ABSTRACT
Allergic and hypersensitivity reactions induced by COVID-19 vaccines are increasingly reported and some patients may develop prolonged urticarial reactions following COVID-19 vaccination. Herein, we investigated the risk factors and immune mechanisms for patients with COVID-19 vaccines-induced immediate allergy and chronic urticaria (CU). We prospectively recruited and analyzed 129 patients with COVID-19 vaccine-induced immediate allergic and urticarial reactions as well as 115 COVID-19 vaccines-tolerant individuals from multiple medical centers during 2021-2022. The clinical manifestations included acute urticaria, anaphylaxis, and delayed to chronic urticaria developed after COVID-19 vaccinations. The serum levels of histamine, IL-2, IL-4, IL-6, IL-8, IL-17A, TARC, and PARC were significantly elevated in allergic patients comparing to tolerant subjects (P-values=4.5x10-5-0.039). Ex vivo basophil revealed that basophils from allergic patients could be significantly activated by COVID-19 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P-values from 3.5x10-4 to 0.043). Further BAT study stimulated by patients' autoserum showed positive in 81.3% of patients with CU induced by COVID-19 vaccination (P=4.2x10-13), and the reactions could be attenuated by anti-IgE antibody. Autoantibodies screening also identified the significantly increased of IgE-anti-IL-24, IgG-anti-FceRI, IgG-anti-TPO, and IgG-anti-thyroid-related proteins in COVID-19 vaccines-induced CU patients comparing to SARS-COV-2 vaccines-tolerant controls (P-values= 4.6x10-10-0.048). Patients with COVID-19 vaccines-induced recalcitrant CU patients could be successfully treated with anti-IgE therapy. In conclusion, our results revealed that multiple vaccine components, inflammatory cytokines, and autoreactive IgG/IgE antibodies contribute to COVID-19 vaccine-induced immediate allergic and autoimmune urticarial reactions (Minor revision in Journal of Autoimmunity [IF=14.551]).Copyright © 2023
ABSTRACT
Case report Background: It is well known that chronic spontaneous urticaria (CSU) has an autoimmune etiology in 40% of cases. It is often comorbid with other autoimmune diseases and a wide spectrum of autoantibodies involved in the pathogenesis of CSU is discussed. Objective(s): We share a clinical case of a rare underline autoimmune disease with later onset of CSU and chronic induced urticaria (CIU). Case: A 38-year- old woman was admitted to the hospital with SARS-CoV- 2 infection. At the age of 22, she was diagnosed with Takayasu's disease involving the aorta, the common and external carotid artery, and the left subclavian artery. Surgical interventions were performed twice -angioplasty of the involved vessels, but in both cases restenosis of the affected arteries was observed. Regarding the underlying disease, the patient received 10 mg of methotrexate once a week and 20 mg of prednisone daily. Due to detailed history collection, the patient noted that for the last 4 months she has rashes, bright red in color, rising above the surface of the skin and accompanied by a strong burning and itching dominantly on the upper and lower extremities, trunk. Appearing every day spontaneously, they have a rounded shape (diameter of up to 40-50 mm). While liner scratching the rash has similar contour. Rash elements disappear within a few hours, do not leave traces. During the current hospitalization, a wheal element up to 40 mm in diameter was observed at the wrist area, stayed for a few hours. UAS-7 -42. According to examination: eosinophils 1000 cells/mcl (patient noticed that eosinophilia of the blood has happened before, an examination was conducted, helminthiasis and parasitosis were excluded), total IgE -more than 2000 IU/ml, antibodies to b2-glycoprotein were revealed. Freak test -negative, but the linear wheals were confirmed by retrospective photos. Result(s): In this clinical case, CSU occurs in combination with induced dermographic urticaria. This patient has extremely aggressive urticaria according to its frequency of occurrence despite therapy with systemic GCS and methotrexate. After recovery from coronavirus infection, further examination and consideration of the appointment of biologicals(anti-IgE) is planned.
ABSTRACT
Background-Aim: A 46 years old housewife patient with a bachelor's degree in Law contracted Covid-19 at the end of March 2021. She had a flu-like form with associated asthenia and drowsiness and no lack of sense of smell. It has been resolved in 25 days. Later, she developed progressive immediate memory loss, word-finding issues, motor and thinking slowing down. Methods: CT brain scan appeared as within the norm as well as liver enzymes, TSH, Vitamin B12, Folate and Rapid Plasma Reagine. Anti- ENA DNA ANA HIV TPO TG were negative too. In October, the patient had a further neuropsychological assessment that showed an overall picture characterized by partial orientation to space, working memory disorders, writing and comprehension (of complex tasks) issues, and immediate memory loss (possible sign both of attention span and concentration reduction). The auto-antibodies were assessed in November and they resulted negative. Moreover, the brain MRI scan and EEG (dated at the end of November) were both within the range. CSF neurodegenerative biomarkers and anti-neuronal antibodies appeared in the norm too. Results: Ultimately, in December 2021 she underwent an 18F-FDG PET brain scan and the SPM analysis showed an extensive hypometabolism in the bilateral frontal cortex and bilateral straight gyrus. Spared the cingulate cortex. Conclusions: The patient contracted Covid in March 2021. She developed neurological deterioration identified by FDG-PET. Negative autoantibodies and CSF biomarkers. PET scan was the only exam to define the brain damage in the patient above. Symmetrical bilateral frontal cortex and bilateral straight gyrus hypo-metabolism have been observed, the last one at the direct level of the olfactory bulb. In this area, in patients who died from Covid-19 it has been histologically demonstrated (data to be published) the presence of cellular inclusions named Corpore Amylacea. They would be a small hyaline mass that functions as a waste container that accumulates in the human brain in aging and in neurodegenerative and infectious processes. It is hypothesized to be that it can be involved in a sort of brain cleaning process1. Recently it has been described that they contain some neoepitopes that are recognized by natural IgMs, revealing a possible link between them and the natural immune system2. However, to now in our patient, the only diagnostic tool to evaluate the brain condition has been the 18F-FDG PET.
