Anti-IL-5 Pathway Agents in Eosinophilic-Associated Disorders Across the Lifespan.

Monoclonal antibodies targeting interleukin (IL)-5 pathways have revolutionized the treatment expectations for eosinophilic-associated conditions, particularly in patients with respiratory involvement. Mepolizumab (IL-5 antagonist monoclonal antibody), benralizumab (IL-5 receptor blocker monoclonal antibody), and reslizumab (IL-5 antagonist monoclonal antibody) have collectively contributed to the overall improvement of the disease burden in various conditions. Eosinophilic asthma currently boasts the most robust evidence across all age groups: all three biologics are approved for adults (aged ≥18 years); mepolizumab is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) also in children (aged ≥ 6 years), while bernalizumab was recently approved by the FDA for patients aged ≥6 years in the USA. In chronic rhinosinusitis with nasal polyps, subcutaneous mepolizumab is the only anti-IL-5 therapy approved so far and can be used in adult patients (aged ≥18 years). For eosinophilic esophagitis, conflicting evidence surrounds both mepolizumab, reslizumab, and benralizumab, leading to non-approval of these agents by the FDA/EMA. Recently, mepolizumab was approved for eosinophilic granulomatosis with polyangiitis patients aged ≥6 years or older and for hypereosinophilic syndrome adult patients. A phase III trial proving noninferiority of benralizumab versus mepolizumab in eosinophilic granulomatosis with polyangiitis has been recently published, while evidence on reslizumab is scant. Overall, current evidence on anti-IL-5 biologics for eosinophilic-associated disorders is mostly focused on adults, whereas data for individuals aged under 18 years and over 65 years are scarce, resulting in a lack of evidence, particularly regarding efficacy, for the use of anti-IL-5 agents in these specific patient populations. This review addresses high-quality evidence from randomized controlled trials and real-world post-marketing studies regarding the use of anti-IL-5 therapies for eosinophilic-associated disorders across all age groups, spanning childhood, adulthood, and older age.

Dupilumab: a delayed response in asthmatic and atopic patients treated for chronic rhinosinusitis with nasal polyps.

PURPOSE: Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a common disease, which was previously approached with sinus surgery or systemic corticosteroids. The advent of biological therapies radically changed the approach to this disease. On the other hand, there is scarce scientific evidence of how specific subsets of patients respond to this treatment. METHODS: this is a monocentric, prospective study investigating the long-term efficacy on biweekly 300 mg dupilumab therapy in CRSwNP, prescribed to 61 patients. Patients were evaluated at baseline and every 2 months for the first 6 months, then at 9, 12, 16, 20 and 24 months. RESULTS: dupilumab proved to be an effective treatment, neatly improving both subjective and objective measurements in CRSwNP. The main finding of the study is the difference between specific subgroups of patients: while the overall response is similar, patients with Th2 comorbidities such as asthma and atopy tend to reach a stable response later, with the improvement ongoing even after 6 months of therapy, while non-asthmatic, non-atopic patients attain an earlier stability in response. CONCLUSIONS: dupilumab provides an excellent long-term control of CRSwNP, but the response in asthmatic and atopic patients appears to be different and delayed when compared to non asthmatic and non atopic ones.

The Dual Lens of Endoscopy and Histology in the Diagnosis and Management of Eosinophilic Gastrointestinal Disorders-A Comprehensive Review.

Eosinophilic Gastrointestinal Disorders (EGIDs) are a group of conditions characterized by abnormal eosinophil accumulation in the gastrointestinal tract. Among these EGIDs, Eosinophilic Esophagitis (EoE) is the most well documented, while less is known about Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), and Eosinophilic Colitis (EoC). The role of endoscopy in EGIDs is pivotal, with applications in diagnosis, disease monitoring, and therapeutic intervention. In EoE, the endoscopic reference score (EREFS) has been shown to be accurate in raising diagnostic suspicion and effective in monitoring therapeutic responses. Additionally, endoscopic dilation is the first-line treatment for esophageal strictures. For EoG and EoN, while the literature is more limited, common endoscopic findings include erythema, nodules, and ulcerations. Histology remains the gold standard for diagnosing EGIDs, as it quantifies eosinophilic infiltration. In recent years, there have been significant advancements in the histological understanding of EoE, leading to the development of diagnostic scores and the identification of specific microscopic features associated with the disease. However, for EoG, EoN, and EoC, precise eosinophil count thresholds for diagnosis have not yet been established. This review aims to elucidate the role of endoscopy and histology in the diagnosis and management of the three main EGIDs and to analyze their strengths and limitations, their interconnection, and future research directions.

