Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination.

BACKGROUND: The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms. METHODS: Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020-March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination ("controls") were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay (DCBA). Anti-PEG IgG and IgM were measured using two different assays: DCBA and a PEGylated-polystyrene bead assay. Laboratorians were blinded to case/control status. RESULTS: All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65 %) were hospitalized and 7 (35 %) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10 %) case-patients vs 8 of 30 (27 %) controls (p = 0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0 %) vs 1 of 30 (3 %) controls (p >n 0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats. CONCLUSION: Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination.

Colitis with Hypereosinophilia following the Second Dose of the BNT162b2 mRNA COVID-19 Vaccine: A Case Report with a Literature Review.

A 61-year-old man presented with a 7-day history of watery diarrhea and loss of appetite after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine. Laboratory studies showed significant eosinophilia and an elevated IgE level (white cell count, 18.4×109/L; eosinophil count, 9.5×109/L; and IgE level, 540 IU/L). Symptoms resolved 10 days after vaccination without any steroids or antiallergic medications, and the eosinophil count had also returned to within normal limits 2 months later. Several cases of eosinophilic disorders following receipt of any type of injectable COVID-19 vaccine have been reported, so the etiology should be examined.

The long-term dynamics of serum antibodies against SARS-CoV-2.

Objective: To analyze the long-term dynamics of antibodies against SARS-CoV-2 and understand the impact of age, gender, and viral load on patients' immunological response. Methods: Serum samples were obtained from 231 COVID-19 positive patients from Macaé, in Rio de Janeiro state, in Brazil, from June 2020 until January 2021. The production of IgA, IgM, IgG, and IgE against S glycoprotein was analyzed using the S-UFRJ assay, taking into account the age, gender, and viral load. Results: Analysis of antibody production over 7 months revealed that IgA positivity gradually decreased after the first month. Additionally, the highest percentage of IgM positivity occurred in the first month (97% of patients), and declined after this period, while IgG positivity remained homogeneous for all 7 months. The same analysis for IgE revealed that almost all samples were negative. The comparison of antibody production between genders showed no significant difference. Regarding the age factor and antibody production, patients aged ≥60 years produced almost twice more IgA than younger ones (17-39 years old). Finally, a relationship between viral load and antibody production was observed only for older patients. Conclusions: Our work provides an overview of long-term production of antibodies against SARS-CoV-2, suggesting prolonged production of IgA and IgM antibodies for 3 months and continued IgG production for over 7 months. In addition, it identified a correlation between viral load and IgM titers in the older group and, finally, different IgA production between the age groups.

Anti-PEG antibodies before and after a first dose of Comirnaty® (mRNA-LNP-based SARS-CoV-2 vaccine).

The early and massive vaccination campaign in Israel with the mRNA-LNP Comirnaty® (Pfizer-BioNTech) vaccine against the SARS-CoV-2 virus made available large amounts of data regarding the efficacy and safety of this vaccine. Adverse reactions to mRNA-based SARS-CoV-2 vaccines are rare events, but due to large mediatic coverage they became feared and acted as a potential source of delay for the vaccination of the Israeli population. The experience with the reactogenicity of the polyethylene glycol (PEG) moiety of PEGylated liposomes, PEGylated proteins and other PEGylated drugs raised the fear that similar adverse effects can be associated with the PEG lipid which is an essential component of currently used mRNA-LNP vaccines against COVID-19. In this study we quantified the levels of anti-PEG IgG, IgM and IgE present in the blood of 79 volunteers immediately before and 3 weeks after receiving a first dose of Comirnaty® vaccine. Our in vitro results show that different humanized anti-PEG antibodies bind the PEGylated nano-liposomes in a concentration-dependent manner, but they bind with a lower affinity to the Comirnaty vaccine, despite it having a high mole% of neutral PEG2000-lipid on its surface. We found an increase in IgG concentration in the blood 3 weeks after the first vaccine administration, but no increase in IgM or IgE. In addition, no severe signs of adverse reactions to the Comirnaty vaccine were observed in the population studied despite the significant pre-existing high titers of IgG before the first dose of vaccine in 2 donors.

