Intradermal skin test with mRNA vaccines as a surrogate marker of T cell immunity in immunocompromised patients.

OBJECTIVES: Intradermal skin test (IDT) with mRNA vaccines may represent a simple, reliable, and affordable tool to measure T cell response in immunocompromised patients who failed to mount serological responses following vaccination with mRNA covid-19 vaccines. METHODS: We compared anti-SARS-CoV-2 antibodies and cellular responses in vaccinated immunocompromised patients (n = 58), healthy seronegative naive controls (NC, n = 8), and healthy seropositive vaccinated controls (VC, n = 32) by Luminex, spike-induced IFN-γ Elispot and an IDT. A skin biopsy 24 h after IDT and single-cell RNAseq was performed in three vaccinated volunteers. RESULTS: Twenty-five percent of seronegative NC had a positive Elispot (2/8) and IDT (1/4), compared to 95% (20/21) and 93% (28/30) in seropositive VC, respectively. Single-cell RNAseq data in the skin of VC showed a predominant mixed population of effector helper and cytotoxic T cells. The TCR repertoire revealed 18/1064 clonotypes with known specificities against SARS-CoV-2, among which six were spike-specific. Seronegative immunocompromised patients with positive Elispot and IDT were in 83% (5/6) treated with B cell-depleting reagents, while those with negative IDT were all transplant recipients. CONCLUSIONS: Our results indicate that delayed local reaction to IDT reflects vaccine-induced T-cell immunity opening new perspectives to monitor seronegative patients and elderly populations with waning immunity.

Aeroallergen sensitization in school-age children with allergic rhinitis: What has changed during the COVID-19 pandemic?

BACKGROUND: Pandemic period may affect aeroallergen sensitization. OBJECTIVE: The study aimed to investigate changes in allergen sensitivities of skin prick test (SPT) in patients with allergic rhinitis (AR) during pandemic and to evaluate relationship with disease severity. METHODS: In all, 164 AR patients with or without asthma, aged 6-17 years, who have undergone SPTs prior to the pandemic and after October 1, 2021 (18th month of the pandemic), were evaluated retrospectively. The wheal size of allergens in performed SPTs during and prior to the pandemic were compared. Detected changes in allergen sensitivities via SPT results were compared with changes in the disease severity parameters (AR severity, asthma severity, and the number of asthma exacerbations per year), frequency of upper respiratory tract infections and antibiotic use, laboratory parameters, demographic characteristics, and visual analogue scores (VAS). RESULTS: House dust mites (HDMs), cat, pollen, Artemisia, and Cupressus sensitization increased in AR patients during the Coronavirus disease 2019 (COVID-19) pandemic. HDM, mold, and pollen wheal diameters increased in SPTs. Proportion of polysensitization increased during the pandemic, compared to pre-pandemic period (9.1% vs 3%; P < 0.001), and number of non-sensitized patients decreased during the pandemic period compared to the pre-pandemic period (7.9% vs 22.6%; P < 0.001). An increase in HDM sensitivity in SPTs was correlated with VAS for nasal blockage, and an increase in cat sensitivity was correlated with VAS for all nasal symptoms. CONCLUSION: We believe that inhalant allergen sensitization might have been affected by the lifestyle changes of patients during the pandemic. Hence, it is important to evaluate patients for allergen sensitization, especially patients with moderate/severe AR, to revise disease control measurements.

Basophil Activation Test with Different Polyethylene Glycols in Patients with Suspected PEG Hypersensitivity Reactions.

Allergic reactions to COVID-19 vaccine components are rare but should be considered. Polyethylene glycol (PEG) is responsible for anaphylaxis in mRNA vaccines. Skin tests have been used in the allergological work-up programs for COVID-19 vaccine evaluation. However, the reproducibility of the skin prick test is time-dependent and the reactivity declines over time. Therefore, we combined the administration of the skin tests with the basophil activation test (BAT) using PEG2000, PEG4000 and DMG-PEG2000, where the BAT was considered positive when the percentage of activated basophils was higher than 6%, 5% and 6.5%, for PEG 4000, PEG2000 and DMG-PEG2000, respectively. To this end, among the subjects that underwent allergy counseling at the Allergy Unit of our Institution during the 2020/2021 vaccination campaign, 13 patients had a suggested medical history of PEG/drug hypersensitivity and were enrolled together with 10 healthy donors. Among the enrolled patients 2 out of 13 tested patients were positive to the skin test. The BAT was negative in terms of the percentages of activated basophils in all analyzed samples, but the stimulation index (SI) was higher than 2.5 in 4 out of 13 patients. These data evidenced that, when the SI is higher than 2.5, even in the absence of positivity to BAT, the BAT to PEG may be a useful tool to be coupled to skin tests to evidence even low-grade reactions.

