepatocellular carcinoma, race, and the model for end-stage liver disease (MELD) score; donor' age and sex were also included to the analysis. According to univariate and multivariate analysis, LDLT had a patient and graft survival benefit compared to DDLT (HR, 0.77, 95% CI 0.65-0.92; p < 0.002). LDLT patient survival (95.2%, 92.6%, 90.1%, and 81.9%) and graft survival (94.1%, 91.1%, 88.5%, and 80.5%) at 1, 3, 5, and 10 years were significantly better than DDLT patient survival (93.2%, 87.6%, 83.3%, and 72.7%) and graft survival (92.1%, 86.5%, 82.1%, and 70.9%) (p < 0.001) in the same interval. Variables including donor and recipient age, male recipient gender, MELD score, diabetes mellitus, hepatocellular carcinoma, and cholangiocarcinoma were associated with mortality and graft failure in PSC patients. Interestingly, Asians were more protected than Whites (HR, 0.61; 95% CI, 0.35-0.99; p < 0.047), and cholangiocarcinoma was associated with the highest hazard of mortality (HR, 2.07; 95% CI, 1.71-2.50; p < 0.001) in multivariate analysis. LDLT in PSC patients were associated with greater post-transplant patient and graft survival compared to DDLT patients.

Medical complications following adult spinal deformity correction in patients with autoimmune disease.

An aberrant inflammatory response, which plays a role in the development of postoperative complications, is observed in autoimmune diseases, Yet, there is a paucity of literature regarding the effects of autoimmune diseases after adult spinal deformity (ASD) surgery. The goal of this study was to determine the effects of autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus) on postoperative medical complications, patient-reported outcome measures (PROMs), and radiographic alignment in patients who underwent ASD surgery. Propensity-score matching for age and sex was performed for patients with autoimmune disease (group A) and nonautoimmune patients (group NA1). Postoperative medical complications, preoperative and 2-year follow-up PROMs, and preoperative, immediate postoperative, and 2-year follow-up radiographic alignment were evaluated. Among 386 patients (27 in group A and 359 in group NA1), autoimmune patients had a higher incidence of respiratory complications (11.1% vs 2.2%, p = 0.036), gastrointestinal complications (14.8% vs 3.1%, p = 0.016), urinary tract infections (14.8% vs 3.1%, p = 0.016), cholecystitis (7.4% vs 0%, p = 0.005), and fever of unknown origin (14.8% vs 0%, p < 0.001). Autoimmune patients had worse preoperative ODI (54.2 vs 44.7, p = 0.004) and 2-year follow-up Scoliosis Research Society 22-item Questionnaire (SRS-22) scores (3.1 vs 3.5, p = 0.039), with higher preoperative sacral slope (23.4° vs 17.8°, p = 0.020). Propensity-score matching for age and sex yielded 27 pairs (group A and group NA2). Having at least one medical complication (group A 74.1% vs group NA2 22.2%, p < 0.001), total complications per person (1.3 vs 0.3, p = 0.010), prognostic nutrition index (44.8 vs 48.6, p = 0.034), steroid use (51.9% vs 0%, p < 0.001), immunosuppressant use (48.1% vs 0%, p < 0.001), length of hospital stay (38 vs 27 days, p = 0.018), and discharge to care facility (29.6% vs 7.4%, p = 0.036) were higher in group A. Preoperative ODI (54.2 vs 43.2, p = 0.011) and 2-year follow-up SRS-22 scores (3.1 vs 3.6 p = 0.019) were worse in group A. No differences were observed in radiographic alignment. Patients with autoimmune disease had higher complication rates and worse PROMs following ASD surgery in this study. There was no difference in spinal alignment compared with controls. Multidisciplinary planning and full disclosure of possible adverse effects should be completed prior to correction of ASD in patients with autoimmune disease.

Vitamin D Deficiency as a Potential Inducer of Autoimmune Diseases in Patients with Xeroderma Pigmentosum

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Economic Evaluation of Evusheld for Preexposure Prevention of COVID-19 in High-Risk Populations: Early Evidence from Thailand.

