Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) in 2023.

In 2011, a syndrome entitled ASIA (Autoimmune/inflammatory Syndrome Induced by Adjuvants; Shoenfeld's syndrome) was first described. ASIA aimed to organize under a single umbrella, the existing evidence regarding certain environmental factors which possess immune stimulatory properties, in order to shed light on a common pathway of autoimmune pathogenesis. Such environmental immune stimulators, or adjuvants, include among others: aluminum salts as in vaccines, various medical implants, as well as various infectious agents. After the launch of the ASIA syndrome, the expansion and recognition of this syndrome by different researchers from different countries began. During the past decades, evidence had been accumulating that (auto)immune symptoms can be triggered by exposure to environmental immune stimulatory factors that act as an adjuvant in genetically susceptible individuals. A panoply of unexplained subjective and autonomic-related symptoms has been reported in patients with ASIA syndrome. The current review summarizes and updates accumulated knowledge from the past decades, describing new adjuvants- (e.g. polypropylene meshes) and vaccine- (e.g. HPV and COVID vaccines) induced ASIA. Furthermore, a direct association between inflammatory/autoimmune diseases with ASIA syndrome, will be discussed. Recent cases will strengthen some of the criteria depicted in ASIA syndrome such as clear improvement of symptoms by the removal of adjuvants (e.g. silicone breast implants) from the body of patients. Finally, we will introduce additional factors to be included in the criteria for ASIA syndrome such as: (1) dysregulated non-classical autoantibodies directed against G-protein coupled receptors (GPCRs) of the autonomic nervous system and (2)) small fiber neuropathy (SFN), both of which might explain, at least in part, the development of 'dysautonomia' reported in many ASIA patients.

Risk Factors and Outcomes for COVID-19 in Autoimmune Inflammatory Diseases during the SARS-CoV-2 Pandemic: A Comparative Study.

BACKGROUND: Patients with autoimmune disease (AID) and coronavirus disease 2019 (COVID-19) could have higher mortality due to the co-morbidity and the use of immunosuppressive therapy. OBJECTIVES: To analyze the risk factors and outcomes of patients with AID and COVID-19 versus a control group. METHODS: A prospective cohort study included patients with and without AID and COVID-19. Patients were paired by age and sex. Clinical, biochemical, immunological treatments, and outcomes (days of hospital stay, invasive mechanical ventilation [IMV], oxygen at discharge, and death) were collected. RESULTS: We included 226 COVID-19 patients: 113 with AID (51.15 ± 14.3 years) and 113 controls (53.45 ± 13.3 years). The most frequent AIDs were Rheumatoid arthritis (26.5%), systemic lupus erythematosus (21%), and systemic sclerosis (14%). AID patients had lower lactate dehydrogenas, C-reactive protein, fibrinogen, IMV (P = 0.027), and oxygen levels at discharge (P ≤ 0.0001) and lower death rates (P ≤ 0.0001). Oxygen saturation (SaO2) ≤ 88% at hospitalization provided risk for IMV (RR [relative risk] 3.83, 95% confidence interval [95%CI] 1.1-13.6, P = 0.038). Higher creatinine and LDH levels were associated with death in the AID group. SaO2 ≤ 88% and CO-RADS ≥ 4 were risk factors for in-hospital mortality (RR 4.90, 95%CI 1.8-13.0, P = 0.001 and RR 7.60, 95%CI 1.4-39.7, P = 0.016, respectively). Anticoagulant therapy was protective (RR 0.36, 95%CI 0.1-0.9, P = 0.041). CONCLUSIONS: Patients with AID had better outcomes with COVID-19 than controls. Anticoagulation was associated with a lower death in patients with AID.

Autoimmune post-COVID vaccine syndromes: does the spectrum of autoimmune/inflammatory syndrome expand?

To date, around 60% of the world population has been protected by vaccines against SARS-CoV-2, significantly reducing the devastating effect of the pandemic and restoring social economic activity through mass vaccination. Multiple studies have demonstrated the effectiveness and safety of vaccines against COVID-19 in healthy populations, in people with risk factors, in people with or without SARS-CoV-2 infection, and in immunocompromised people. According to the criteria for post-vaccine adverse events established by the World Health Organization, a minority of individuals may develop adverse events, including autoimmune syndromes. The exact mechanisms for the development of these autoimmune syndromes are under study, and to date, a cause-effect relationship has not been established. Many of these autoimmune syndromes meet sufficient criteria for the diagnosis of Adjuvant-Induced Autoimmune Syndrome (ASIA syndrome). The descriptions of these autoimmune syndromes open new perspectives to the knowledge of the complex relationship between the host, its immune system, with the new vaccines and the development of new-onset autoimmune syndromes. Fortunately, most of these autoimmune syndromes are easily controlled with steroids and other immunomodulatory medications and are short-lived. Rheumatologists must be alert to the development of these autoimmune syndromes, and investigate the relationship between autoimmune/inflammatory symptoms and vaccination time, and assess their therapeutic response.

Two Cases of Graves' Disease Following SARS-CoV-2 Vaccination: An Autoimmune/Inflammatory Syndrome Induced by Adjuvants.

Background: The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) comprises four entities, including the postvaccination phenomenon, which appears after being exposed to adjuvants in vaccines that increase the immune response. There is limited information about autoimmune endocrine diseases and ASIA after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Patient's Findings: Two female health care workers received a SARS-CoV-2 vaccine, and three days later developed clinical manifestations of thyroid hyperactivity, with increased thyroid hormone levels on thyroid function tests, suppressed thyroid-stimulating hormone, and elevated antithyroid antibodies. Summary: Vaccines have been shown to trigger an immune response that leads to a broad spectrum of autoimmune diseases, including autoimmune thyroid disease. Our patients met the diagnostic criteria for ASIA; they were exposed to an adjuvant (vaccine), and they developed clinical manifestations of thyroid hyperfunction within a few days, with the appearance of antithyroid antibodies, despite being healthy before vaccination. Conclusion: Graves' disease can occur after SARS-CoV-2 vaccination.