Longitudinal Alpha-gal IgE Levels in a University of Virginia Employee Cohort

Rationale: The alpha-gal syndrome (AGS) is caused by IgE to galactose-α-1,3-galactose (α-Gal) and is strongly linked to tick bites. To date there have been limited studies on the natural history of AGS and α-Gal sensitization. Here we monitored α-Gal IgE levels over time among sensitized individuals in an employee vaccine cohort unselected for allergic disease. Methods: University of Virginia employees were recruited for an IRB-approved COVID-19 vaccine study. Study subjects provided blood samples and answered a questionnaire capturing medical history including diet and allergy history. α-Gal IgE (cut-off 0.1 kU/L) and total IgE were assayed in banked serum by ImmunoCAP and slopes calculated by linear regression. Results: Of the 266 subjects in the study, 46 (17%) were sensitized to alpha-gal. 38 sensitized subjects had two or more samples separated by at least 100 days. Of these, 68% were female, median age was 55.6 and α-Gal IgE levels dropped over time in 25 (66%). Median rate of decay among subjects with decreasing titers was 53%/year (IQR 46-61). Of the 38 sensitized subjects, 12 (32%) reported interval tick bites over the course of the study. The correlation between α-Gal IgE slopes and total IgE slopes was moderately strong (Pearson's R = 0.60, P<0.001). Conclusions: α-Gal IgE levels decrease over time in many subjects, with a median decay rate of 53%/year. Although α-Gal specific IgE is often only a small fraction of total IgE, both track closely with each other over time, likely a reflection of changes in IgE relating to tick bites.

Virtual Healthcare Is Everywhere, But Are Caregivers Satisfied With Virtual Learning And Does It Have A Role Moving Forward?

Rationale: Covid-19 introduced a shift towards telemedicine in paediatric healthcare. In-person education opportunities were therefore reduced. Virtual education opportunities are developing, but do caregivers want these permanently? This study assesses caregivers' experiences following an online anaphylaxis education session. Methods: This project uses data collected as part of the ongoing TEAAM study (Telemedicine as an Educational tool for caregivers regarding Auto-Injectors and Anaphylaxis Management). TEAAM examines the efficacy of online education in improving caregiver anaphylaxis knowledge using a virtual session (with a trainer and video resources), and pre- and post- intervention surveys. The TEAAM population consists of a convenience sample of caregivers of children attending allergy clinic, who have a food allergy and have been prescribed adrenaline. 65 caregivers have completed a post-intervention questionnaire in which we assessed their satisfaction level, perceived benefits, issues and comparison to in-person education. Results: 98.5%(64) of caregivers found participation beneficial (mean satisfaction score 4.7/5). Benefits included time saved (n=55,84.6%), and money saved (n=33,50.8%) due to less travel, having access to education while awaiting appointments (n=54,83.1%), and reduced exposure to infection (n=28,43.1%). During sessions, 78.5%(50) expressed no issues. 3.1%(2) had issues logging in. 9.2%(6) mentioned trainer difficulties in sharing screens. Qualitative comments showed confidence in online education platforms e.g., "I definitely think sessions like this are the way forward”. Only 1 caregiver believed it would be more useful if delivered in-person. Conclusions: Caregivers found online allergy education sessions worthwhile and would like them to continue. Moving forward, we need to build user-friendly, distance-learning resources and ensure staff are adequately trained.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.

Normative Data for the Impairment Measure for Parental Food Allergy-Associated Anxiety and Coping Tool (IMPAACT) in a Canadian Sample

