Sub-acute hypersensitive reaction to botulinum toxin type A following Covid-19 vaccination: Case report and literature review.

RATIONALE: Botulinum toxin type A (BTA) is one of the most widely used injectable agents in cosmetic surgery. Corona virus disease 2019 (Covid-19) infection and vaccination, which can induce specific and nonspecific activation of the immune system, has been reported to induce delayed inflammatory reactions to previously injected hyaluronic acid fillers. However, there are no reports about the interaction between BTA and Covid-19. We aimed to report 2 sub-acute cases of allergic reactions to BTA in facial cosmesis following the Covid-19 vaccination. PATIENT CONCERN: A 35-year-old and a 34-year-old female who has several previous BTA injections without any adverse effects experienced facial swelling, flu-like symptoms after BTA treatment following the Covid-19 vaccination. DIAGNOSE: According to the typical clinical manifestation, a hypersensitive reaction to BTA was considered. INTERVENTION: Corticosteroids and antihistamine were administered empirically. OUTCOMES: The flu-like symptoms recovered over the next day, but the facial swelling gradually faded within 1 to 2 weeks. LESSONS: A literature review was also conducted to summarize the hypersensitive actions to cosmesis related to Covid-19. We recommend BTA injection be administered at least 2 to 3 months after Covid-19 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.

ATP/IL-33-triggered hyperactivation of mast cells results in an amplified production of pro-inflammatory cytokines and eicosanoids.

IL-33 and ATP are alarmins, which are released upon damage of cellular barriers or are actively secreted upon cell stress. Due to high-density expression of the IL-33 receptor T1/ST2 (IL-33R), and the ATP receptor P2X7, mast cells (MCs) are one of the first highly sensitive sentinels recognizing released IL-33 or ATP in damaged peripheral tissues. Whereas IL-33 induces the MyD88-dependent activation of the TAK1-IKK2-NF-κB signalling, ATP induces the Ca2+ -dependent activation of NFAT. Thereby, each signal alone only induces a moderate production of pro-inflammatory cytokines and lipid mediators (LMs). However, MCs, which simultaneously sense (co-sensing) IL-33 and ATP, display an enhanced and prolonged activation of the TAK1-IKK2-NF-κB signalling pathway. This resulted in a massive production of pro-inflammatory cytokines such as IL-2, IL-4, IL-6 and GM-CSF as well as of arachidonic acid-derived cyclooxygenase (COX)-mediated pro-inflammatory prostaglandins (PGs) and thromboxanes (TXs), hallmarks of strong MC activation. Collectively, these data show that co-sensing of ATP and IL-33 results in hyperactivation of MCs, which resembles to MC activation induced by IgE-mediated crosslinking of the FcεRI. Therefore, the IL-33/IL-33R and/or the ATP/P2X7 signalling axis are attractive targets for therapeutical intervention of diseases associated with the loss of integrity of cellular barriers such as allergic and infectious respiratory reactions.

Hypersensitivity may be involved in severe COVID-19.

BACKGROUND: Deaths attributed to Coronavirus Disease 2019 (COVID-19) are mainly due to severe hypoxemic respiratory failure. Although the inflammatory storm has been considered the main pathogenesis of severe COVID-19, hypersensitivity may be another important mechanism involved in severe cases, which have a perfect response to corticosteroids (CS). METHOD: We detected the serum level of anti-SARS-CoV-2-spike S1 protein-specific IgE (SP-IgE) and anti-SARS-CoV-2 nucleocapsid protein-specific IgE (NP-IgE) in COVID-19. Correlation of levels of specific IgE and clinical severity were analysed. Pulmonary function test and bronchial provocation test were conducted in early convalescence of COVID-19. We also obtained histological samples via endoscopy to detect the evidence of mast cell activation. RESULT: The levels of serum SP-IgE and NP-IgE were significantly higher in severe cases, and were correlated with the total lung severity scores (TLSS) and the PaO2 /FiO2 ratio. Nucleocapsid protein could be detected in both airway and intestinal tissues, which was stained positive together with activated mast cells, binded with IgE. Airway hyperresponsiveness (AHR) exists in the early convalescence of COVID-19. After the application of CS in severe COVID-19, SP-IgE and NP-IgE decreased, but maintained at a high level. CONCLUSION: Hypersensitivity may be involved in severe COVID-19.