Cat allergy in children and the effect of the COVID-19 pandemic.

Background: Cat allergen is among the most common household allergens and can cause respiratory allergies and anaphylaxis in children. Objective: The aim of this study was to evaluate the characteristics of cat allergies in children and the impact of the coronavirus disease 2019 (COVID-19) pandemic on these characteristics. Methods: The study included pediatric patients with cat allergen sensitization demonstrated by skin-prick test (SPT) over a period of 2 years: 1 year before and 1 year during the pandemic. Demographic data, clinical features, and laboratory findings were evaluated from the patients' records. Results: Of 7428 SPTs performed, 566 patients (7.6%) were sensitized to cat allergen (56% boys; median age, 11 years). Fifty-eight percent of the patients (n = 329) presented during the pandemic period, 44.5% (n = 252) had symptoms with cat exposure, and 9% (n = 51/566) had anaphylaxis. Allergic rhinitis and asthma were present in 76% (n = 431) and 46.6% (n = 264) of the patients, respectively. When compared to prepandemic period, patients who presented during the pandemic had higher rates of cat sensitization (15% in pandemic group versus 4.4% in prepandemic group of all SPTs performed; p < 0.05), cat ownership (29.1% versus 13.9%; p < 0.001), and symptoms on cat exposure (51% versus 34%; p < 0.001). Factors that predicted symptom development in the patients who were cat sensitized were induration > 5 mm on SPT (odds ratio [OR] 1.9 [95% confidence interval {95% CI}], 1.1-3.2), cat ownership (OR 9.2 [95% CI, 4.9-17.3]), close contact with a cat owner (OR 7.1 [95% CI, 4-12]), allergic rhinitis (OR 3.1 [95% CI, 1.6-5.8]), conjunctivitis (OR 4.7 [95% CI, 2-10]), and atopic dermatitis (OR 2.2 [95% CI, 1-4.7]). Conclusion: We observed an increase in the prevalence of cat allergy among children during the COVID-19 pandemic. Care must be taken in terms of anaphylaxis in patients who were cat sensitized.

Simplifying the drug provocation test in non-immediate hypersensitivity reactions to amoxicillin in children: The experience of a tertiary care allergy unit.

BACKGROUND: Mild non-immediate reactions (NIR) to beta-lactams (ßLs) are the most common manifestation of adverse drug reactions in children, and the drug provocation test (DPT) remains the gold standard for diagnosis. However, there are still controversies about the protocol that should be used, especially regarding the administration of doses and the DPT length. OBJECTIVE: This study aimed to evaluate a pediatric population with a history of mild NIR to amoxicillin (AMX) or to amoxicillin-clavulanic acid (AMX/CL) who underwent a diagnostic workup including a DPT with the culprit drug, to understand if a graded DPT or, instead, a single full dose could be the most appropriate way of administration in clinical practice. METHODS: The data of children were retrospectively analyzed for a 5-year period, with demographic and clinical characteristics collected. We reported the allergy workup and the results of the DPT performed with the administration of incremental doses and a prolonged DPT at home for a total of 5 days. RESULTS: Three hundred fifty-four patients were included. Overall, 23/354 (6.5%) DPTs were positive: 11/23 patients showed a reaction after 2-8 h after the last dose on the 1st or 2nd day (1 reacted 30 min after the last dose), 1/23 reacted with urticaria 30 min after the first dose, 11/23 reacted at home on the 5th day of the DPT. CONCLUSION: This paper indirectly suggests that a single therapeutic dose administered on the 1st day of a DPT could be safe in the diagnostic workup of mild NIR to AMX/CL. Moreover, this could be less time-consuming as patients would spend less time in the hospital, also considering the public health restrictions imposed during the COVID-19 pandemic.

How to interpret skin prick tests and serum-specific IgE in children and young people with food allergy.

Food allergy is common, it can lead to significant morbidity andnegatively impacts on quality of life; therefore, it is vitally important we get the diagnosis right. However, making the diagnosis can be complex. Clinical history is the most important diagnostic tool and subsequent investigation may help confirm the diagnosis. The investigations available to most paediatric departments are skin prick testing and specific IgE so we will focus on these. Within this article we explore the evidence related to targeted testing and how to interpret these within the clinical context.

Cannabis-related allergies: An international overview and consensus recommendations.

