Updated guidance regarding the risk of allergic reactions to COVID-19 vaccines and recommended evaluation and management: A GRADE assessment and international consensus approach.

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.

Allergic reactions to the coronavirus disease 2019 vaccine (ARCOV) study: The McGill University Health Centre experience.

BACKGROUND: Messenger RNA coronavirus disease 2019 (COVID-19) vaccines have been associated with allergic reactions. A history of anaphylaxis has been suggested as a risk factor for such reactions. Polyethylene glycol (PEG) has been proposed as a possible culprit allergen. OBJECTIVE: To investigate possible PEG or polysorbate allergy among patients reporting prior reactions to COVID-19 vaccines or PEG and to report their subsequent tolerance of COVID-19 vaccines. METHODS: From January 1, 2021, to October 31, 2021, adult patients referred to the McGill University Health Centre allergy clinics who were considered at risk of anaphylaxis were prospectively recruited. The entry criteria were any documented history of reaction to a COVID-19 vaccine or reported allergy to PEG or polysorbate. Evaluated patients underwent skin prick testing (SPT) with PEG and polysorbate. After SPT, placebo-controlled vaccine challenges were carried out. RESULTS: Of the 44 patients recruited, 40 (90.1%) had reacted to the first vaccine dose, with 18 (45%) of them had anaphylactic reaction. All patients underwent SPT and 5 (11.3%) had a positive test result. A total of 39 patients (88.6%) underwent COVID-19 vaccine challenge at the allergy clinic. Most tolerated the vaccine, with 18 (40.1%) received a single full dose, 20 (45.4%) 2 split doses, and 6 (13.6%) a graded dosing protocol. Of the 40 patients who reacted to the first dose, 2 had immediate nonsevere allergic reactions to the second dose. CONCLUSION: In this cohort of patients with a history of anaphylaxis and increased risk of allergic reactions to the COVID-19 vaccines, after allergist evaluation, including negative PEG skin testing result, the vaccine was safely administered without any serious adverse events.

Immunodeficiency and EBV-induced lymphoproliferation caused by 4-1BB deficiency.

BACKGROUND: The tumor TNF receptor family member 4-1BB (CD137) is encoded by TNFRSF9 and expressed on activated T cells. 4-1BB provides a costimulatory signal that enhances CD8+ T-cell survival, cytotoxicity, and mitochondrial activity, thereby promoting immunity against viruses and tumors. The ligand for 4-1BB is expressed on antigen-presenting cells and EBV-transformed B cells. OBJECTIVE: We investigated the genetic basis of recurrent sinopulmonary infections, persistent EBV viremia, and EBV-induced lymphoproliferation in 2 unrelated patients. METHODS: Whole-exome sequencing, immunoblotting, immunophenotyping, and in vitro assays of lymphocyte and mitochondrial function were performed. RESULTS: The 2 patients shared a homozygous G109S missense mutation in 4-1BB that abolished protein expression and ligand binding. The patients' CD8+ T cells had reduced proliferation, impaired expression of IFN-γ and perforin, and diminished cytotoxicity against allogeneic and HLA-matched EBV-B cells. Mitochondrial biogenesis, membrane potential, and function were significantly reduced in the patients' activated T cells. An inhibitory antibody against 4-1BB recapitulated the patients' defective CD8+ T-cell activation and cytotoxicity against EBV-infected B cells in vitro. CONCLUSION: This novel immunodeficiency demonstrates the critical role of 4-1BB costimulation in host immunity against EBV infection.

Premedication Protocols to Prevent Hypersensitivity Reactions to Chemotherapy: a Literature Review.

Hypersensitivity reactions (HSRs) to chemotherapy may prevent patients from receiving the most effective therapy. This review was undertaken to identify evidence-based preventive premedication strategies that reduce the likelihood of HSR in the first instance and improve the safety of subsequent infusions in patients who have demonstrated HSR to a certain class of chemotherapy. PubMed was searched until October 2021 using the key words: "hypersensitivity to chemotherapeutic drugs," "hypersensitivity to antineoplastic agents," "taxanes hypersensitivity," "platinum compound hypersensitivity," "premedication," "dexamethasone," "prednisone," "hydrocortisone," "antihistamine," "diphenhydramine," "cetirizine," "famotidine," "meperidine," "aspirin," "ibuprofen," and "montelukast." The search was restricted to articles published in English. A total of 73 abstracts were selected for inclusion in the review. Most premedication regimens have been derived empirically rather than determined through randomized trials. Based on the available evidence, we provide an update on likely HSR mechanisms and a practical guide for classifying systemic HSR. The evidence indicates that a combination of prevention strategies using newer antihistamines, H2 antagonists, leukotriene receptor antagonists, and corticosteroids and other interventions used judiciously reduces the occurrence and severity of HSR and improves safety.

Successful Desensitization to mRNA COVID-19 Vaccine in a Case Series of Patients With a History of Anaphylaxis to the First Vaccine Dose.

Background: Coronavirus disease 2109 (COVID-19) vaccines have recently been approved to curb the global pandemic. The risk of allergic reactions to the vaccine polyethylene glycol (PEG) component has raised significant public concern. Desensitization is suggested in cases of vaccine related hypersensitivity reactions. After comprehensive literature review on the topic, our aim was to establish a safe and effective desensitization protocol for patients with suspected or confirmed immediate type hypersensitivity reactions to the COVID-19 vaccine. Methods: Participants were referred to the McGill University Health Center (MUHC) Allergy-Immunology department for clinical evaluation following a reported reaction to their first dose of Moderna® mRNA-1273 or Pfizer-BioNTech® BNT162b2 vaccines. They underwent skin prick testing (SPT) with higher and lower molecular weight (MW) PEG and polysorbate 80, as per published protocols. Their second dose was administered following a desensitization protocol consisting of multiple dose-administration steps followed by a 60-min observation period. Results: Among a cohort of 142 patients with an increased risk for allergic reactions to the COVID-19 vaccines, six individuals were selected to undergo desensitization. All were female with allergic background including chronic spontaneous urticaria, anaphylaxis to medications, and/or vaccines. The main symptom after their first dose was difficulty swallowing with lightheadedness or immediate urticaria, angioedema, and/or dizziness. Two patients had positive skin testing. One patient was on chronic antihistamines which resulted in an inconclusive PEG skin test and the skin testing was negative for the three other patients. During the desensitization, two patients reported cutaneous symptoms of an immediate reaction and were managed with antihistamines. One of these patients also complained of ear pressure and had a drop in her systolic blood pressure, treated with intravenous fluids. Conclusion: This study suggests that some individuals with an immediate-type hypersensitivity reaction to their first dose of mRNA COVID-19 vaccine may safely receive their second dose using a desensitization protocol. The success of this desensitization protocol is a step forward in the fight against COVID-19, allowing more individuals to be immunized.