Collating the voice of people with autoimmune diseases: Methodology for the Third Phase of the COVAD Studies.

INTRODUCTION: The growing recognition of holistic patient care highlights the various factors shaping the quality of life of individuals with autoimmune and rheumatic diseases (AIRDs). Beyond the traditional disease measures, there is an emerging acknowledgment of the less-explored aspects, including subjective well-being, social determinants of health, comorbidities, mental health, and medication adherence. Moreover, digital health services have empowered patients to engage actively in decision-making alongside clinicians. To explore these domains within the context of AIRDs, the "Collating the Voice of People with Autoimmune Diseases" COVAD survey was conceived, a successor of the previous two COVAD surveys. In this document, we present the study protocol in comprehensive detail. METHODS: The COVAD-3 survey is a cross-sectional patient self-reported e-survey incorporating multiple widely accepted scales/scores to assess various aspects of patients' lifestyles objectively. To ensure the survey's accuracy and usability across diverse regions, it will be translated into multiple languages and subjected to rigorous vetting and pilot testing. It will be distributed by collaborators via online platforms and data will be collected from patients with AIRDs, and healthy individuals over eight months. Data analysis will focus on outcome measures related to various social, demographic, economic, and psychological factors. CONCLUSION: With the increasing awareness to adopt a holistic treatment approach encompassing all avenues of life, the COVAD-3 survey aims to gain valuable insights into the impact of social, demographic, economic, and psychological determinants of health on the subjective well-being in patients with AIRDs, which will contribute to a better understanding of their overall health and well-being.

Impaired health-related quality of life in idiopathic inflammatory myopathies: a cross-sectional analysis from the COVAD-2 e-survey.

Objectives: To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Methods: Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. Results: We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10-15] IIMs vs 13 [11-15] non-IIM AIRDs vs 15 [13-17] nrAIDs vs 17 [15-18] controls, P < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10-15) IIMs vs 15 (13-17) controls, P < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Conclusion: Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs.

Immunogenicity and Loss of Effectiveness of Biologic Therapy for Inflammatory Bowel Disease Patients Due to Anti-Drug Antibody Development.

Many patients with inflammatory bowel disease (IBD) experience a loss of effectiveness to biologic therapy (i.e., anti-TNF therapy, etc.). Therefore, in addition to the adverse effects of the treatment, these patients also face failure to achieve and maintain remission. Immunogenicity, the process of production of antibodies to biological agents, is fundamental to the evolution of loss of response to treatment in IBD patients. The presence of these antibodies in patients is linked to decreased serum drug levels and inhibited biological activity. However, immunogenicity rates exhibit significant variability across inflammatory disease states, immunoassay formats, and time periods. In this review, we aimed to elucidate the immunogenicity and immune mechanisms of antibody formation to biologics, the loss of therapy response, clinical results of biological treatment for IBD from systematic reviews and meta-analyses, as well as to summarize the most recent strategies for overcoming immunogenicity and approaches for managing treatment failure in IBD.

Breakthrough SARS-CoV-2 infection and disease flares in patients with rheumatoid arthritis: result from COVAD e-survey study.

COVID-19 has been suggested as a possible trigger of disease flares in patients with rheumatoid arthritis (RA). However, factors associated with disease flares remain unknown. This study aimed to identify factors associated with breakthrough infection (BIs) and disease flares in patients with RA following COVID-19. We analysed data from RA patients who participated in the COVID-19 vaccination in autoimmune diseases (COVAD) study. Demographic data, patient-reported outcomes, comorbidities, pharmacologic treatment and details regarding disease flares were extracted from the COVAD database. Factors associated with disease flare-ups were determined by multivariate logistic regression analysis. The analysis comprised 1928 patients with RA who participated in the COVAD study. Younger age, Caucasian ethnicity, comorbidities with obstructive chronic pulmonary disease and asthma were associated with COVID-19 breakthrough infection. Moreover, younger age (odds ratio (OR): 0.98, 95% CI 0.96-0.99, p < 0.001), ethnicity other than Asian, past history of tuberculosis (OR: 3.80, 95% CI 1.12-12.94, p = 0.033), treatment with methotrexate (OR: 2.55, 95% CI: 1.56-4.17, p < 0.001), poor global physical health (OR: 1.07, 95% CI 1.00-1.15, p = 0.044) and mental health (OR: 0.91, 95% CI 0.87-0.95, p < 0.001) were independent factors associated disease flares in patients with RA. Our study highlights the impact of socio-demographic factors, clinical characteristics and mental health on disease flares in patients with RA. These insights may help determine relevant strategies to proactively manage RA patients at risk of flares.