Cannabis is the most widely used recreational drug in the world. Cannabis sativa and Cannabis indica have been selectively bred to develop their psychoactive properties. The increasing use in many countries has been accelerated by the COVID-19 pandemic. Cannabis can provoke both type 1 and type 4 allergic reactions. Officially recognized allergens include a pathogenesis-related class 10 allergen, profilin, and a nonspecific lipid transfer protein. Other allergens may also be relevant, and recognition of allergens may vary between countries and continents. Cannabis also has the potential to provoke allergic cross-reactions to plant foods. Since cannabis is an illegal substance in many countries, research has been hampered, leading to challenges in diagnosis since no commercial extracts are available for testing. Even in countries such as Canada, where cannabis is legalized, diagnosis may rely solely on the purchase of cannabis for prick-to-prick skin tests. Management consists of avoidance, with legal issues hindering the development of other treatments such as immunotherapy. Education of healthcare professionals is similarly lacking. This review aimed to summarize the current status of cannabis allergy and proposes recommendations for the future management of this global issue.

Utility and futility of skin testing to address concerns surrounding messenger RNA coronavirus disease 2019 vaccine reactions.

BACKGROUND: The mechanism of coronavirus disease 2019 (COVID-19) vaccine hypersensitivity reactions is unknown. COVID-19 vaccine excipient skin testing has been used in evaluation of these reactions, but its utility in predicting subsequent COVID-19 vaccine tolerance is also unknown. OBJECTIVE: To evaluate the utility of COVID-19 vaccine and vaccine excipient skin testing in both patients with an allergic reaction to their first messenger RNA COVID-19 vaccine dose and patients with a history of polyethylene glycol allergy who have not yet received a COVID-19 vaccine dose. METHODS: In this multicenter, retrospective review, COVID-19 vaccine and vaccine excipient skin testing was performed in patients referred to 1 of 3 large tertiary academic institutions. Patient medical records were reviewed after skin testing to determine subsequent COVID-19 vaccine tolerance. RESULTS: A total of 129 patients underwent skin testing, in whom 12 patients (9.3%) had positive results. There were 101 patients who received a COVID-19 vaccine after the skin testing, which was tolerated in 90 patients (89.1%) with no allergic symptoms, including 5 of 6 patients with positive skin testing results who received a COVID-19 vaccine after the skin testing. The remaining 11 patients experienced minor allergic symptoms after COVID-19 vaccination, none of whom required treatment beyond antihistamines. CONCLUSION: The low positivity rate of COVID-19 vaccine excipient skin testing and high rate of subsequent COVID-19 vaccine tolerance suggest a low utility of this method in evaluation of COVID-19 vaccine hypersensitivity reactions. Focus should shift to the use of existing vaccine allergy practice parameters, with consideration of graded dosing when necessary. On the basis of these results, strict avoidance of subsequent COVID-19 vaccination should be discouraged.

Alternative to In Vivo Tests During the COVID-19 Pandemic: Multiple Allergen Simultaneous Tests as a Useful First Screening.

BACKGROUND: In allergy diagnosis we sometimes find some clinical or logistic limitations to be able to carry out in vivo tests, so the detection of serum allergic-specific IgE could be an alternative as a first screening step. Here, we compare the results from the routine diagnostic tools and multiple allergen simultaneous tests to detect inhalant allergen sensitization. METHODS: Thirty-two subjects with a positive ImmunoCAP Phadiatop screening were included, evaluating the accuracy of their diagnosis using (1) specific IgE determination by ImmunoCAP and (2) MAST EUROLINE Immunoblot. RESULTS: The MAST method showed a high agreement and correlation with the ImmunoCAP system for Derma-tophagoides pteronyssinus, cat dander, orchard grass and Alternaria alternata. Of the subjects, 94% were sensitized to at least one of the allergens using MAST EUROLINE immunoblot, whereas 79% of individuals with a positive Phadiatop went undetected when we analyzed only the 4 allergens mentioned before. CONCLUSIONS: The study showed the usefulness of MAST EUROLINE immunoblot for screening detection of specific IgE antibodies directed against a broad spectrum of inhalant allergens as a first screening tool. Furthermore, its performance is not affected by the possible in vivo test limitations and avoids the arbitrary selection of allergenic sources for evaluation, which may lead to incorrect patients' diagnosis and management.

Allergic reactions to coronavirus disease 2019 vaccines and addressing vaccine hesitancy: Northwell Health experience.