HERV-W ENV antigenemia and correlation of increased anti-SARS-CoV-2 immunoglobulin levels with post-COVID-19 symptoms.

Due to the wide scope and persistence of COVID-19´s pandemic, post-COVID-19 condition represents a post-viral syndrome of unprecedented dimensions. SARS-CoV-2, in line with other infectious agents, has the capacity to activate dormant human endogenous retroviral sequences ancestrally integrated in human genomes (HERVs). This activation was shown to relate to aggravated COVID-19 patient´s symptom severity. Despite our limited understanding of how HERVs are turned off upon infection clearance, or how HERVs mediate long-term effects when their transcription remains aberrantly on, the participation of these elements in neurologic disease, such as multiple sclerosis, is already settling the basis for effective therapeutic solutions. These observations support an urgent need to identify the mechanisms that lead to HERV expression with SARS-CoV-2 infection, on the one hand, and to answer whether persistent HERV expression exists in post-COVID-19 condition, on the other. The present study shows, for the first time, that the HERV-W ENV protein can still be actively expressed long after SARS-CoV-2 infection is resolved in post-COVID-19 condition patients. Moreover, increased anti-SARS-CoV-2 immunoglobulins in post-COVID-19 condition, particularly high anti-SARS-CoV-2 immunoglobulin levels of the E isotype (IgE), seem to strongly correlate with deteriorated patient physical function (r=-0.8057, p<0.01). These results indicate that HERV-W ENV antigenemia and anti-SARS-CoV-2 IgE serology should be further studied to better characterize post-COVID-19 condition pathogenic drivers potentially differing in subsets of patients with various symptoms. They also point out that such biomarkers may serve to design therapeutic options for precision medicine in post-COVID-19 condition.

Hygienic behaviors during the COVID-19 pandemic may decrease immunoglobulin G levels: Implications for Kawasaki disease.

BACKGROUND: Due to the coronavirus disease 2019 (COVID-19) pandemic, hygienic behaviors became a new norm since January 2020. The hygiene hypothesis predicts that an excessively hygienic environment may adversely affect human health. OBJECTIVE: We quantified the effect of COVID-19 on immunological parameters linked to the hygiene hypothesis. METHODS: We examined age-specific levels of total nonspecific immunoglobulin G (IgG) and IgE in individuals who visited Fukuoka Tokushukai Hospital between 2010 and 2021. Pre-COVID (2010-2019) and COVID (2020-2021) periods were compared. RESULTS: IgG levels steadily decreased throughout Pre-COVID period. IgG levels fell abruptly from the pre-COVID period to the COVID period in all age groups (P = 0.0271, < 0.3 years; P = 0.0096, 0.3-5 years; P = 0.0074, ≥ 5 years). The declines in IgG in < 0.3 years and that in ≥ 5 years accelerated during the COVID period. IgE levels were seasonal, but did not change noticeably from the pre-COVID to COVID period. IgG levels recorded for patients with Kawasaki disease (KD) (mean 709 mg/dL) were significantly lower than for matched control subjects (826 mg/dL) (P<0.0001). DISCUSSION: Hygienic behaviors during the COVID-19 outbreak decreased the chance of infection, which may explain the decreases in IgG levels in children and adults. Neonatal IgG declined, possibly because of the decrease in maternal IgG. CONCLUSION: Hygienic behaviors decreased the IgG levels in all age groups, from neonates to adults. This downturn in IgG may lead to vulnerability to infections as well as to KD.

Edible algae (Ecklonia cava) bioprocessed with mycelia of shiitake (Lentinula edodes) mushrooms in liquid culture and its isolated fractions protect mice against allergic asthma.