Characteristics and risk factors of COVID-19 breakthrough infections in Idiopathic Inflammatory Myopathies: Results from the COVAD study.

OBJECTIVES: To explore prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIM) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. METHODS: A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after 2 vaccine doses. We compared BIs characteristics and severity among IIMs, other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HC). Multivariable Cox regression models assessed the risk factors for BI, severe BI and hospitalisations among IIMs. RESULTS: Among 9449 included response, BIs occurred in 1447 (15.3%) respondents, median age 44 years (IQR 21), 77.4% female, and 182 BIs (12.9%) occurred among 1406 IIMs. Multivariable Cox regression among IIMs showed age as a protective factor for BIs [Hazard Ratio (HR)=0.98, 95%CI = 0.97-0.99], hydroxychloroquine and sulfasalazine use were risk factors (HR = 1.81, 95%CI = 1.24-2.64, and HR = 3.79, 95%CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for severe BI (HR = 3.61, 95%CI = 1.09-11.8). Non-White ethnicity (HR = 2.61, 95%CI = 1.03-6.59) was a risk factor for hospitalisation. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIM = 6.0% vs AIRD = 1.8%, nrAID = 2.2%, and HC = 0.9%), intensive care unit admission (IIM = 2.2% vs AIRD = 0.6%, nrAID, and HC = 0%), advanced treatment with antiviral or monoclonal antibodies (IIM = 34.1% vs AIRD = 25.8%, nrAID = 14.6%, and HC = 12.8%), and had more hospitalisation (IIM = 7.7% vs AIRD = 4.6%, nrAID = 1.1%, and HC = 1.5%). CONCLUSION: Patients with IIMs are susceptible to severe COVID-19 BI. Age and immunosuppressive treatments were related to the risk of BIs.

New strategies in the diagnosis and treatment of immune-checkpoint inhibitor-mediated colitis.

Immune-checkpoint inhibitor-mediated colitis (IMC) is an increasingly recognized adverse event in cancer immunotherapy, particularly associated with immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 antibodies. As this revolutionary immunotherapy gains prominence in cancer treatment, understanding, diagnosing, and effectively managing IMC becomes paramount. IMC represents a unique challenge due to its immune-mediated nature and potential for severe complications. However, a precise picture of IMC pathophysiology is currently unavailable. Therefore, we aimed to summarize the existing data while acknowledging the need for further research. This comprehensive review explores the mechanisms underlying ICIs, gastrointestinal adverse effects, and, in particular, IMC's incidence, prevalence, and features. Our review also emphasizes the importance of recognizing IMC's distinct clinical and histopathological features to differentiate it from other forms of colitis. Furthermore, this paper highlights the urgent need for evolving diagnostic methods, therapeutic strategies, and a multidisciplinary approach to effectively manage IMC.

Navigating the Cytokine Seas: Targeting Cytokine Signaling Pathways in Cancer Therapy.

Cancer remains one of the leading causes of morbidity and mortality worldwide, necessitating continuous efforts to develop effective therapeutic strategies. Over the years, advancements in our understanding of the complex interplay between the immune system and cancer cells have led to the development of immunotherapies that revolutionize cancer treatment. Cytokines, as key regulators of the immune response, are involved in both the initiation and progression of cancer by affecting inflammation and manipulating multiple intracellular signaling pathways that regulate cell growth, proliferation, and migration. Cytokines, as key regulators of inflammation, have emerged as promising candidates for cancer therapy. This review article aims to provide an overview of the significance of cytokines in cancer development and therapy by highlighting the importance of targeting cytokine signaling pathways as a potential therapeutic approach.

