Ioanna Koniari

Vaccines constitute the most effective medications in public health as they control and prevent the spread of infectious diseases and reduce mortality. Similar to other medications, allergic reactions can occur during vaccination. While most reactions are neither frequent nor serious, anaphylactic reactions are potentially life-threatening allergic reactions that are encountered rarely, but can cause serious complications. The allergic responses caused by vaccines can stem from activation of mast cells via Fcε receptor-1 type I reaction, mediated by the interaction between immunoglobulin E (IgE) antibodies against a particular vaccine, and occur within minutes or up to four hours. The type IV allergic reactions initiate 48 h after vaccination and demonstrate their peak between 72 and 96 h. Non-IgE-mediated mast cell degranulation via activation of the complement system and via activation of the Mas-related G protein-coupled receptor X2 can also induce allergic reactions. Reactions are more often caused by inert substances, called excipients, which are added to vaccines to improve stability and absorption, increase solubility, influence palatability, or create a distinctive appearance, and not by the active vaccine itself. Polyethylene glycol, also known as macrogol, in the currently available Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines, and polysorbate 80, also known as Tween 80, in AstraZeneca and Johnson & Johnson COVID-19 vaccines, are excipients mostly incriminated for allergic reactions. This review will summarize the current state of knowledge of immediate and delayed allergic reactions in the currently available vaccines against COVID-19, together with the general and specific therapeutic considerations. These considerations include: The incidence of allergic reactions and deaths under investigation with the available vaccines, application of vaccination in patients with mast cell disease, patients who developed an allergy during the first dose, vasovagal symptoms masquerading as allergic reactions, the COVID-19 vaccination in pregnancy, deaths associated with COVID-19 vaccination, and questions arising in managing of this current ordeal. Careful vaccine-safety surveillance over time, in conjunction with the elucidation of mechanisms of adverse events across different COVID-19 vaccine platforms, will contribute to the development of a safe vaccine strategy. Allergists' expertise in proper diagnosis and treatment of allergic reactions is vital for the screening of high-risk individuals.

Chronic inflammation is a well-established background process in many age-related diseases. Many recent studies investigate the use of various inflammatory biomarkers such as C-reactive protein (CRP), interleukin-6, and interleukin-1 as predictors of physical and cognitive performance among elders. The phenotype of frailty has also been associated with underlying inflammatory mechanisms. The aim of this article was to review the literature referring to the correlation of CRP serum levels and frailty in older individuals. We tried to identify all relevant publications regarding the relation of CRP as an index of frailty in the elderly and its potential use. Although many studies in the recent medical literature positively associate serum CRP levels and frailty in older individuals, some do not, and some raise some interesting questions and set the basis for future studies. The association of CRP and frailty in elder patients should be considered when clinicians interpret inflammatory biomarkers in various clinical settings in such patients. Well-designed, prospective clinical trials are warranted to better assess the role and pathophysiology of frailty in the elderly and its mechanisms as also the exact role of CRP as an inflammatory marker and as a prognostic index in this syndrome.