The introduction of Coronavirus disease 2019 (COVID-19) vaccines urged all Thais to seek prevention of serious illness and death from COVID-19. However, immunocompromised individuals might not be able to achieve an efficient immune response from these vaccines. This study aimed to evaluate the cost-effectiveness and budget impact of introducing Evusheld (tixagevimab plus cilgavimab) for three patient groups-organ transplant, autoimmune disease, and dialysis patients, from the Thai government perspective. A Markov decision model was developed to compare the use of Evusheld plus COVID-19 vaccines versus COVID-19 vaccines alone. The methodology followed the National HTA Guidelines of Thailand. Model input parameters were collected locally from retrospective data and from a literature review. Evusheld helped prevent COVID-19 infection, severe infection, and death in all three patient groups. Using the Thai threshold of 160,000 Thai Baht (THB) per quality-adjusted life year (QALY) gained, the only scenario found to be cost-effective was that of dialysis patients with inadequate immune response, with an incremental cost-effectiveness ratio (ICER) of 54,700 THB per QALY gained. To make a policy of Evusheld provision cost-effective in other groups, the price of Evusheld had to be lower (a reduction of 44-88% of its current price). The results of one-way sensitivity analysis indicated that the cost-effectiveness of Evusheld was sensitive to changes in the rate of infection, cost and efficacy of Evusheld, proportion of inadequate immune responses, and the probability of moving from a 'recovered' to 'susceptible' status. Among three COVID-19-vaccinated immunocompromised patient populations, this study concluded that Evusheld was cost-effective for dialysis patients with inadequate immune response to the COVID-19 vaccine.

A deep look into the storm: Israeli multi-center experience of coronavirus disease 2019 (COVID-19) in patients with autoimmune inflammatory rheumatic diseases before and after vaccinations.

We aimed to characterize the course of COVID-19 in autoimmune inflammatory rheumatic disease (AIIRD) patients in Israel, taking into consideration several remarkable aspects, including the outcomes of the different outbreaks, the effect of vaccination campaigns, and AIIRD activity post-recovery. We established a national registry of AIIRD patients diagnosed with COVID-19, including demographic data, AIIRD diagnosis, duration and systemic involvement, comorbidities, date of COVID-19 diagnosis, clinical course, and dates of vaccinations. COVID-19 was diagnosed by a positive SARS-CoV-2 polymerase chain reaction. Israel experienced 4 outbreaks of COVID-19 until 30.11.2021. The first three outbreaks (1.3.2020 - 30.4.2021) comprised 298 AIIRD patients. 64.9% had a mild disease and 24.2% had a severe course; 161 (53.3%) patients were hospitalized, 27 (8.9%) died. The 4th outbreak (delta variant), starting 6 months after the beginning of the vaccination campaign comprised 110 patients. Despite similar demographic and clinical characteristics, a smaller proportion of AIIRD patients had negative outcomes as compared to the first 3 outbreaks, with regards to severity (16 patients,14.5%), hospitalization (29 patients, 26.4%) and death (7 patients, 6.4%). COVID-19 did not seem to influence the AIIRD activity 1-3 months post-recovery. COVID-19 is more severe and has an increased mortality in active AIIRD patients with systemic involvement, older age and comorbidities. Vaccination with 3 doses of the mRNA vaccine against SARS-CoV-2 protected from severe COVID-19, hospitalization and death during the 4th outbreak. The pattern of spread of COVID-19 in AIIRD patients was similar to the general population.

Attitudes and factors affecting decision‐making regarding COVID‐19 vaccination among autoimmune rheumatic disease patients

Coronavirus disease-2019 (COVID-19) vaccine hesitancy is a significant threat to the success of COVID-19 vaccination programs. We aimed to assess attitudes and factors affecting the decision-making vis-à-vis COVID-19 vaccination among patients with autoimmune rheumatic diseases (ARDs). A cross-sectional survey of adults with ARDs was conducted between January 2022 and April 2022. All enrolled ARDs patients were asked to answer a questionnaire about their attitudes regarding COVID-19 vaccination. Three hundred patients were included with a female-to-male ratio of 2.5:1. The mean age of the patients was 49.2 ± 15.6 years. Around 37% of patients who hesitated to get the COVID-19 vaccination were apprehensive regarding potential adverse events from the vaccine. About 25% (76 cases) were hesitant about vaccination, of which 15% were uncertain about the vaccine's efficacy, and 15% thought the vaccine was unnecessary because they lived in rural areas where they practiced social distancing. "Family role as a non-working member" was the only factor strongly associated with hesitancy for vaccination (odds ratio of 2.42; 95% CI 1.06-5.57). The attitudes to vaccination showed that the patients were concerned about disease flaring and believed all medicine should be stopped before vaccination. Around one-quarter of ARDs sufferers hesitated to get COVID-19 vaccination. In addition, some patients were disinclined to get vaccinated because they were worried about its efficacy and/or associated adverse events. The findings help healthcare providers plan to counter negative attitudes toward vaccination in ARDs patients to protect them during the COVID-19 era.

Photoacoustic Imaging of COVID-19 Vaccine Site Inflammation of Autoimmune Disease Patients.