BACKGROUND: Ecklonia cava is an edible marine brown alga harvested from the ocean that is widely consumed in Asian countries as a health-promoting medicinal food The objective of the present study is to evaluate the anti-asthma mechanism of a new functional food produced by bioprocessing edible algae Ecklonia cava and shiitake Lentinula edodes mushroom mycelia and isolated fractions. METHODS: We used as series of methods, including high performance liquid chromatography, gas chromatography, cell assays, and an in vivo mouse assay to evaluate the asthma-inhibitory effect of Ecklonia cava bioprocessed (fermented) with Lentinula edodes shiitake mushroom mycelium and its isolated fractions in mast cells and in orally fed mice. RESULTS: The treatments inhibited the degranulation of RBL-2H3 cells and immunoglobulin E (IgE) production, suggesting anti-asthma effects in vitro. The in vitro anti-asthma effects in cells were confirmed in mice following the induction of asthma by alumina and chicken egg ovalbumin (OVA). Oral administration of the bioprocessed Ecklonia cava and purified fractions suppressed the induction of asthma and was accompanied by the inhibition of inflammation- and immune-related substances, including eotaxin; thymic stromal lymphopoietin (TSLP); OVA-specific IgE; leukotriene C4 (LTC4); prostaglandin D2 (PGD2); and vascular cell adhesion molecule-1 (VCAM-1) in bronchoalveolar lavage fluid (BALF) and other fluids and organs. Th2 cytokines were reduced and Th1 cytokines were restored in serum, suggesting the asthma-induced inhibitory effect is regulated by the balance of the Th1/Th2 immune response. Serum levels of IL-10, a regulatory T cell (Treg) cytokine, were increased, further favoring reduced inflammation. Histology of lung tissues revealed that the treatment also reversed the thickening of the airway wall and the contraction and infiltration of bronchial and blood vessels and perialveolar inflammatory cells. The bioprocessed Ecklonia cava/mushroom mycelia new functional food showed the highest inhibition as compared with commercial algae and the fractions isolated from the bioprocessed product. CONCLUSIONS: The in vitro cell and in vivo mouse assays demonstrate the potential value of the new bioprocessed formulation as an anti-inflammatory and anti-allergic combination of natural compounds against allergic asthma and might also ameliorate allergic manifestations of foods, drugs, and viral infections.

Rational Design and Development of SARS-CoV-2 Serological Diagnostics by Immunoprecipitation-Targeted Proteomics.

Current design of serological tests utilizes conservative immunoassay approaches and is focused on fast and convenient assay development, throughput, straightforward measurements, and affordability. Limitations of common serological assays include semiquantitative measurements, cross-reactivity, lack of reference standards, and no differentiation between human immunoglobulin subclasses. In this study, we suggested that a combination of immunoaffinity enrichments with targeted proteomics would enable rational design and development of serological assays of infectious diseases, such as COVID-19. Immunoprecipitation-targeted proteomic assays allowed for sensitive and specific measurements of NCAP_SARS2 protein with a limit of detection of 313 pg/mL in serum and enabled differential quantification of anti-SARS-CoV-2 antibody isotypes (IgG, IgA, IgM, IgD, and IgE) and individual subclasses (IgG1-4 and IgA1-2) in plasma and saliva. Simultaneous evaluation of the numerous antigen-antibody subclass combinations revealed a receptor-binding domain (RBD)-IgG1 as a combination with the highest diagnostic performance. Further validation revealed that anti-RBD IgG1, IgG3, IgM, and IgA1 levels were significantly elevated in convalescent plasma, while IgG2, IgG4, and IgA2 were not informative. Anti-RBD IgG1 levels in convalescent (2138 ng/mL) vs negative (95 ng/mL) plasma revealed 385 ng/mL as a cutoff to detect COVID-19 convalescent plasma. Immunoprecipitation-targeted proteomic assays will facilitate improvement and standardization of the existing serological tests, enable rational design of novel tests, and offer tools for the comprehensive investigation of immunoglobulin subclass cooperation in immune response.

Efficacy of Liriope platyphylla extract on improving respiratory function: A CONSORT-randomized, double-blind, placebo-controlled pilot trial.