Meteorin-like Protein and Zonulin in Polycystic Ovary Syndrome: Exploring Associations with Obesity, Metabolic Parameters, and Inflammation.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a prevalent hormonal and metabolic disorder, wherein the adipose tissue and gut microbiome have been demonstrated to contribute to its pathogenesis. This study aims to assess the concentrations of the adipokine, meteorin-like protein (Metrnl) and the protein, zonulin, related to intestine permeability, in individuals with PCOS with a particular emphasis on their relationship with obesity, clinical manifestations, hormonal profiles, and metabolic parameters. METHODS: A cohort comprising 58 women with PCOS, classified according to the Rotterdam criteria, was enrolled. The study also considered age, body mass index (BMI), and ethnicity-matched controls (n = 30). Comprehensive anthropometric and clinical evaluations, hormonal assays, and biochemical analyses were conducted during the follicular phase. Subsequent subgroup analyses were executed within the PCOS cohort based on waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum concentrations of Metrnl and zonulin were quantified via the enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: The Metrnl and zonulin levels exhibited no significant disparity between PCOS patients and controls. Nevertheless, within the entire participant cohort and the PCOS group exclusively, overweight/obese participants demonstrated higher Metrnl concentrations relative to their normal-weight counterparts (p < 0.001, p = 0.001, respectively). Furthermore, higher Metrnl concentrations were identified in subgroups characterized by high WHtR and IR in comparison to those with low WHtR (p = 0.001) and without IR (p = 0.001), respectively. A correlation emerged between Metrnl levels and various anthropometric and metabolic parameters, as well as sex-hormone-binding globulin (SHBG) and interleukin-18 (IL-18) within the PCOS group. Multiple linear regression analysis identified HOMA-IR as the sole independent predictor of Metrnl levels. CONCLUSION: While Metrnl and zonulin levels do not serve as diagnostic indicators of PCOS, elevated Metrnl concentrations exhibited robust associations with proinflammatory and metabolic irregularities within the PCOS population.

Flares in IIMs and the timeline following COVID-19 vaccination: a combined analysis of the COVAD-1 and -2 surveys.

OBJECTIVES: Disease flares in the post-coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). METHODS: The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models. RESULTS: Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7-235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P < 0.001) were associated with disparity between self-reported and IS-denoted flares. CONCLUSION: A diagnosis of IIMs confers an equal risk of flares in the post-COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration.

Global disparities in the treatment of idiopathic inflammatory myopathies: results from an international online survey study.

OBJECTIVES: We aimed to explore current practice and interregional differences in the treatment of idiopathic inflammatory myopathies (IIMs). We triangulated these observations considering countries' gross national income (GNI), disease subtypes, and symptoms using patient-reported information. METHODS: A cross-sectional ancillary analysis of the 'COVID-19 vaccination in auto-immune disease' (COVAD) e-survey containing demographic characteristics, IIM subtypes (DM, PM, IBM, anti-synthetase syndrome [ASSD], immune-mediated necrotizing myopathy [IMNM], overlap myopathies [OM]), current symptoms (surrogate for organ involvement) and treatments (corticosteroids [CS], immunomodulators [IM], i.e. antimalarials, immunosuppressants [IS], IVIG, biologic treatments and targeted-synthetic small molecules). Treatments were presented descriptively according to continents, GNI, IIM and organ involvement, and associated factors were analysed using multivariable binary logistic regressions. RESULTS: Of 18 851 respondents from 94 countries, 1418 with IIM were analysed (age 61 years, 62.5% females). DM (32.4%), IBM (24.5%) and OM (15.8%) were the most common subtypes. Treatment categories included IS (49.4%), CS (38.5%), IM (13.8%) and IVIG (9.4%). Notably, treatments varied across regions, GNI categories (IS mostly used in higher-middle income, IM in lower-middle income, IVIG and biologics largely limited to high-income countries), IIM subtypes (IS and CS associated with ASSD, IM with OM and DM, IVIG with IMNM, and biologic treatments with OM and ASSD) and disease manifestations (IS and CS with dyspnoea). Most inter-regional treatment disparities persisted after multivariable analysis. CONCLUSION: We identified marked regional treatment disparities in a global cohort of IIM. These observations highlight the need for international consensus-driven management guidelines considering patient-centred care and available resources.

Type 1 diabetes, COVID-19 vaccines and short-term safety: Subgroup analysis from the global COVAD study.