Rationale: The Impairment Measure for Parental Food Allergy-Associated Anxiety and Coping Tool (IMPAACT) is a food-allergy anxiety questionnaire for parents of children with food allergy. While the measure has been recently validated, normative data has not yet been presented. As such, the current study provides preliminary cut-scores and percentiles to help facilitate its use as a screening tool. Methods: Parents of children with food allergy were largely recruited through national and local patient organizations and were asked to complete questionnaires aimed at assessing their demographics and IMPAACT scores pre/post COVID-19. While the data was primarily analyzed descriptively (n/N, %, mean, SD, percentiles), inferential statistics were used to assess the relationship between the IMPAACT and various participant characteristics. Results: The final sample consisted of 281 parents (mothers=92%) and ranged in age from 27-64 years. The majority of participants reported having one child with a food allergy (85%). Allergies to peanuts were most common (79%), followed by tree nuts (56%), eggs (33%), and cow's milk (24%). IMPAACT scores were significantly lower following the outbreak of COVID-19 relative to the period prior to the outbreak (mean 87.89 [SD=36.44] vs. 102.97 [SD=33.71], p<0.001;maximum possible score: 196). Given these differences in food allergy anxiety before and after the pandemic, percentiles and cut-scores for both periods are presented. IMPAACT scores greater than 125, or 112 during periods of public health restrictions/reduced socialization, may merit further evaluation. Conclusions: Findings provide preliminary cut-points and percentiles that may help identify parents with elevated levels of food allergy anxiety.

Comparison Of The Efficacy And Safety Of Secukinumab, Ustekinumab And Guselkumab For The Treatment Of Moderate To Severe Plaque Psoriasis: A Systematic Review

Psoriasis is a chronic inflammatory skin condition characterized by scaly erythematous patches or plaques affecting the extensor surfaces that are prominent but spreading to all areas of the body, including the flexor surfaces. Psoriasis occurs when the body's immune system attacks the skin;the interleukin (IL)-12 and IL-17/23 axes play a major role in its pathogenesis. Biologic therapies targeting IL-17 or IL-23 have emerged as an important treatment option for psoriasis and have led to substantial improvements in patients' quality of life. This systematic review aimed to evaluate the comparative efficacy and safety of secukinumab, ustekinumab and guselkumab for the treatment of moderate to severe plaque psoriasis. Based on the final analysis, there were 10 articles, namely 5 RCTs and 5 observational. We found that patients who were given secukinumab showed a rapid response, whereas guselkumab was superior in terms of long-term response (approximately 1 year) and complete remission compared to other biologics. Among all the biologics assessed, ustekinumab showed relatively low efficacy.

What do patients with asthma want to know? Google Trends insights into U.S. general population interest between 2004 and 2022 can help structure patient education initiatives

Rationale: The aim of this study is to use the research tool Google Trends to analyze U.S. general population interest in asthma. Methods: The research tool Google Trends (trends.google.com) was used to access data sets for the searched term "asthma” between 2004 and 2022 (English language, U.S. location). Data were normalized and adjusted to make comparisons between search terms substantiated. Each data point was divided by the total searches of the geography and time range it represented. Results: Searches for asthma detected have remained stable in terms of volume between 2004 and 2022 apart from a spike during February-May 2020 which corresponded with one of the peaks of the COVID pandemic. Top 5 states for asthma searches in 2022 were Kentucky, Tennessee, Connecticut, Mississippi, Maryland. The list of the top states is dynamic and has changed since 2004.Top search terms in the U.S. in 2022 were: allergy, allergy asthma, asthma and allergy, asthma symptoms, asthma attack. Searches for allergy have consistently been present in the top 5 terms when patients searched for asthma during the last 18 years, between 2004 and 2022. Conclusions: Asthma-related Google searches reveal topics of high interest that could supplement the understanding about general population interest. Searches for allergy have consistently been present in the top 5 terms when patients searched for asthma during the last 18 years, emphasizing the role of allergists/immunologists in asthma care. Knowledge of variability in search patterns and specific topics could help allergy organizations and practicing allergists focus their educational programs towards patients' interests.