Based on the observations made in rheumatology clinics, autoimmune disease (AD) patients on immunosuppressive (IS) medications have variable vaccine site inflammation responses, whose study may help predict the long-term efficacy of the vaccine in this at-risk population. However, the quantitative assessment of the inflammation of the vaccine site is technically challenging. In this study analyzing AD patients on IS medications and normal control subjects, we imaged the inflammation of the vaccine site 24 h after mRNA COVID-19 vaccinations were administered using both the emerging photoacoustic imaging (PAI) method and the established Doppler ultrasound (US) method. A total of 15 subjects were involved, including 6 AD patients on IS and 9 normal control subjects, and the results from the two groups were compared. Compared to the results obtained from the control subjects, the AD patients on IS medications showed statistically significant reductions in vaccine site inflammation, indicating that immunosuppressed AD patients also experience local inflammation after mRNA vaccination but not in as clinically apparent of a manner when compared to non-immunosuppressed non-AD individuals. Both PAI and Doppler US were able to detect mRNA COVID-19 vaccine-induced local inflammation. PAI, based on the optical absorption contrast, shows better sensitivity in assessing and quantifying the spatially distributed inflammation in soft tissues at the vaccine site.

Treatment-resistant depression and risk of autoimmune diseases: evidence from a population-based cohort and nested case-control study

Recent literature indicates that patients with depression had increased immune activation. We hypothesised that treatment-resistant depression (TRD), an indicator of non-responsive depression with long-term dysregulated inflammation, could be an independent risk factor for subsequent autoimmune diseases. We performed a cohort study and a nested case-control study to examine the association between TRD and risk of autoimmune diseases, and to explore potential sex-specific difference. Using electronic medical records in Hong Kong, we identified 24,576 patients with incident depression between 2014 and 2016 without autoimmune history and followed up from diagnosis to death or December 2020 to identify TRD status and autoimmune incidence. TRD was defined as having at least two antidepressant regimens and the third regimen to confirm previous treatment failures. Based on age, sex and year of depression, we matched TRD patients 1:4 to the non-TRD in the cohort analysis using nearest-neighbour matching, and matched cases and controls 1:10 using incidence density sampling in the nested case-control analysis. We conducted survival analyses and conditional logistic regression respectively for risk estimation, adjusting for medical history. Across the study period, 4349 patients without autoimmune history (17.7%) developed TRD. With 71,163 person-years of follow-up, the cumulative incidence of 22 types of autoimmune diseases among the TRD patients was generally higher than the non-TRD (21.5 vs. 14.4 per 10,000 person-years). Cox model suggested a non-significant association (HR:1.48, 95% CI: 0.99–2.24, p = 0.059), whereas conditional logistic model showed a significant association (OR: 1.67, 95% CI: 1.10–2.53, p = 0.017) between TRD status and autoimmune diseases. Subgroup analysis showed that the association was significant in organ-specific diseases but not in systemic diseases. Risk magnitudes were generally higher among men compared to women. In conclusion, our findings provide evidence for an increased risk of autoimmune diseases in patients with TRD. Controlling chronic inflammation in hard-to-treat depression might play a role in preventing subsequent autoimmunity.

OC-01 (Varenicline Solution) Nasal Spray for the Treatment of Dry Eye Disease Signs and Symptoms in Subjects with Autoimmune Disease: Integrated Data from ONSET-1 and ONSET-2.

We evaluate the treatment effect of OC-01 (varenicline solution) nasal spray (VNS) in dry eye disease (DED) subjects from two randomized trials who self-reported autoimmune disease (AID). Post hoc subgroup analysis of subjects reporting a history of AID from the integrated OC-01 VNS 0.03 or 0.06 mg and vehicle control (VC) treatment groups of the ONSET-1 and ONSET-2 trials. Mean change in Schirmer test with anesthesia score (STS, mm) and Eye Dryness Score (EDS) from baseline to 28 days was compared between OC-01 VNS and VC groups. Consistency of treatment effect in subjects with and without AID was evaluated using treatment-subgroup interaction terms in ANCOVA models for mean changes from baseline STS and EDS, and in a logistic regression model for proportion achieving ≥10 mm STS improvement. Of the 891 participants, 31 reported comorbid AID. In all models, the treatment-subgroup interaction terms were not significant (p>0.05), indicating consistency of therapeutic effect of OC-01 VNS in subjects with and without AID. In subjects with AID, the treatment difference for STS was 11.8 mm and -9.3 for EDS and difference for proportion of subjects with ≥10 mm STS improvement was 61.1%. The most common adverse event was sneeze (82-84%), graded as mild by 98% of subjects. OC-01 VNS demonstrated consistency in improving both tear production and patient-reported symptoms in subjects with AID, consistent with pivotal ONSET-1 and 2 trial results. Further investigation is warranted, and results may further support use of OC-01 VNS for DED in AID patients.