BACKGROUND: Allergic and nonallergic adverse reactions have been reported with global coronavirus disease 2019 (COVID-19) vaccination. It was previously hypothesized that polyethylene glycol (PEG) may be responsible for anaphylactic reactions to messenger RNA (mRNA) COVID-19 vaccines. OBJECTIVE: To report the workflow established at our institution, types, and frequency of adverse reactions to mRNA COVID-19 vaccines in patients presenting for allergy evaluation. METHODS: A COVID-19 vaccine adverse reaction registry was established. We used PEG prick skin testing, followed by PEG challenges in selected cases, to ensure PEG tolerance and encourage completion of COVID-19 vaccination series. RESULTS: A total of 113 patients were included. Most vaccine reactions (86.7%) occurred in women. Anaphylaxis occurred only in women, all of which had a history of allergic disease and two-thirds had asthma. Anaphylaxis rate was 40.6 cases per million. None of the anaphylactic cases developed hypotension, required intubation, or required hospital admission. Systemic allergic symptoms, not fulfilling anaphylaxis criteria, were significantly more common in Pfizer-BioNTech than Moderna-vaccinated patients (P = .02). We observed a higher incidence of dermatologic nonurticarial reactions in men (P = .004). Among first-dose reactors, 86.7% received and tolerated the second dose. We observed a high rate of false-positive intradermal skin test results and frequent subjective symptoms with oral PEG challenge. CONCLUSION: Intradermal PEG testing has limited utility in evaluating anaphylaxis to mRNA vaccines. Most severe postvaccination allergic symptoms are not caused by hypersensitivity to PEG. Most people with reaction to the initial mRNA vaccine can be safely revaccinated. Patients with anaphylaxis to COVID-19 vaccines benefit from physician-observed vaccination.

Does aeroallergen sensitivity and allergic rhinitis in children cause milder COVID-19 infection?

Background: There are conflicting data with regard to the impact of respiratory and allergic comorbidities on the course of novel coronavirus disease 2019 (COVID-19) in children. Objective: This study aimed to investigate the relationship between allergic diseases and COVID-19 severity in pediatric patients. Methods: Seventy-five pediatric patients with COVID-19 were classified according to clinical severity and evaluated in the allergy/immunology and pulmonology departments 1 to 3 months after the infection resolved. Blood was collected from the patients for a complete blood cell count and assessment of immunoglobulin and total immunoglobulin E (IgE) levels, and skin-prick tests and spirometry tests were performed. Results: A total of 75 patients ages 5-18 years were evaluated. COVID-19 was asymptomatic/mild in 44 patients and moderate/severe/critical in 31 patients. Based on allergy evaluation, allergic rhinitis was diagnosed in 19 patients (25.3%), asthma in 10 patients (13%), and atopic dermatitis in 3 patients (4%). Aeroallergen sensitivity was detected in 26 patients (34.7%). COVID-19 infection was asymptomatic/mild in 15 patients with allergic rhinitis (78.9%) and in 21 with aeroallergen sensitivity (80.8%) (p = 0.038 and p = 0.005, respectively). There was no difference in severity between the patients with and without asthma (p = 0.550). The median (interquartile range) total IgE level was significantly higher in the asymptomatic/mild group (71.8 [30.7-211.2]) (p = 0.015). There were no differences in terms of spirometry parameters. Conclusion: Aeroallergen sensitization and allergic rhinitis in children may be associated with a milder course of COVID-19. The knowledge that atopy is associated with less-severe COVID-19 outcomes in children may guide clinical risk classification.

The Polysorbate containing AstraZeneca COVID-19 vaccine is tolerated by polyethylene glycol (PEG) allergic patients.

BACKGROUND: Polyethylene glycol (PEG) is the excipient found in the mRNA COVID-19 vaccines. We previously demonstrated PEG allergy was a cause of severe anaphylaxis to the Pfizer/BioNTech COVID-19 vaccine. PEG is widely used in many household products, cosmetics and medicines. However PEG allergy is rare, there have been few confirmed cases of PEG allergy. The excipient of potential concern in the AstraZeneca COVID-19 vaccine is polysorbate 80 (PS80). Cross-reactivity between PEG and polysorbate has been suggested, based on their composition and skin-test data. The aim of this study was to determine whether PEG-allergic patients could be vaccinated with the PS80 containing AstraZeneca COVID-19 vaccine. METHOD: Eight patients with PEG allergy were identified by the allergy clinic at Cambridge University Hospital. Patients underwent skin prick testing to PS80 (20%) and to the AstraZeneca COVID-19 vaccine prior to vaccination. RESULTS: All eight patients allergic to PEG tolerated the AstraZeneca COVID-19 vaccine, even in 2 patients where the PS80 skin prick test was positive and 1 with a positive skin prick test to the AstraZeneca COVID-19 vaccine. CONCLUSION: Patients allergic to PEG, previously denied COVID vaccination, may now be safely vaccinated with the PS80 containing AstraZeneca vaccine and need only avoid the PEG-containing mRNA COVID-19 vaccines. This opens up the possibility that these patients will also tolerate other vaccines containing PS80 such as the Janssen/Johnson and Johnson COVID-19 vaccine. Clinical cross-reactivity between PEG and PS80 did not occur in this vaccine setting.