Rates of New Peanut Allergy and Discontinuation Following Introduction in High-Risk Infants

Rationale: Current guidelines recommend peanut introduction to high-risk infants. However, compliance and rates of new peanut allergy (PA) require further study. Methods: Participants aged 4-11 months with no prior peanut exposure and (i) diagnosis of non-peanut food allergy, (ii) moderate-severe atopic dermatitis, or (iii) first degree relative with PA were enrolled. PA status was determined by skin testing and food challenge. Participants without PA were advised to consume 2 grams of peanut protein three times/week. Monthly questionnaires were administered, with follow-up visits at 18 and 30 months. Results: At baseline, 35/326 (11%) participants were peanut allergic. Of 291 without PA, 78 (27%) discontinued peanut at least temporarily 115 times during follow-up because of suspected participant reaction (40%), fear of reaction (3%), reaction or fear of reaction in a family member (21%), participant refusal (9%), peanut introduction was too much work (3%), or other reasons (23%), including the COVID-19 pandemic. Six of 291 participants (2.1%) who consumed peanut developed PA (2 consistent with FPIES). Among 291 participants without PA at baseline, none of the 17 participants with initial skin prick test of at least 4 mm and <10 mm developed PA. Conclusions: New PA after early introduction recommendations was rare, confirming the LEAP study findings. Transient discontinuation was common, mostly due to suspected participant reaction. High-risk children may require substantial support to keep peanut in their diet.

Examining virtual research recruitment and participant diversity in a multi-center birth cohort, Childhood Allergy and the NeOnatal Environment" (CANOE)

Rationale: Recruitment for a NIH/ECHO-supported multi-center birth cohort, "Childhood Allergy and the NeOnatal Environment” (CANOE) stopped due to the COVID-19 pandemic. Redesign of study procedures emphasized virtual and socially distanced activities. We hypothesized that "virtual” recruitment methods (social media, websites, email) would surpass "traditional” methods (in-clinic, telephone, flyers/print materials) and increase enrollment of families from diverse backgrounds and communities. Methods: Pregnant women (n=439, target 500) were recruited from four academic medical centers in Detroit MI, Madison WI, Nashville TN, and St. Louis MO. We collected demographic and social information by questionnaires and examined race, ethnicity, age, parity, and employment status in relation to recruitment method using chi-square tests. Results: In-clinic and telephone recruitment comprised 55% of enrollment, followed by print materials (17%), and social media and email (15%). The cohort includes families self-identifying as Caucasian/White (63%), African American/Black (27%), Hispanic/Latino (3.3%), Asian (3.5%), and mixed races (1.2%). This reflects site demographics for White and Black patients, while other populations are not as well recruited into this cohort. Recruitment method success did not vary by race, ethnicity, maternal age, or employment status (p=ns for each comparison). Most (63%) multigravida mothers (9.1% of participants) were recruited in clinic, while primigravida participants were recruited more evenly via all methods. Conclusions: "Virtual” recruitment methods comprised a smaller proportion of cohort enrollment than hypothesized and study recruitment method did not vary by race/ethnicity;however, consideration of combined, varied, and novel recruitment methods may add to the development of best practices for more representative research study recruitment.

Food Insecurity and Food Allergy in Children of an Urban Minority Community: A Cross-Sectional Study

Rationale: Childhood food insecurity was exacerbated during the COVID-19 pandemic, with burdens falling disproportionately on minority children. This study aims to describe the prevalence of food insecurity in food-allergic children of an urban minority community and examine the association between food insecurity and food allergy. Methods: We conducted a retrospective review of electronic medical records of all patients aged 6 months to 18 years seen in a primary care pediatric clinic at NYC Health + Hospitals/Kings County, from 10/2020 to 06/2022. Pediatricians at this clinic in Central Brooklyn routinely screen for food insecurity using the Hunger Vital Sign™, a validated tool recommended by the American Academy of Pediatrics. Data was collected based on ICD-10 diagnosis codes for food insecurity (Z59.41) and food allergy (Z91.01). Logistic regression was used for analysis. Results: Among 7,856 children included in the study, 84.9% were Black or African American, 6.0% Hispanic/Latinx, 1.2% white, and 1.1% were Asian/Pacific Islander. Of 275 children diagnosed with a food allergy by a primary care pediatrician, 4.7% screened positive for food insecurity. Of 7,581 children without a diagnosed food allergy, 2.6% screened positive for food insecurity (p=0.029). Children with food allergy (adjusted odds ratio: 2.14, 95% confidence interval: 1.19-3.85) were significantly more likely to be food insecure than those without a food allergy, adjusted for age, gender, and race/ethnicity. Conclusions: Childhood food allergy is associated with increased odds of food insecurity. This study highlights the importance of assessing and addressing food insecurity in children with food allergies.