The relationship between human coronaviruses, asthma and allergy-An unresolved dilemma.

Human coronaviruses (HCoVs) such as HCoV-229E or OC43 are responsible for mild upper airway infections, whereas highly pathogenic HCoVs, including SARS-CoV, MERS-CoV and SARS-CoV-2, often evoke acute, heavy pneumonias. They tend to induce immune responses based on interferon and host inflammatory cytokine production and promotion of T1 immune profile. Less is known about their effect on T2-type immunity. Unlike human rhinoviruses (HRV) and Respiratory Syncytial Virus (RSV), HCoVs are not considered as a dominant risk factor of severe exacerbations of asthma, mostly T2-type chronic inflammatory disease. The relationship between coronaviruses and T2-type immunity, especially in asthma and allergy, is not well understood. This review aims to summarize currently available knowledge about the relationship of HCoVs, including novel SARS-CoV-2, with asthma and allergic inflammation.

Diet Intervention Study through Telemedicine Assistance for Systemic Nickel Allergy Syndrome Patients during the COVID-19 Pandemic.

BACKGROUND: Restrictions due to the COVID-19 pandemic limited patients' access to hospital care. The aims of this study were to assess dietary nutritional status, quality of life (QoL), and adherence to dietary therapy before and after 30-day personalized diet therapy through telenutrition tools in patients with systemic nickel allergic syndrome (SNAS). METHODS: Each SNAS patient underwent the following allergological procedures: (a) face-to-face visit (nutritional visit and QoL evaluation) with prescription of one out of five personalized and balanced dietary plans different for calorie intake, (b) video call visit for dietary evaluation and assessment of adherence to diet after 15 days, and (c) video call visit for dietary and QoL evaluation and assessment of adherence to diet therapy after 30 days (end of study). RESULTS: We enrolled 20 SNAS patients. After 15 and 30 days, we found a statistically significant improvement in anthropometric findings after diet therapy, a significant adherence rate to low-nickel diet (60% and 80%, respectively), and an improvement in QoL with an increase in almost all psychometric indices. CONCLUSIONS: Our study demonstrates that telenutrition can be a valid tool to monitor nutritional status and adherence to balanced low-Ni diet positively affecting QoL in SNAS patients during the COVID-19 pandemic.

Anaphylaxis and Coronavirus Disease 2019 vaccine: a danger relationship?

PURPOSE OF REVIEW: Anaphylactic reactions reported after Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) RNA vaccines were expected to be more frequent in atopic subjects and attributed to its polyethylene glycol component. RECENT FINDINGS: Anaphylaxis to SARS-CoV2 RNA vaccines is no more frequent than in any vaccine and direct proofs for the role of its polyethylene glycol component are lacking. SUMMARY: Vaccines against coronavirus disease 2019 (COVID-19) are an essential global intervention to control the current pandemic situation. Anaphylactic reactions have rapidly been reported after SARS-CoV2 RNA vaccines. This risk is now measured at 2.5-11/1 000 000 in the context of vaccine safety surveillance programs and only one case was documented to be due to polyethylene glycol. Suggestions for its role are indirect. The COVID-19 vaccination is rolling out vastly and surveillance programs are key to monitor severe adverse reactions, such as anaphylaxis. Anaphylaxis due to vaccine is extremely rare and specific cases should receive individualized investigation and care, highlighting the key role of allergists in the vaccination programmes.

Primary care provider-reported prevalence of vaccine and polyethylene glycol allergy in Canada.