BACKGROUND: The respiratory system is the first line of defense against outside pollutants. Recently, respiratory health has been receiving increasing attention due to the increase in fine dust, which reduces respiratory function and increases incidence of chronic obstructive pulmonary disease, and in coronavirus pandemic, which can cause severe acute respiratory syndrome. METHODS: This clinical pilot trial was designed to secure evidence for a main clinical trial and to confirm the efficacy and safety of Liriope platyphylla (LP) extract for improving respiratory function. We conducted a double-blind randomized placebo-controlled trial with 22 participants from June 30, 2021, to August 25, 2021. The primary outcome was Breathlessness, Cough, and Sputum Scale score. Secondary outcomes included forced vital capacity, forced expiratory volume at 1 second (FEV1), forced expiratory volume at 1 s/forced vital capacity ratio, cough assessment test score, chronic obstructive pulmonary disease assessment test score, peripheral blood mononuclear cell counts (white blood cells, eosinophils, T cells, and B cells), high-sensitivity C-reactive protein level, erythrocyte sedimentation rate, cytokine (interleukin-1ß, interleukin-4, tumor necrosis factor-α, interleukin-6, interleukin-8, interferon-γ, and immunoglobulin E) levels, antioxidant (glutathione peroxidase and superoxide dismutase) levels, and nitric oxide level. RESULTS: A total of 22 participants were randomly assigned to 2 groups: the LP group (n = 11), who took 1000 mg of LP extract per day, and the placebo group, who took 1000 mg of dextrin per day. Participants took 1 capsule twice a day for 4 weeks. For the Breathlessness, Cough, and Sputum Scale, the interaction between group and visit was statistically significant in a blend of analyses of variance. interleukin-8, tumor necrosis factor-α, and interferon-γ levels decreased more in the LP group than in the placebo group. The sample size required for large-scale clinical trials in the future was 50. There were no side effects. CONCLUSION: LP extract can enhance respiratory function. The detailed data we obtained support conducting the future main large-scale clinical trial.

Pilot study for immunoglobulin E as a prognostic biomarker in coronavirus disease 2019.

BACKGROUND: Laboratory biomarkers to estimate the severity of coronavirus disease 2019 (COVID-19) are crucial during the pandemic since resource allocation must be carefully planned. AIMS: To evaluate the effects of basal serum total immunoglobulin E (IgE) levels and changes in inflammatory parameters on the clinical progression of patients hospitalised with COVID-19. METHODS: Patients hospitalised with confirmed COVID-19 were included in the study. Laboratory data and total IgE levels were measured on admission. Lymphocyte, eosinophil, ferritin, d-dimer and C-reactive protein parameters were recorded at baseline and on the 3rd and 14th days of hospitalisation. RESULTS: The study enrolled 202 patients, of which 102 (50.5%) were males. The average age was 50.17 ± 19.68 years. Of the COVID-19 patients, 41 (20.3%) showed clinical progression. Serum total IgE concentrations were markedly higher (172.90 (0-2124) vs 38.70 (0-912); P < 0.001) and serum eosinophil levels were significantly lower (0.015 (0-1.200) vs 0.040 (0-1.360); P = 0.002) in clinically worsened COVID-19 patients when compared with stable patients. The optimal cut-off for predicting clinical worsening was 105.2 ng/L, with 61% sensitivity, 82% specificity, 46.3% positive predictive value and 89.2% negative predictive value (area under the curve = 0.729). Multivariable analysis to define risk factors for disease progression identified higher total IgE and C-reactive protein levels as independent predictors. CONCLUSIONS: Our single-centre pilot study determined that total IgE levels may be a negative prognostic factor for clinical progression in patients hospitalised due to COVID-19 infection. Future studies are required to determine the impact of individuals' underlying immune predispositions on outcomes of COVID-19 infections.

Serum polyethylene glycol-specific IgE and IgG in patients with hypersensitivity to COVID-19 mRNA vaccines.