Asthma Management Among Children With Food Allergy in the FORWARD Study During COVID-19

Rationale: Asthma remains a significant comorbidity among children with food allergy (FA). Longitudinal data on the course of asthma in this population, particularly during the COVID-19 pandemic, is lacking. This study aims to describe asthma management and control among children with FA during the COVID-19 pandemic. Methods: Children with FA (≤12 years old at enrollment) were enrolled into FORWARD, a prospective, observational cohort study. Data from participants with FA and asthma who completed a 12-month and 24-month post-enrollment asthma therapy assessment were included (n=125). Surveys were administered between January 2019 - July 2022, which includes the onset and duration of COVID-19. Responses to the same questions at the two time points were analyzed using tests of exact symmetry. Results: Compared to the 12-month survey, caregivers at the 24-month survey more frequently reported that their children were not using their inhaler for quick relief (1.6% vs. 9.4%, p = 0.008) and were using their medication incorrectly (3.2% vs. 8.7%, p = 0.003). They less frequently reported that they were unsure whether their medications were useful (3.2% vs. 0.0%, p = 0.016). A similar distribution was observed when non-Hispanic Black and non-Hispanic White participants were compared. No significant differences were evident when comparing symptoms. Conclusions: The symptom burden of asthma remained stable even during the pandemic. However, during this time, children with asthma were less likely to need a rescue inhaler and to be adherent to their maintenance regimen. Further longitudinal research on asthma management is necessary to better understand the potential impact of COVID-19.

Self-Reported Allergic Adverse Events Following Inactivated SARS-CoV-2 Vaccine (TURKOVAC™) among General and High-Risk Population.

TURKOVAC™ is a whole-virion inactivated COVID-19 vaccine which was developed and granted emergency use and conditional marketing authorization in December 2021 in Türkiye. The objective of this study is to assess the distribution and the severity of allergic adverse events following the administration of the vaccine as the primary or the booster dose in 15 provinces in Türkiye. In this cohort study, between February and May 2022, in the selected 15 provinces having an adequate number of health care personnel in the community health centers to conduct the study, 32,300 people having the first, the second, or the booster dose of the vaccine were invited to the survey. A total of 29,584 people voluntarily agreed to participate to the survey and were given a structured questionnaire after a minimum of 10 days following the vaccination. In our study, only 0.5% of the participants (142 persons) reported to experience any allergic reaction, and 12 of them (8.5%) reported to be given medical treatment in a health center. Male predominance (55.6%) was observed among participants reported to experience any allergic reaction. No hospitalization was recorded. Of the participants, 4.4% (1315 people) reported to have a history of allergy. The most reported allergens were drugs. Among the participants without a known history of allergy (n = 28,269), 0.4% of them (110 people) reported to experience an allergic reaction following the vaccination, and 5.4% of the allergic reactions (six people) were reported to be treated in a health center. The percentage of the participants given any medical treatment among the participants without a known history of allergy is 0.02%. No immediate or anaphylactic reaction was reported. Among the participants with a known history of allergy (n = 1315), 32 people (2.4% of them) reported to experience an allergic reaction following the vaccination, and 18.7% of the allergic reactions (six people) were reported to be prescribed a medical treatment. The percentage of the participants given any medical treatment among the participants with a known history of allergy is 0.4%. A known history of allergy increased the risk of having an allergic experience by approximately six times following vaccination. As a whole-virion inactivated SARS-CoV-2 vaccine, the TURKOVAC™ vaccine, with a low allergic reaction-related adverse event profile, can be an alternative to other COVID-19 vaccines.

Is antenatal or early-life vitamin D associated with eczema or food allergy in childhood? A systematic review.