Dupilumab Efficacy on Asthma Functional, Inflammatory, and Patient-Reported Outcomes across Different Disease Phenotypes and Severity: A Real-Life Perspective.

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation.

IgE response to Aed al 13 and Aed al 14 recombinant allergens from Aedes albopictus saliva in humans.

Background: Mosquito bite is normally associated with mild allergic responses, but severe localized or systemic reactions are also possible. Reliable tools for the diagnosis of mosquito allergy are still unavailable. Here, we investigated the IgE response to 3 potential salivary allergens identified in the saliva of the tiger mosquito Aedes albopictus. Methods: Serum from 55 adult individuals (28 controls and 27 allergic people), were analysed using an in-house Enzyme Linked ImmunoSorbent Assay (ELISA) against the Salivary Gland Extract (SGE) and the recombinant proteins albD7l2 (Aed al 2), albAntigen5-3 (Aed al 13) and albLIPS-2 (Aed al 14). Results: Fifteen of the 27 (56%) individuals having hypersensitive reactions to mosquito bites had IgE serum levels recognizing SGE. Negative sera did not show detectable levels of IgE targeting the SGE from the most common sympatric mosquito Culex pipiens. Among the positive individuals, 2 subjects displayed IgE targeting Aed al 2 (13%), while IgE recognizing Aed al 13 and Aed al 14 were detected in ten (67%) and seven (47%) individuals, respectively. Two sera from non-hypersensitive subjects had detectable levels of IgE targeting Aed al 13, suggesting possible cross-reaction with the homologue salivary proteins of multiple mosquito species or, more generally, of hematophagous insects. Conclusions: Our results indicate that Aed al 13 and Aed al 14 hold the potential to be developed as tools for the diagnosis of allergy to Ae. albopictus bites. Such tools would facilitate epidemiological studies on tiger mosquito allergy in humans and might foster the development of further protein-based assays to investigate cross-species allergies.

Personalized and Precision Medicine in Asthma and Eosinophilic Esophagitis: The Role of T2 Target Therapy.

The role of type 2 inflammation has been progressively associated with many diseases, including severe asthma, atopic dermatitis, nasal polyposis, eosinophilic granulomatosis with polyangiitis, and, recently, eosinophilic esophagitis. Despite this, the association between asthma and esophagitis is still poorly known, and this is probably because of the low prevalence of each disease and the even lower association between them. Nonetheless, observations in clinical trials and, subsequently, in real life, have allowed researchers to observe how drugs acting on type 2 inflammation, initially developed and marketed for severe asthma, could be effective also in treating eosinophilic esophagitis. For this reason, clinical trials specifically designed for the use of drugs targeted to type 2 inflammation were also developed for eosinophilic esophagitis. The results of clinical trials are presently promising and envisage the use of biologicals that are also likely to be employed in the field of gastroenterology in the near future. This review focuses on the use of biologicals for type 2 inflammation in cases of combined severe asthma and eosinophilic esophagitis.

Early increase in eosinophil count may predict long-term hypereosinophilia during dupilumab treatment: a 2-year observational study.

KEY POINTS: In a limited subset of patients, dupilumab-induced hypereosinophilia is persistent. Two-month follow-up eosinophil count may predict long-lasting hypereosinophilia.

Hypersensitivity reactions to anti-SARS-CoV-2 vaccines: Basophil reactivity to excipients.