Coronary symptoms associated with conditions related to mast cell activation and inflammatory cell interactions, such as those involving T-lymphocytes and macrophages, further inducing allergic, hypersensitivity, anaphylactic, or anaphylactic insults, are currently referred to as the Kounis syndrome. Kounis syndrome is caused by inflammatory mediators released during allergic insults, post-inflammatory cell activation, and interactions via multidirectional stimuli. A platelet subset of 20% with high- and low-affinity IgE surface receptors is also involved in this process. Kounis syndrome is not just a single-organ but also a complex multisystem and multi-organ arterial clinical condition; it affects the coronary, mesenteric, and cerebral arteries and is accompanied by allergy–hypersensitivity–anaphylaxis involving the skin, respiratory, and vascular systems in the context of anesthesia, surgery, radiology, oncology, or even dental and psychiatric medicine; further, it has significantly influences both morbidity and mortality. Kounis syndrome might be caused by numerous and continuously increasing causes, with broad clinical symptoms and signs, via multi-organ arterial system involvement, in patients of any age, thereby demonstrating predominant anaphylactic features in terms of a wide spectrum of mast cell-association disorders. Cardiac symptoms, such as chest pain, coronary vasospasm, angina pectoris, myocardial infarction, stent thrombosis, acute cardiac failure, and sudden cardiac death associated with subclinical, clinical, acute, or chronic allergic reactions, constitute the clinical manifestations of this syndrome. Since its first description, a common pathway between allergic and non-allergic coronary events has been demonstrated. The hypothesis is based on the existence of a much higher degree of mast cell degranulation at plaque erosion or rupture sites compared with at the adjacent areas or even more distant segments in post-acute myocardial infarction of non-allergic etiology. Although mast cell activation, differentiation, and mediator release takes days or weeks, the mast cell degranulation may occur just before any acute coronary event, further resulting in coronary artery vasoconstriction and atheromatous plaque rupture. It seems that medications and natural molecules stabilizing the mast cell membrane as well as monoclonal antibodies protecting the mast cell surface can emerge as novel therapeutic modalities for acute coronary and cerebrovascular event prevention.

Diabetic retinopathy (DR) is considered as a diabetes-related complication that can render severe visual impairments and is also a risk factor for acquired blindness in both developed as well as developing countries. Through fibrovascular epiretinal membranes (ERMs), this condition can similarly lead to tractional retinal detachment. Laboratory efforts evaluating the DR pathogenesis can be provided by ocular vitreous fluid and ERMs resulting from vitrectomy. The clinical stages of DR are significantly associated with expression levels of certain chemokines, including monocyte chemotactic protein-1 (MCP-1) in the intraocular fluid. The MCP-1 is also a known potent chemotactic factor for monocytes and macrophages that can stimulate them to produce superoxide and other mediators. Following hyperglycemia, retinal pigmented epithelial (RPE) cells, endothelial cells, and Müller's glial cells are of utmost importance for MCP-1 production, and vitreous MCP-1 levels rise in patients with DR. Increased expression of the MCP-1 in the eyes can also play a significant role in the pathogenesis of DR. In this review, current clinical and laboratory progress achieved on the MCP-1 and the DR concerning neovascularization and inflammatory responses in vitreous and/or aqueous humor of DR patients was summarized. It was suggested that further exploration of the MCP-1/CCR2 axis association between clinical stages of DR and expression levels of inflammatory and angiogenic cytokines and chemokines, principally the MCP-1 might lead to potential therapies aiming at neutralizing antibodies and viral vectors.

Antiphospholipid syndrome (APLS) is a rare syndrome mainly characterized by several hyper-coagulable complications and therefore, implicated in the operated cardiac surgery patient. APLS comprises clinical features such as arterial or venous thromboses, valve disease, coronary artery disease, intracardiac thrombus formation, pulmonary hypertension and dilated cardiomyopathy. The most commonly affected valve is the mitral, followed by the aortic and tricuspid valve. For APLS diagnosis essential is the detection of so-called antiphospholipid antibodies (aPL) as anticardiolipin antibodies (aCL) or lupus anticoagulant (LA). Minor alterations in the anticoagulation, infection, and surgical stress may trigger widespread thrombosis. The incidence of thrombosis is highest during the following perioperative periods: preoperatively during the withdrawal of warfarin, postoperatively during the period of hypercoagulability despite warfarin or heparin therapy, or postoperatively before adequate anticoagulation achievement. Cardiac valvular pathology includes irregular thickening of the valve leaflets due to deposition of immune complexes that may lead to vegetations and valve dysfunction; a significant risk factor for stroke. Patients with APLS are at increased risk for thrombosis and adequate anticoagulation is of vital importance during cardiopulmonary bypass (CPB). A successful outcome requires multidisciplinary management in order to prevent thrombotic or bleeding complications and to manage perioperative anticoagulation. More work and reporting on anticoagulation management and adjuvant therapy in patients with APLS during extracorporeal circulation are necessary.