OBJECTIVE: To summarise the associations between antenatal or early-life blood vitamin D and the development of eczema/food allergy in childhood. DESIGN: A systematic review and meta-analyses were conducted to synthesize the published literature. Two reviewers independently performed the study selection and data extraction on Covidence. We assessed the risk of bias for observational studies by using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool for clinical trials. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). DATA SOURCES: We systematically searched PubMed and Embase from inception and April 2022. ELIGIBILITY CRITERIA: Human studies that investigated prospective associations between antenatal or early-life blood vitamin D levels, dietary intake or supplementation and childhood eczema/food allergy. RESULTS: Forty-three articles including six randomised controlled trials (RCTs) were included. Four RCTs of vitamin D supplementation during pregnancy showed no evidence of an effect on the incidence of eczema (pooled odds ratio [OR] = 0.85; 0.67-1.08, I2  = 6.7%, n = 2074). Three RCTs reported null associations between supplementation in pregnancy/infancy and food allergy. From six cohort studies, increasing cord blood vitamin D levels were associated with reduced prevalence of eczema at/close to age one (OR per 10 nmol/L increase = 0.89; 0.84-0.94, I2  = 0%, 2025 participants). We found no evidence of an association between maternal antenatal or infant vitamin D level or dietary intake and the development of food allergy or eczema in offspring. CONCLUSIONS: We found an association between higher vitamin D levels in cord blood and reduced risk of eczema in cohort studies. Further trials with maternal and infant supplementation are needed to confirm if vitamin D supplementation can effectively prevent eczema or food allergy in childhood. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, No. CRD42013005559.

New considerations of health disparities within allergy and immunology.

The pandemic, political upheavals, and social justice efforts in our society have resulted in attention to persistent health disparities and the urgent need to address them. Using a scoping review, we describe published updates to address disparities and targets for interventions to improve gaps in care within allergy and immunology. These disparities-related studies provide a broad view of our current understanding of how social determinants of health threaten patient outcomes and our ability to advance health equity efforts in our field. We outline next steps to improve access to care and advance health equity for patients with allergic/immunologic diseases through actions taken at the individual, community, and policy levels, which could be applied outside of our field. Key among these are efforts to increase the diversity among our trainees, providers, and scientific teams and enhancing efforts to participate in advocacy work and public health interventions. Addressing health disparities requires advancing our understanding of the interplay between social and structural barriers to care and enacting the needed interventions in various key areas to effect change.

Time course of adverse reactions following BNT162b2 vaccination in healthy and allergic disease individuals aged 5-11 years and comparison with individuals aged 12-15 years: an observational and historical cohort study.

We aimed to investigate the type and frequency of adverse events over 7 days following the first and second BNT162b2 vaccination. This observational and historical cohort study included patients aged 5-11 years who received two doses of BNT162b2 and provided consent along with their guardians. We collected data on sex, age, height, weight, blood type, history of Bacille Calmette-Guerin vaccination, allergic disease, medication, history of coronavirus disease 2019 (COVID-19), and adverse reactions 7 days following the first and second BNT162b2 vaccination using a questionnaire. Our results were compared with previously reported results for individuals aged 12-15 years. A total of 421 participants were eligible for this study. Among the 216 patients with allergic disease, 48 (22.2%) had experienced worsening of their chronic diseases, and the frequency of fatigue and dizziness after the second dose was higher than that of healthy individuals. The experience of systemic adverse reactions was associated with asthma. The frequency of headache, diarrhea, fatigue, muscle/joint pain, and fever after the second BNT162b2 vaccination was lower in individuals aged 5-11 years than in those aged 12-15 years. Fever was the only systemic adverse reaction that lasted longer than 5 days (1.0% of participants). CONCLUSIONS: Individuals with allergic diseases, who are potentially susceptible to COVID-19, may experience worsening of their chronic diseases and more frequent adverse reactions after BNT162b2 vaccination than healthy individuals. To ensure that children with allergic diseases receive the vaccine safely, further information needs to be collected. WHAT IS KNOWN: • Adverse reactions after BNT162b2 vaccination among individuals aged 5-11 years are generally nonserious, more common after second vaccination, and substantially less common compared to those observed among individuals aged 12-15 years. WHAT IS NEW: • Individuals with allergic diseases experienced worsening of their chronic diseases and more frequent adverse reactions after BNT162b2 vaccination than healthy individuals. • Systemic adverse reactions were associated with asthma. Fever was the only systemic adverse reaction that lasted longer than 5 days.