Basophil activation test (BAT) can tackle multiple mechanisms underlying acute and delayed hypersensitivity to drugs and vaccines and might complement conventional allergy diagnostics but its role in anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-related hypersensitivity is ill-defined. Therefore, 89 patients with possible hypersensitivity (56 % with delayed mucocutaneous manifestations) to anti-SARS-CoV-2 vaccines were tested with BAT for Macrogol 3350, DMG-PEG 2000, PEG 20000, polysorbate-80 and trometamol and compared to 156 subjects undergoing pre-vaccine BAT. A positive BAT was associated with delayed reaction onset (p = 0.010) and resolution (p = 0.011). BAT was more frequently positive to DMG-PEG 2000 than to other excipients in both groups (p < 0.001). DMG-PEG 2000 reactivity was less frequent in vaccine-naïve (6 %) than vaccinated subjects (35 %, p < 0.001) and associated with mRNA-1273 vaccination. DMG-PEG 2000 BAT might therefore have a diagnostic role in subjects with delayed hypersensitivity reactions. Natural immunity might be a key player in basophil activation.

Heart Rate Variability in Subjects with Severe Allergic Background Undergoing COVID-19 Vaccination.

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination is the world's most important strategy for stopping the pandemic. Vaccination challenges the body's immune response and can be complicated by hypersensitivity reactions. The autonomic nervous system can modulate the inflammatory immune response, therefore constituting a potential marker to characterize individuals at high risk of hypersensitivity reactions. Autonomic nervous system functionality was assessed through measurement of the heart rate variability (HRV) in subjects with a history of severe allergic reactions and 12 control subjects. HRV parameters included the mean electrocardiograph RR interval and the standard deviation of all normal R-R intervals (SDNN). All measurements were performed immediately before the anti-SARS-CoV-2 vaccination. The median RR variability was lower in the study than in the control group: 687 ms (645-759) vs. 821 ms (759-902); p = 0.02. The SDNN was lower in the study group than in the control group: 32 ms (23-36) vs. 50 ms (43-55); p < 0.01. No correlation was found between age and the SDNN. Autonomic nervous system activity is unbalanced in people with a severe allergy background.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Focus on the Pathophysiological and Diagnostic Role of Viruses.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a heterogeneous, multiorgan and potentially life-threatening drug-hypersensitivity reaction (DHR) that occurs several days or weeks after drug initiation or discontinuation. DHRs constitute an emerging issue for public health, due to population aging, growing multi-organ morbidity, and subsequent enhanced drug prescriptions. DRESS has more consistently been associated with anticonvulsants, allopurinol and antibiotics, such as sulphonamides and vancomycin, although new drugs are increasingly reported as culprit agents. Reactivation of latent infectious agents such as viruses (especially Herpesviridae) plays a key role in prompting and sustaining aberrant T-cell and eosinophil responses to drugs and pathogens, ultimately causing organ damage. However, the boundaries of the impact of viral agents in the pathophysiology of DRESS are still ill-defined. Along with growing awareness of the multifaceted aspects of immune perturbation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the ongoing SARS-CoV-2-related disease (COVID-19) pandemic, novel interest has been sparked towards DRESS and the potential interactions among antiviral and anti-drug inflammatory responses. In this review, we summarised the most recent evidence on pathophysiological mechanisms, diagnostic approaches, and clinical management of DRESS with the aim of increasing awareness on this syndrome and possibly suggesting clues for future research in this field.

Case report: Successful use of mepolizumab for immune checkpoint inhibitors-induced hypereosinophilic syndrome in two patients with solid malignancies.

Hypereosinophilic syndrome (HES) represents a group of blood disorders characterized by an absolute eosinophil count (AEC) > 1.5 × 103/µl in the peripheral blood, which eventually extravasate and cause organ damage. It can be primary or secondary to infections or tumors. The infiltration of eosinophils in tissue and organs is associated with different disorders and, in some cases, with life-threatening manifestations. Albeit the pathogenesis of HES in patients with solid tumo\rs is not yet clarified; recently, HES has also been described as an immune-related adverse event in patients with solid tumors receiving immune checkpoint inhibitors. Treatment of HES is still debated, especially in patients with concomitant solid tumors, and different drugs including imatinib, hydroxyurea, interferon-ɑ, glucocorticoids, and the monoclonal antibody targeting circulating IL-5 mepolizumab have been proposed according to the underlying cause and the severity of HES. Herein, we describe, for the first time, the successful use of mepolizumab for the treatment of immune checkpoint-induced HES in two patients with metastatic solid tumor.