AIMS/INTRODUCTION: Coronavirus disease 2019 (COVID-19) vaccinations have been proven to be generally safe in healthy populations. However, the data on vaccine safety in patients with type 1 diabetes are scarce. This study aimed to evaluate the frequency and severity of short-term (<7-day) adverse vaccination events (AEs) and their risk factors among type 1 diabetes patients. MATERIALS AND METHODS: This study analyzed data from the COVID-19 vaccination in Autoimmune Diseases (COVAD) survey database (May to December 2021; 110 collaborators, 94 countries), comparing <7-day COVID-19 vaccine AE among type 1 diabetes patients and healthy controls (HCs). Descriptive statistics; propensity score matching (1:4) using the variables age, sex and ethnicity; and multivariate analyses were carried out. RESULTS: This study analyzed 5,480 completed survey responses. Of all responses, 5,408 were HCs, 72 were type 1 diabetes patients (43 females, 48.0% white European ancestry) and Pfizer was the most administered vaccine (39%). A total of 4,052 (73.9%) respondents had received two vaccine doses. Patients with type 1 diabetes had a comparable risk of injection site pain, minor and major vaccine AEs, as well as associated hospitalizations to HCs. However, type 1 diabetes patients had a higher risk of severe rashes (3% vs 0.4%, OR 8.0, 95% confidence interval 1.7-36), P = 0.007), although reassuringly, these were rare (n = 2 among type 1 diabetes patients). CONCLUSIONS: COVID-19 vaccination was safe and well tolerated in patients with type 1 diabetes with similar AE profiles compared with HCs, although severe rashes were more common in type 1 diabetes patients.

COVID-19 breakthrough infections in type 1 diabetes mellitus: a cross-sectional study by the COVID-19 Vaccination in Autoimmune Diseases (COVAD) Group.

To investigate the frequency, profile, and severity of COVID-19 breakthrough infections (BI) in patients with type I diabetes mellitus (T1DM) compared to healthy controls (HC) after vaccination. The second COVID-19 Vaccination in Autoimmune Diseases (COVAD-2) survey is a multinational cross-sectional electronic survey which has collected data on patients suffering from various autoimmune diseases including T1DM. We performed a subgroup analysis on this cohort to investigate COVID-19 BI characteristics in patients with T1DM. Logistic regression with propensity score matching analysis was performed. A total of 9595 individuals were included in the analysis, with 100 patients having T1DM. Among the fully vaccinated cohort, 16 (16%) T1DM patients had one BI and 2 (2%) had two BIs. No morbidities or deaths were reported, except for one patient who required hospitalization with oxygen without admission to intensive care. The frequency, clinical features, and severity of BIs were not significantly different between T1DM patients and HCs after adjustment for confounding factors. Our study did not show any statistically significant differences in the frequency, symptoms, duration, or critical care requirements between T1DM and HCs after COVID-19 vaccination. Further research is needed to identify factors associated with inadequate vaccine response in patients with BIs, especially in patients with autoimmune diseases.

Correlates of breakthrough COVID-19 in vaccinated patients with systemic sclerosis: survival analysis from a multicentre international patient-reported survey.

This study aimed to assess the incidence, predictors, and outcomes of breakthrough infection (BI) following coronavirus disease (COVID-19) vaccination in patients with systemic sclerosis (SSc), a risk group associated with an immune-suppressed state and high cardiopulmonary disease burden. Cross-sectional data from fully vaccinated respondents with SSc, non-SSc autoimmune rheumatic diseases (AIRDs), and healthy controls (HCs) were extracted from the COVAD database, an international self-reported online survey. BI was defined according to the Centre for Disease Control definition. Infection-free survival was compared between the groups using Kaplan-Meier curves with log-rank tests. Cox proportional regression was used to assess the association between BI and age, sex, ethnicity, and immunosuppressive drugs at the time of vaccination. The severity of BI in terms of hospitalization and requirement for oxygen supplementation was compared between groups. Of 10,900 respondents, 6836 fulfilled the following inclusion criteria: 427 SSc, 2934 other AIRDs, and 3475 HCs. BI were reported in 6.3% of SSc, 6.9% of non-SSc AIRD, and 16.1% of HCs during a median follow-up of 100 (IQR: 60-137) days. SSc had a lower risk for BI than HC [hazard ratio (HR): 0.56 (95% CI 0.46-0.74)]. BIs were associated with age [HR: 0.98 (0.97-0.98)] but not ethnicity or immunosuppressive drugs at the time of vaccination. Patients with SSc were more likely to have asymptomatic COVID-19, but symptomatic patients reported more breathlessness. Hospitalization [SSc: 4 (14.8%), HCs: 37 (6.6%), non-SSc AIRDs: 32(15.8%)] and the need for oxygenation [SSc: 1 (25%); HC: 17 (45.9%); non-SSc AIRD: 13 (40.6%)] were similar between the groups. The incidence of BI in SSc was lower than that in HCs but comparable to that in non-SSc AIRDs. The severity of BI did not differ between the groups. Advancing age, but not ethnicity or immunosuppressive medication use, was associated with BIs.