BACKGROUND: The mechanism of allergic reactions to COVID-19 mRNA vaccines has not been clarified. Polyethylene glycol (PEG) is a potential antigen in the components of vaccines. However, there is little evidence that allergy after COVID-19 mRNA vaccination is related to PEG. Furthermore, the role of polysorbate (PS) as an antigen has also not been clarified. The objective of this study was to investigate whether PEG and PS allergies are reasonable causes of allergic symptoms after vaccination by detecting PEG-specific and PS-specific antibodies. METHODS: Fourteen patients who developed immediate allergic reactions to BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines and nineteen healthy controls who did not present allergic symptoms were recruited. Serum PEG-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) and PS-specific IgE and IgG were measured by enzyme-linked immunosorbent assay. Skin tests using PEG-2000 and PS-80 were applied to five patients and three controls. RESULTS: Serum levels of PEG-specific IgE and IgG in patients with immediate allergic reactions to the COVID-19 mRNA vaccine were higher than those in the control group. Serum levels of PS-specific IgE in patients with allergy to the vaccine were higher than those in patients of the control group. Intradermal tests using PEG verified the results for PEG-specific IgE and IgG. CONCLUSIONS: The results suggest that PEG is one of the antigens in the allergy to COVID-19 mRNA vaccines. Cross-reactivity between PEG and PS might be crucial for allergy to the vaccines. PEG-specific IgE and IgG may be useful in diagnosing allergy to COVID-19 mRNA vaccines.

Evaluating the Performance of Inclusive Growth Based on the BP Neural Network and Machine Learning Approach.

In this paper, we use the panel data of 281 cities in China from 2005 to 2020 for capturing the factors driving urban inclusive growth (IG). In doing this, we employ the BP neural network algorithm combined with the DEA model to measure the urban inclusive growth efficiency (IGE). Furthermore, a nest of machine learning (ML) algorithms are introduced to explore the drivers of urban IGE, which overcomes the defects of endogeneity and multicollinearity of traditional econometric methods. We find for the overall sample that entrepreneurship and innovation contribute the most to IGE, accounting for about 35%, respectively, and they are the most critical drivers, while the heterogeneity test results reveal that the contribution of influencing factors has changed for different regions such as the eastern region, the central region, and the western region. Based on the experimental results of the ML model, we provide some policy suggestions for China and similar developing countries and emerging economies to promote IG.

Diversities of allergic pathologies and their modifiers: Report from the second DGAKI-JSA meeting.

In October 2021, researchers from the German Society of Allergy and Clinical Immunology (DGAKI) and from the Japanese Society of Allergology (JSA) focused their attention on the pathological conditions and modifiers of various allergic diseases. Topics included 1) the pathophysiology of IgE/mast cell-mediated allergic diseases; 2) the diagnosis and prevention of IgE/mast cell-mediated diseases; 3) the pathophysiology, diagnosis, and treatment of eosinophilic airway diseases; and 4) host-pathogen interaction and allergic diseases. This report summarizes the panel discussions, which highlighted the importance of recognizing the diversity of genetics, immunological mechanisms, and modifying factors underlying allergic diseases.

Evaluation of chlorhexidine sensitization amongst healthcare workers.

BACKGROUND: Chlorhexidine is an antiseptic widely used in healthcare settings. There are increasing reports of significant hypersensitivity reactions associated with its use. Development of chlorhexidine allergy has been identified as an important occupational risk to healthcare workers (HCWs). AIMS: To evaluate the prevalence of sensitization to chlorhexidine amongst HCWs at a large tertiary hospital to assess the potential allergic safety risks associated with chlorhexidine exposure to staff. METHODS: Sensitization to chlorhexidine was evaluated by measurement of serum-specific immunoglobulin E (IgE) in samples collected from staff assessed after a sharps-injury incident and laboratory staff collected for quality assurance procedures. This test method has been shown to have high sensitivity and specificity in the diagnosis of chlorhexidine allergy. Prevalence of sensitization was additionally evaluated with reference to changes in exposure to chlorhexidine-based hand hygiene products because of infection control procedures and the coronavirus disease 2019 pandemic. RESULTS: A total of 320 samples were examined. The prevalence of positive chlorhexidine-specific IgE was 2%. Prevalence of sensitization in samples collected before and after increased chlorhexidine exposure was 1% and 3%. This did not represent a statistically significant difference. CONCLUSIONS: The prevalence figures for chlorhexidine sensitization in this study are higher than have been estimated previously for similar HCW cohorts. Increased exposure to chlorhexidine-based hand hygiene products was not demonstrated to increase sensitization in this group. Given the risk of severe reactions in sensitized individuals, this study indicates that evaluation of chlorhexidine allergy is important when investigating occupational allergy in HCWs.