BACKGROUND: The coronavirus disease 2019 pandemic has highlighted the importance of accurate capture of vaccine, and vaccine component, allergy. There remains a gap in the prevalence literature from the perspective of direct primary care provider (PCP) reporting at a population level. OBJECTIVE: To determine the prevalence of PCP-documented vaccine and polyethylene glycol (PEG) allergy using electronic medical record data from the Canadian Primary Care Sentinel Surveillance Network. METHODS: Retrospective cohort study using the Canadian Primary Care Sentinel Surveillance Network repository. Machine learning algorithms were applied to evaluate for vaccine allergy documentation, and Anatomic Therapeutic Chemical codes were used for PEG allergy or allergy to common injectable medications containing PEG (CIMCP). RESULTS: The prevalence of PCP-documented vaccine allergy in Canada was 0.037% (395/1,055,677) and of PEG allergy was 0.0009% (10/1,055,677). In total, 0.01% of patients had a documented allergy to either PEG or CIMCP (135/1,055,677). None of the patients with PEG allergy had a documented allergy to a CIMCP. Patients with vaccine allergy and PEG allergy were significantly more likely to have other atopic comorbidities, including asthma (P < .001 for both), eczema (P < .001 and P = .001, respectively), rhinitis (P = .002 and P < .001, respectively), and food allergy (P < .001 for both). Significantly higher rates of depression (P < .001 and P < .001, respectively) and anxiety (P = .003 and P < .001, respectively) were found in those with vaccine allergy, or PEG allergy, than those without vaccine allergy or PEG allergy. CONCLUSION: This is the first study to estimate the prevalence of vaccine and PEG allergy in a national cohort that uses PCP documentation, revealing a low reported rate of vaccine allergy and PEG allergy.

Coronavirus disease 2019, allergic diseases, and allergen immunotherapy: Possible favorable mechanisms of interaction.

Background: Both, allergen immunotherapy (AIT) and SARS-COV-2 infection cause a set of immunologic changes that respectively vary during the course of the treatment or the disease. Objective: To review immune changes brought along by each of these entities and how they might interrelate. Methods: We start presenting a brief review of the structure of the new coronavirus and how it alters the functioning of the human immune system. Subsequently, we describe the immune changes induced by AIT and how these changes could be favorable or unfavorable in the allergic patient infected with SARS-CoV-2 at a particular point of time during the evolving infection. Results: We describe how a healthy immune response against SARS-CoV-2 develops, versus an immune response that is initially suppressed by the virus, but ultimately overactivated, leading to an excessive production of cytokines (cytokine-storm-like). These changes are then linked to the clinical manifestations and outcomes of the patient. Reviewing the immune changes secondary to AIT, it becomes clear how AIT is capable of restoring a healthy innate immunity. Investigators have previously shown that the frequency of respiratory infections is reduced in allergic patients treated with AIT. On the other hand it also increases immunoregulation. Conclusion: As there are many variables involved, it is hard to predict how AIT could influence the allergic patient's reaction to a SARS-CoV-2 infection. In any case, AIT is likely to be beneficial for the patient with allergic rhinitis and/or allergic asthma in the context of the SARS-CoV-2 pandemic as controlling allergic diseases leads to a reduced need for contact with healthcare professionals. The authors remind the reader that everything in this article is still theoretical, since at the moment, there are no published clinical trials on the outcome of COVID-19 in allergic patients under AIT.

Insights into allergic risk factors from birth cohort studies.

OBJECTIVE: To present an update of birth cohort study designs and their contributions to allergic risk. DATA SOURCES: The PubMed database was used to search for relevant articles. STUDY SELECTIONS: Peer-reviewed prospective and retrospective studies involving the assessment of allergy using human birth cohorts between 2014 and 2021 were evaluated. RESULTS: Parental history of allergic diseases, especially in cases involving both parents, is associated with increased risk of allergy. Exposure to prenatal and postnatal smoking and limited diet diversity were associated with increased allergic burden. The impact of early-life infections and antibiotics on disease development may be associated with the onset of asthma, though this remains debated. Cohort studies also revealed that the mode of delivery and breastfeeding duration affect the odds ratio of asthma and eczema development. Household exposures, including pets, house dust mites, and scented aeroallergens may confer protective effects, whereas high air pollution exposure and low socioeconomic status may be risk enhancing. Exposure to antibiotics during early life may be associated with increased asthma risk, whereas viral infections may lead to disease protection, though the impact of the coronavirus disease 2019 pandemic on allergic risk is yet to be understood. CONCLUSION: Although evaluating the risk of allergic disease development is complex, clinicians can apply these insights on the multifactorial nature of atopy to better understand and potentially mitigate disease development.