Cardiovascular Manifestations of Multisystem Inflammatory Syndrome in Children: A Single-Center Bulgarian Study.

Background and objectives: Multisystem inflammatory syndrome in children (MIS-C) poses challenges to the healthcare system, especially with frequent heart involvement. The current retrospective observational study aims to summarize the type and degree of cardiovascular involvement in children with MISC and to find possible associations between laboratory, inflammatory, and imaging abnormalities and the predominant clinical phenotype using a cluster analysis. Material and methods: We present a retrospective observational single-center study including 51 children meeting the MIS-C criteria. Results: Fifty-three percent of subjects presented with at least one sign of cardiovascular involvement (i.e., arterial hypotension, heart failure, pericardial effusion, myocardial dysfunction, pericarditis without effusion, myocarditis, coronaritis, palpitations, and ECG abnormalities). Acute pericarditis was found in 30/41 of the children (73%) assessed using imaging: 14/30 (46.7%) with small pericardial effusion and 16/30 (53.3%) without pericardial effusion. The levels of CRP were significantly elevated in the children with pericarditis (21.6 ± 13 mg/dL vs. 13.9 ± 11 mg/dL, p = 0.035), and the serum levels of IL-6 were higher in the children with small pericardial effusion compared to those without (191 ± 53 ng/L vs. 88 ± 27 ng/L, p = 0.041). Pericarditis with detectable pericardial effusion was significantly more frequent in the female vs. male subjects, 72% vs. 30% (p = 0.007). The hierarchical clustering analysis showed two clusters: Cluster 1 includes the children without cardiovascular symptoms, and Cluster 2 generalizes the MIS-C children with mild and severe cardiovascular involvement, combining pericarditis, myocarditis, heart failure, and low blood pressure. Also, subjects from Cluster 2 displayed significantly elevated levels of fibrinogen (5.7 ± 0.3 vs. 4.6 ± 0.3, p = 0.03) and IL-6 (158 ± 36 ng/mL vs. 66 ± 22 ng/mL, p = 0.032), inflammatory markers suggestive of a cytokine storm. Conclusions: Our results confirm that children with oligosymptomatic MIS-C or those suspected of long COVID-19 should be screened for possible cardiological involvement.

Role of Specific Autoantibodies in Neurodegenerative Diseases: Pathogenic Antibodies or Promising Biomarkers for Diagnosis.

Neurodegenerative diseases (NDDs) affect millions of people worldwide. They develop due to the pathological accumulation and aggregation of various misfolded proteins, axonal and synaptic loss and dysfunction, inflammation, cytoskeletal abnormalities, defects in DNA and RNA, and neuronal death. This leads to the activation of immune responses and the release of the antibodies against them. Recently, it has become clear that autoantibodies (Aabs) can contribute to demyelination, axonal loss, and brain and cognitive dysfunction. This has significantly changed the understanding of the participation of humoral autoimmunity in neurodegenerative disorders. It is crucial to understand how neuroinflammation is involved in neurodegeneration, to aid in improving the diagnostic and therapeutic value of Aabs in the future. This review aims to provide data on the immune system's role in NDDs, the pathogenic role of some specific Aabs against molecules associated with the most common NDDs, and their potential role as biomarkers for monitoring and diagnosing NDDs. It is suggested that the autoimmune aspects of NDDs will facilitate early diagnosis and help to elucidate previously unknown aspects of the pathobiology of these diseases.

Navigating the Challenges of Gluten Enteropathy and Infertility: The Role of Celiac-Related Antibodies and Dietary Changes.

Celiac disease (CD) is an autoimmune condition that is initiated in genetically susceptible individuals by the exposure of the intestines to gluten, and the early start of symptoms is related to malabsorption. Atypical variants of the illness are often identified in adulthood and are frequently associated with manifestations outside of the intestines, including metabolic osteopathy, anemia, and dermatitis herpetiformis. But also, empirical data suggest a correlation between CD and reproductive abnormalities, including repeated abortions. Infertility and repeated miscarriages frequently manifest in women diagnosed with CD and may serve as the initial clinical indication of a subclinical form. Furthermore, the condition may manifest as amenorrhea, infertility, and the delivery of infants with a low birth weight. Regarding the mechanisms of CD in infertility, along with the anti-tTG action to hinder the invasiveness of trophoblast, these antibodies could damage endometrial angiogenesis, which has been shown in in vitro models with human endometrial cells and in vivo in murine models. Another important aspect is the role of nutrient deficiencies, such as zinc deficiency (connected to impaired hormone production, secondary amenorrhea, and pre-eclampsia) and folic acid, etc. Therefore, our objective was to conduct a comprehensive review of the existing literature pertaining to this specific topic and to elucidate the role of the autoantibodies in its pathogenesis.