Predictors and outcomes of delirium in the emergency department during the first wave of the COVID-19 pandemic in Milan.

BACKGROUND: Respiratory infections can be complicated by acute brain failure. We assessed delirium prevalence, predictors and outcomes in COVID-19 ED patients. METHODS: This was a retrospective observational study conducted at the San Raffaele ED (Italy). Patients age >18 years attending the ED between 26 February 2020 and 30 May 2020 and who had a positive molecular nasopharyngeal swab for SARS-CoV-2 were included. The Chart-Based Delirium Identification Instrument (CHART-DEL) was used to retrospectively assess delirium. Univariable and multivariable logistic regression analyses were used to evaluate delirium predictors. Univariable binary logistic regression analyses, linear regression analyses and Cox regression analyses were used to assess the association between delirium and clinical outcomes. Age-adjusted and sex-adjusted models were then run for the significant predictors of the univariable models. RESULTS: Among the 826 included patients, 123 cases (14.9%) of delirium were retrospectively detected through the CHART-DEL method. Patients with delirium were older (76.9±13.15 vs 61.3±14.27 years, p<0.001) and more frequently living in a long-term health facility (32 (26%) vs 22 (3.1%), p<0.001). Age (OR 1.06, 95% CI 1.04 to 1.09, p<0.001), dementia (OR 17.5, 95% CI 7.27 to 42.16, p<0.001), epilepsy (OR 6.96, 95% CI 2.48 to 19.51, p<0.001) and the number of chronic medications (OR 1.09, 95% CI 1.01 to 1.17, p=0.03) were significant predictors of delirium in multivariable analyses. Delirium was associated with increased in-hospital mortality (adjusted HR 2.16, 95% CI 1.55 to 3.03, p<0.001) and with a reduced probability of being discharged home compared with being institutionalised (adjusted OR 0.39, 95% CI 0.25 to 0.61, p<0.001). CONCLUSIONS: Chart review frequently identified ED delirium in patients with COVID-19. Age, dementia, epilepsy and polypharmacy were significant predictors of ED delirium. Delirium was associated with an increased in-hospital mortality and with a reduced probability of being discharged home after hospitalisation. The findings of this single-centre retrospective study require validation in future studies.

Interactions between Severe Allergy and Anxiety in Anti-SARS-CoV-2 Vaccinees.

Severe drug allergy affects patient hesitancy to new treatments, posing unprecedented challenges to anti-SARS-CoV-2 vaccination campaigns. We aimed to analyze the psychological profile of vaccinees with a history of severe allergy in comparison to subjects with a milder allergy history. Patients attending a dedicated vaccination setting were administered an anonymized questionnaire including clinical data and the State-Trait Anxiety Inventory (STAI) scale (score range 20−80). Patients were also asked whether being in a protected setting affected their attitude toward vaccination. Data are expressed as median (interquartile range). We enrolled 116 patients (78% women), of whom 79% had a history of drug anaphylaxis. The median state anxiety score was 36.5 (30−47.2), while the trait anxiety score was 37 (32−48). State anxiety was higher in those with severe than mild allergy [39 (32−50) vs. 30 (25−37); p < 0.001], with the highest score found in a patient with previous drug anaphylaxis (42.5 [32−51.7]). More than 50% of patients reported that being in a protected setting had lowered their anxiety. Severe allergy is associated with a higher burden of situational anxiety in the setting of vaccination without affecting patient constitutional (trait) levels of anxiety. Vaccination in dedicated facilities might overcome issues related to hesitancy and improve patients' quality of life.

Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: a multicentric prospective study in real life.