ABSTRACT
The basophil activation test (BAT) is a flow cytometric assay that evaluates the percentage of activation or degranulation of peripheral blood basophils, after “in vitro” exposure to specific allergens. In sensitized patients, the stimulation of peripheral blood basophils with a specific allergen induces or up-regulates the expression of molecules, such as CD63 and CD203c, which represent, markers of degranulation and activation of basophils, respectively. The validity of the BAT requires a negative control (sterile saline) and a positive control (anti-IgE molecules). Several studies have demonstrated the role of the BAT in supporting the diagnosis of drug, food and hymenoptera venom allergy. The BAT has shown a low sensitivity but good specificity in diagnosing allergy to drugs such as NSAIDs, beta-lactam antibiotics, quinolones and muscle relaxants. In food allergy, the sensitivity and specificity of the BAT depends on the food;in the case of peanut allergy the sensitivity reaches 96% while the specificity the 100%. In addition, the BAT is an useful tool to monitor the natural resolution of allergies and the clinical effects induced by either immunotherapy or anti-IgE treatment. Finally, the BAT has been utilized to study the pathogenetic mechanisms underlying several IgE-mediated diseases. For example, in patients affected by severe bronchial asthma, the BAT has demonstrated the ability of Staphylococcus aureus enterotoxins to induce the activation of basophils supporting the role of these enterotoxins as “triggers” of the inflammatory cascade in bronchial asthma. In patients with cystic fibrosis the BAT can be used to dis-criminate allergic bronchopulmonary aspergillosis from Aspergillus colonization. More recently, the BAT has been demonstrated as a potential diagnostic tool to evaluate allergy to the polyethylene glycol (PEG) present in the anti-SARS-CoV-2 BNT162b2 mRNA vaccine.
ABSTRACT
Background: Under the restriction of direct access to specialized health care, COVID-19 pandemic, has created an “iceberg” regarding disease control data in severe Bronchial Asthma (BA). We aimed to evaluate indicators of asthma control, in severe persistent BA, consequences of pandemic and in-person visits limitations among this patient population. Method: A cross-sectional study, obtained data from 86 patients with yearly pre-pandemic hospitalizations, at the only tertiary hospital center for severe persistent BA in Albania. Descriptive data analysis was performed through anamnestic and clinical records. Standardized and validated questionnaires for inhalers adherence and asthma control, have been performed though phone interview during January 2021. Patients under treatment with biologic drugs (anti-IgE) and allergen specific immunotherapy have been excluded. Results: 64% were classified as high TH2 phenotype, predominating late-onset eosinophilic asthma (30.2%), and in low TH2 phenotype, with predominance of obesity associated asthma (18.6 %). 66,3 % were females with mean age of 49.3 ± 13.9. Overall Asthma Control Test (ACT= 19.5 ± 3.8), 43% controlled (20-25 points), with no statistically significant differences, between sex and phenotypes. Among early onset allergic asthma phenotype (25,6%), lower ACT score (18.5 ± 1.5) resulted in outdoor + indoor allergen polysensitization, compared to monosensitization (p < 0.05). Seasonal influenza vaccination rate was 16.2%, ACT score between vaccinated and unvaccinated groups, with significant difference (p = 0.03). Prevalence of confirmed COVID-19 was 15.1%, only 1,2% severe. ATC score, between confirmed or suspected post COVID-19 severe ABs and COVID-19 negative, was not statistically significant. Coexistence of sporadic and intentional nonadherence affected ACT score (p = 0.01), between controlled (ACT, 20-25) and uncontrolled group (ACT<20 points). Conclusion: Asthma control in severe persistent BA population was <50%, affected by sensitization profile, seasonal flu vaccination and type of non-adherence to inhalers. Differences of disease control in ACT score, were not statistically related with phenotype, sex or post COVID-19 infection condition. Particularly, Severe Persistent Bronchial Asthma needs a periodic specialist care to reach disease control and to lower the burden of indirect pandemic effects on disease progression.