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.

Early and strong antibody responses to SARS-CoV-2 predict disease severity in COVID-19 patients.

BACKGROUND: Antibody response to SARS-CoV-2 is a valuable biomarker for the assessment of the spread of the virus in a population and evaluation of the vaccine candidates. Recent data suggest that antibody levels also may have a prognostic significance in COVID-19. Most of the serological studies so far rely on testing antibodies against spike (S) or nucleocapsid (N) protein, however antibodies can be directed against other structural and nonstructural proteins of the virus, whereas their frequency, biological and clinical significance is unknown. METHODS: A novel antigen array comprising 30 SARS-CoV-2 antigens or their fragments was developed and used to examine IgG, IgA, IgE and IgM responses to SARS-CoV-2 in sera from 103 patients with COVID-19 including 34 patients for whom sequential samples were available, and 20 pre-pandemic healthy controls. RESULTS: Antibody responses to various antigens are highly correlated and the frequencies and peak levels of antibodies are higher in patients with severe/moderate disease than in those with mild disease. This finding supports the idea that antibodies against SARS-CoV-2 may exacerbate the severity of the disease via antibody-dependent enhancement. Moreover, early IgG and IgA responses to full length S protein may be used as an additional biomarker for the identification of patients who are at risk of developing severe disease. Importantly, this is the first study reporting that SARS-CoV-2 elicits IgE responses and their serum levels positively correlate with the severity of the disease thus suggesting a link between high levels of antibodies and mast cell activation. CONCLUSIONS: This is the first study assessing the prevalence and dynamics IgG, IgA, IgE and IgM responses to multiple SARS-CoV-2 antigens simultaneously. Results provide important insights into the pathogenesis of COVID-19 and have implications in planning and interpreting antibody-based epidemiological studies.

Efficacy and safety of baked milk oral immunotherapy in children with severe milk allergy: A randomized, double-blind, placebo-controlled phase 2 trial.

BACKGROUND: Cow's milk allergy is the most common food allergy in young children and has no current treatment. Oral immunotherapy studies to date have shown efficacy but high rates of adverse reactions. OBJECTIVE: We sought to evaluate the safety and efficacy of baked milk oral immunotherapy (BMOIT) in children allergic to baked milk. METHODS: Participants (3-18 years) were randomized to receive BMOIT or placebo for 12 months. Efficacy was assessed by double-blind placebo-controlled food challenge after 12 months of treatment. Safety, quality of life, and mechanistic parameters were also evaluated. RESULTS: Eleven of 15 (73%) BMOIT participants reached the primary end point, tolerating 4044 mg of baked milk protein after 12 months of oral immunotherapy, compared with 0 of 15 (0%) on placebo. The median maximum tolerated dose and median change from baseline was significantly higher in the BMOIT group than in the placebo group (median maximum tolerated dose, 4044 mg vs 144 mg; P = .001; median change in maximum tolerated dose of 3900 mg vs 0 mg, P = .0001). Dose-related reactions were common, but more than 95% in both groups were mild. There was no significant change in cow's milk- or beta lactoglobulin-IgE from baseline for either group. Cow's milk-sIgG4 did significantly increase and casein IgE decreased in the BMOIT group. For proxy-reported food allergy quality of life, there was a significant difference in the emotional impact domain only, with more improving while on placebo compared with BMOIT. Most children and adolescents in the BMOIT group directly reported improvement in at least 1 domain. CONCLUSIONS: BMOIT was well tolerated and induced a substantial level of desensitization after 12 months of treatment.

COVID-19 vaccination in patients receiving allergen immunotherapy (AIT) or biologicals-EAACI recommendations.

Immune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen-specific manner via allergen immunotherapy (AIT) or in an endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)-5 and IL-4/IL-13 or non-type 2 response: anti-cytokine antibodies and B-cell depletion via anti-CD20. Coronavirus disease 2019 (COVID-19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.