BACKGROUND: Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies. Aim of the study was to evaluate the efficacy and safety of dupilumab in adult patients with CRSwNP stratified by common overlapping comorbid conditions. METHODS: We performed a multicenter, observational, prospective study enrolling adult patients with severe CRSwNP who had started dupilumab treatment in the context of standard care from January 2021 to October 2021. Data were collected from twentynine Italian secondary care centers for allergy and clinical immunology, all of which were part of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). A number of efficacy parameters were used. Patient data were compared using the Wilcoxon test for paired data. All statistical analyses were performed with SPSS version 20 (IBM, Armonk, NY, USA). RESULTS: In total, 82 patients with nasal polyposis were identified. A significant improvement was detected for all the applied efficacy parameters, i.e. 22-item Sino-Nasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp score (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the 1st second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) scores for AD. A non-significant improvement was also obtained in the Urticaria Activity Score over 7 days (UAS7) for chronic spontaneous urticaria. Treatment with dupilumab was well tolerated. CONCLUSIONS: These data suggest that dupilumab treatment in patients suffering from CRSwNP and associated comorbidities may be suitable. Such outcome, although confirmation by trials is warranted, suggests the possibility to treat different disorders with a single therapy, with favorable effects especially under the cost-effectiveness aspect.

Hypereosinophilia management in patients with type 2 chronic rhinosinusitis treated with dupilumab: preliminary results.

PURPOSE: Biological therapies are gaining relevance in the management of CRSwNP with few adverse events reported. Among these, dupilumab, an anti-IL4-Ra monoclonal antibody, is frequently associated with hypereosinophilia (HE) which usually remains silent and progressively resolves, although some cases of systemic involvement occurs. The aim of this paper is to describe our experience and propose a management flowchart for HE during therapy with dupilumab. METHODS: Patients with CRSwNP who satisfied EPOS2020 criteria for biological therapies were included in this prospective study. Each case was discussed in a multidisciplinary meeting with subsequent prescription of dupilumab; all patients were candidates to follow-up bi-monthly for 6 months, while additional blood tests were scheduled in the event of HE. RESULTS: A total of 21 patients with a mean age of 48.4 years were enrolled. Of these, 15 of 21 presented an asthma comorbidity and 9 of 21 ASA sensitivity. Four patients (19%) developed HE with AEC > 1.5 × 109/L, whereas it occurred in 9.5% (two patients) if considered AEC > 3 × 109/L. No cases of hypereosinophilic syndrome were recorded. Following our decision-making flowchart, two patients received short-term corticosteroid therapy, whereas the other two were only eligible for closer follow-up. CONCLUSIONS: During dupilumab therapy, HE may occur and should be considered benign when < 3 × 109/L in the absence of organ involvement. Conversely, in case of HE ≥ 3 × 109/L, an empirical approach with short-term corticosteroid therapy should be considered to debulk the blood from eosinophils and prevent potential organ involvement.

Basal Serum Diamine Oxidase Levels as a Biomarker of Histamine Intolerance: A Retrospective Cohort Study.

Background: Histamine Intolerance (HIT) is a multifaceted pseudoallergic disorder possibly due to defective histamine metabolism. Diamine oxidase (DAO) contributes to histamine degradation and can be measured in the serum. The role of DAO measurement in the diagnostic work-up of HIT still remains unclear, and conflicting results have been reported in the literature. Therefore, we aimed to evaluate the possible clinical usefulness and consistency of DAO value ranges as provided by the assay manufacturer and verify whether they could predict the response to treatment. Methods: We retrospectively analyzed 192 outpatients with HIT symptoms and measured serum DAO values at baseline. Patients were prescribed either with low-histamine diet and/or enzymatic supplementation according to symptom severity and re-evaluated six to eight months later. Patients were stratified into three groups according to DAO levels: <3 U/mL, 3−10 U/mL, and >10 U/mL. HIT severity was assessed on a scale of 1 to 5 before and after treatment. Results: A total of 146 patients completed the study. Gastrointestinal and cutaneous symptoms, often associated with headache, were more frequent in subjects with DAO < 10 U/mL. Symptom severity and DAO ranges were correlated. Patients with intermediate DAO levels (3−10 U/mL) showed a more complex clinical phenotype but also a more significant improvement in symptom severity (score reduction 50%, interquartile range (IQR) = 33−60%) when compared to patients with low DAO (40%, IQR = 20−60%; p = 0.045) or high DAO (33%, IQR = 0−50%; p < 0.001). Complex clinical phenotypes were also more frequent in patients with intermediate DAO levels. Conclusions: HIT is characterized by typical symptoms and low levels of DAO activity. Symptom severity was associated with the degree of DAO deficiency. Patients with DAO values between 3 and 10 U/mL show the best response to treatment (low-histamine diet and/or DAO supplementation). DAO value could arguably be considered as a predictor of clinical response to treatment. Prospective studies are needed to confirm these data.