Viral infections and drug hypersensitivity.

Virus infections and T-cell-mediated drug hypersensitivity reactions (DHR) can influence each other. In most instances, systemic virus infections appear first. They may prime the reactivity to drugs in two ways: First, by virus-induced second signals: certain drugs like ß-lactam antibiotics are haptens and covalently bind to various soluble and tissue proteins, thereby forming novel antigens. Under homeostatic conditions, these neo-antigens do not induce an immune reaction, probably because co-stimulation is missing. During a virus infection, the hapten-modified peptides are presented in an immune-stimulatory environment with co-stimulation. A drug-specific immune reaction may develop and manifest as exanthema. Second, by increased pharmacological interactions with immune receptors (p-i): drugs tend to bind to proteins and may even bind to immune receptors. Without viral infections, this low affine binding may be insufficient to elicit T-cell activation. During a viral infection, immune receptors are more abundantly expressed and allow more interactions to occur. This increases the overall avidity of p-i reactions and may even be sufficient for T-cell activation and symptoms. There is a situation where the virus-DHR sequence of events is inversed: in drug reaction with eosinophilia and systemic symptoms (DRESS), a severe DHR can precede reactivation and viremia of various herpes viruses. One could explain this phenomenon by the massive p-i mediated immune stimulation during acute DRESS, which coincidentally activates many herpes virus-specific T cells. Through p-i stimulation, they develop a cytotoxic activity by killing herpes peptide-expressing cells and releasing herpes viruses. These concepts could explain the often transient nature of DHR occurring during viral infections and the often asymptomatic herpes-virus viraemia after DRESS.

Allergy Workup in the Diagnosis of COVID-19 Vaccines-Induced Hypersensitivity Reactions and Its Impact on Vaccination.

INTRODUCTION: Immediate and delayed hypersensitivity reactions (HSR) to COVID-19 vaccines are rare adverse events that need to be prevented, diagnosed, and managed in order to guarantee adherence to the vaccination campaign. The aims of our study were to stratify the risk of HSR to COVID-19 vaccines and propose alternative strategies to complete the vaccination. METHODS: 1,640 subjects were screened for vaccinal eligibility, according to national and international recommendations. Among them, we enrolled for allergy workup 152 subjects, 43 with HSR to COVID-19 vaccines and 109 at high risk of HSR to the first dose. In vivo skin tests with drugs and/or vaccines containing PEG/polysorbates were performed in all of them, using skin prick test and, when negative, intradermal tests. In a subgroup of patients resulted negative to the in vivo skin tests, the programmed dose of COVID-19 vaccine (Pfizer/BioNTech) was administered in graded doses regimen, and detection of neutralizing anti-spike antibodies was performed in these patients after 4 weeks from the vaccination, using the SPIA method. RESULTS: Skin tests for PEG/polysorbates resulted positive in only 3% (5/152) of patients, including 2 with previous HSR to COVID-19 vaccines and 3 at high risk of HSR to the first dose. Among the 147 patients with negative skin tests, 97% (143/147) were eligible for vaccination and 87% (124/143) of them received safely the programmed COVID-19 vaccine dose. Administration of graded doses of Pfizer/BioNTech vaccine were well tolerated in 17 out of 18 patients evaluated; only 1 developed an HSR during the vaccination, less severe than the previous one, and all developed neutralizing anti-spike antibodies after 4 weeks with values comparable to those subjects who received the vaccine in unfractionated dose. CONCLUSION: On the whole, the usefulness of the skin tests for PEG/polysorbates seems limited in the diagnosis of HSR to COVID-19 vaccines. Graded doses regimen (Pfizer/BioNTech) is a safe and effective alternative strategy to complete the vaccinal course.