Applications of time series analysis in epidemiology: Literature review and our experience during COVID-19 pandemic.

Time series analysis is a valuable tool in epidemiology that complements the classical epidemiological models in two different ways: Prediction and forecast. Prediction is related to explaining past and current data based on various internal and external influences that may or may not have a causative role. Forecasting is an exploration of the possible future values based on the predictive ability of the model and hypothesized future values of the external and/or internal influences. The time series analysis approach has the advantage of being easier to use (in the cases of more straightforward and linear models such as Auto-Regressive Integrated Moving Average). Still, it is limited in forecasting time, unlike the classical models such as Susceptible-Exposed-Infectious-Removed. Its applicability in forecasting comes from its better accuracy for short-term prediction. In its basic form, it does not assume much theoretical knowledge of the mechanisms of spreading and mutating pathogens or the reaction of people and regulatory structures (governments, companies, etc.). Instead, it estimates from the data directly. Its predictive ability allows testing hypotheses for different factors that positively or negatively contribute to the pandemic spread; be it school closures, emerging variants, etc. It can be used in mortality or hospital risk estimation from new cases, seroprevalence studies, assessing properties of emerging variants, and estimating excess mortality and its relationship with a pandemic.

Blood Coagulation and Thrombotic Disorders following SARS-CoV-2 Infection and COVID-19 Vaccination.

Although abundant data confirm the efficacy and safety profile of the developed vaccines against COVID-19, there are still some concerns regarding vaccination in high-risk populations. This is especially valid for patients susceptible to thrombotic or bleeding events and hesitant people due to the fear of thrombotic incidents following vaccination. This narrative review focuses on various inherited and acquired thrombotic and coagulation disorders and the possible pathophysiologic mechanisms interacting with the coagulation system during immunization in view of the currently available safety data regarding COVID-19 vaccines. Inherited blood coagulation disorders and inherited thrombotic disorders in the light of COVID-19, as well as blood coagulation and thrombotic disorders and bleeding complications following COVID-19 vaccines, along with the possible pathogenesis hypotheses, therapeutic interventions, and imaging for diagnosing are discussed in detail. Lastly, the lack of causality between the bleeding and thrombotic events and COVID-19 vaccines is debated, but still emphasizes the importance of vaccination against COVID-19, outweighing the minimal risk of potential rare adverse events associated with coagulation.

Gender differences in patient experience in idiopathic inflammatory myopathies: Sub analysis from the COVAD dataset.

OBJECTIVES: We aimed to investigate gender-based differences in idiopathic inflammatory myopathies (IIMs), with a particular focus on patient-reported outcomes, utilizing data obtained through the international COVID-19 vaccination in autoimmune disease (COVAD) e-survey. METHODS: Patient-reported outcomes including fatigue, pain, and physical function were extracted from the COVAD database and compared between genders, adjusting for demographics and IIM subgroups by multivariable analysis. Inclusion body myositis (IBM) was analysed separately because of substantial differences in outcomes. RESULTS: 1197 complete responses from patients with IIMs as of 31 August 2021 were analysed. Seventy percent were women. Women were younger (58 [48-68] vs. 69 [58-75] years old, median [IQR], p < 0.001) and more likely to suffer from autoimmune multimorbidity, defined as three or more autoimmune diseases in an individual patient (11.4% vs. 2.8%, p < 0.001). In non-IBM IIMs, fatigue visual analogue scale scores were higher in women (5 [3-7] vs. 4 [2-6], median [IQR], p = 0.004), whereas no significant gender-based differences were noted in IBM. Multivariable analysis in non-IBM IIMs revealed women, residence in high-income countries, overlap myositis, and autoimmune multimorbidity were independently associated with increased fatigue. CONCLUSIONS: Women with IIMs suffer from autoimmune multimorbidity and experience increased fatigue compared to men.