A prospective study on the efficacy of dupilumab in chronic rhinosinusitis with type 2 inflammation.

Objective: Treatment for chronic rhinosinusitis with nasal polyps (CRSwNP) includes endoscopic sinus surgery and topic and/or systemic corticosteroids, which have only temporary effects. The development of biologic therapies has provided a new treatment paradigm for CRSwNP. Dupilumab is the only biological approved in Italy for CRSwNP, but its efficacy in a real-life context is still scarce. Methods: We carried out a monocentric prospective study at our institution with a 6-month follow-up on patients administered biweekly 300 mg dupilumab therapy for CRSwNP, prescribed according to EPOS 2020 criteria. Patients were evaluated at baseline and every 2 months. Results: Median values at baseline and 6 months were, respectively, 3/12 and 8/12 for the Brief Smell Identification Test (p = 0.005), 5/8 and 2/8 for the Nasal Polyp Score (p < 0.001), 10/20 and 6/20 for the Lund-Kennedy score (p < 0.001), 65/110 and 14/110 for the Sinonasal Outcome Test (p < 0.001), and 15/25 and 23/25 for the Asthma Control Test score (p = 0.009). Adverse events were mild, consisting mainly in discomfort at the site of injection. Four patients developed asymptomatic hypereosinophilia. The treatment was not discontinued in any patient. Conclusions: Dupilumab was confirmed to be an effective and safe treatment for CRSwNP, as previously seen in registrational studies.

Challenges to Vaccination against SARS-CoV-2 in Patients with Immune-Mediated Diseases.

Aberrant deployment of the immune response is a hallmark pathogenic feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease (COVID-19), possibly accounting for high morbidity and mortality, especially in patients with comorbidities, including immune-mediated disorders. Immunisation with SARS-COV-2 vaccines successfully instructs the immune system to limit viral spread into tissues, mitigate COVID-19 manifestations and prevent its most detrimental inflammatory complications in the general population. Patients with immune-mediated diseases have been excluded from vaccine registration trials, foreclosing the acquisition of specific efficacy and safety data. In this review, we aimed to summarise and critically discuss evidence from real-world studies addressing this issue to provide a comprehensive view of the impact of vaccination practices in patients with allergy, autoimmunity or immunodeficiency. We analysed clinical and laboratory data from 34 studies involving more than 13,000 subjects with various immune disorders who were vaccinated with mRNA- DNA- or inactivated viral particle-based vaccines. These data globally support the safe and effective use of SARS-CoV-2 vaccines in patients with immune-mediated diseases, although patient-tailored strategies to determine vaccination timing, vaccine choice and background therapy management are warranted to optimise vaccination outcomes. More data are needed regarding patients with primary immunodeficiencies.

Efficacy of a rational algorithm to assess allergy risk in patients receiving the BNT162b2 vaccine.

Among 6146 hospital employees, 118 subjects with severe allergic background were identified through a screening questionnaire and stratified into 3 groups (Low-risk (LR), Intermediate (IR) and High-risk (HR) group), based on their allergic anamnesis. Data reports on hypersensitivity reactions (HypR) have been collected in both allergic and non-allergic subjects. Seventeen patients (14%) in the allergic population had a HypR after the first, the second or both doses. Skin manifestations were the most frequent ones. Allergic events were more frequent in HR (35%) than IR (10%; p = 0.005) or LR (0%; p = 0.074) subjects. No patient had anaphylaxis. All patients completed the vaccination schedule. 13 HypR occurred in patients without severe allergic background (13/6028, 0,2%) including one (1/6148, 0.016% of total population) WAO grade-4 anaphylaxis. Our data suggest that BNT162b2 mRNA Covid-19 vaccine is relatively safe also in patients with severe allergic background; however, some precautions are required for high-risk patients.