The microbiome in atopic patients and potential modifications in the context of the severe acute respiratory syndrome coronavirus 2 pandemic.

PURPOSE OF REVIEW: Data regarding the effects of coronavirus disease 2019 (COVID-19) on host-microbiome alteration and subsequent effects on susceptibility and clinical course of COVID-19, especially in atopic patients, are currently limited. Here, we review the studies regarding the microbiome of atopic patients with other respiratory infections and discuss the potential role of probiotics as therapeutic targets for COVID-19 to decrease its susceptibility and severity of COVID-19. RECENT FINDINGS: Respiratory tract virus infection affects the gut and airway microbiome structures and host's immune function. Diverse factors in atopic diseases affect the airway and gut microbiome structures, which are expected to negatively influence host health. However, response to respiratory virus infection in atopic hosts depends on the preexisting microbiome and immune responses. This may explain the inconclusiveness of the effects of COVID-19 on the susceptibility, morbidity, and mortality of patients with atopic diseases. Beneficial probiotics may be a therapeutic adjuvant in COVID-19 infection as the beneficial microbiome can decrease the viral load in the early phase of respiratory virus infection and improve the morbidity and mortality. SUMMARY: Application of probiotics can be a potential adjuvant treatment in respiratory virus infection to improve host immune responses and disturbed microbiome structures in atopic patients. Further related studies involving COVID-19 are warranted in near future.

Bacille Calmette Guérin (BCG) and new TB vaccines: Specific, cross-mycobacterial and off-target effects.

The Bacille Calmette Guérin (BCG) vaccine was developed over a century ago and has become one of the most used vaccines without undergoing a modern vaccine development life cycle. Despite this, the vaccine has protected many millions from severe and disseminated forms of tuberculosis (TB). In addition, BCG has cross-mycobacterial effects against non-tuberculous mycobacteria and off-target (also called non-specific or heterologous) effects against other infections and diseases. More recently, BCG's effects on innate immunity suggest it might improve the immune response against viral respiratory infections including SARS-CoV-2. New TB vaccines, developed over the last 30 years, show promise, particularly in prevention of progression to disease from TB infection in young adults. The role of BCG in the context of new TB vaccines remains uncertain as most participants included in trials have been previously BCG immunised. BCG replacement vaccines are in efficacy trials and these may also have off-target effects.

JAK1 Inhibition Blocks Lethal Immune Hypersensitivity in a Mouse Model of Down Syndrome.

Individuals with Down syndrome (DS; trisomy 21) display hyperactivation of interferon (IFN) signaling and chronic inflammation, which could potentially be explained by the extra copy of four IFN receptor (IFNR) genes encoded on chromosome 21. However, the clinical effects of IFN hyperactivity in DS remain undefined. Here, we report that a commonly used mouse model of DS overexpresses IFNR genes and shows hypersensitivity to IFN ligands in diverse immune cell types. When treated repeatedly with a TLR3 agonist to induce chronic inflammation, these animals overexpress key IFN-stimulated genes, induce cytokine production, exhibit liver pathology, and undergo rapid weight loss. Importantly, the lethal immune hypersensitivity and cytokine production and the ensuing pathology are ameliorated by JAK1 inhibition. These results indicate that individuals with DS may experience harmful hyperinflammation upon IFN-inducing immune stimuli, as observed during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, pointing to JAK1 inhibition as a strategy to restore immune homeostasis in DS.

Recent Advances in the Use of Plant Virus-Like Particles as Vaccines.

Vaccination is one of the most effective public health interventions of the 20th century. All vaccines can be classified into different types, such as vaccines against infectious diseases, anticancer vaccines and vaccines against autoimmune diseases. In recent decades, recombinant technologies have enabled the design of experimental vaccines against a wide range of diseases using plant viruses and virus-like particles as central elements to stimulate protective and long-lasting immune responses. The analysis of recent publications shows that at least 97 experimental vaccines have been constructed based on plant viruses, including 71 vaccines against infectious agents, 16 anticancer vaccines and 10 therapeutic vaccines against autoimmune disorders. Several plant viruses have already been used for the development of vaccine platforms and have been tested in human and veterinary studies, suggesting that plant virus-based vaccines will be introduced into clinical and veterinary practice in the near future.