Incidence and management of the main serious adverse events reported after COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2n first appeared in Wuhan, China in 2019. Soon after, it was declared a pandemic by the World Health Organization. The health crisis imposed by a new virus and its rapid spread worldwide prompted the fast development of vaccines. For the first time in human history, two vaccines based on recombinant genetic material technology were approved for human use. These mRNA vaccines were applied in massive immunization programs around the world, followed by other vaccines based on more traditional approaches. Even though all vaccines were tested in clinical trials prior to their general administration, serious adverse events, usually of very low incidence, were mostly identified after application of millions of doses. Establishing a direct correlation (the cause-effect paradigm) between vaccination and the appearance of adverse effects has proven challenging. This review focuses on the main adverse effects observed after vaccination, including anaphylaxis, myocarditis, vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome, and transverse myelitis reported in the context of COVID-19 vaccination. We highlight the symptoms, laboratory tests required for an adequate diagnosis, and briefly outline the recommended treatments for these adverse effects. The aim of this work is to increase awareness among healthcare personnel about the serious adverse events that may arise post-vaccination. Regardless of the ongoing discussion about the safety of COVID-19 vaccination, these adverse effects must be identified promptly and treated effectively to reduce the risk of complications.

Assessment of potential adverse events following the 2022-2023 seasonal influenza vaccines among U.S. adults aged 65 years and older.

BACKGROUND: While safety of influenza vaccines is well-established, some studies have suggested potential associations between influenza vaccines and certain adverse events (AEs). This study examined the safety of the 2022-2023 influenza vaccines among U.S. adults ≥ 65 years. METHODS: A self-controlled case series compared incidence rates of anaphylaxis, encephalitis/encephalomyelitis, Guillain-Barré Syndrome (GBS), and transverse myelitis following 2022-2023 seasonal influenza vaccinations (i.e., any, high-dose or adjuvanted) in risk and control intervals among Medicare beneficiaries ≥ 65 years. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) adjusted for event-dependent observation time and seasonality. Analyses also accounted for uncertainty from outcome misclassification where feasible. For AEs with any statistically significant associations, we stratified results by concomitant vaccination status. RESULTS: Among 12.7 million vaccine recipients, we observed 76 anaphylaxis, 276 encephalitis/encephalomyelitis, 134 GBS and 75 transverse myelitis cases. Only rates of anaphylaxis were elevated in risk compared to control intervals. With all adjustments, an elevated, but non-statistically significant, anaphylaxis rate was observed following any (IRR: 2.40, 95% CI: 0.96-6.03), high-dose (IRR: 2.31, 95% CI: 0.67-7.91), and adjuvanted (IRR: 3.28, 95% CI: 0.71-15.08) influenza vaccination; anaphylaxis IRRs were 2.54 (95% CI: 0.49-13.05) and 1.64 (95% CI: 0.38-7.05) for persons with and without concomitant vaccination, respectively. CONCLUSIONS: Rates of encephalitis/encephalomyelitis, GBS, or transverse myelitis were not elevated following 2022-2023 seasonal influenza vaccinations among U.S. adults ≥ 65 years. There was an increased rate of anaphylaxis following influenza vaccination that may have been influenced by concomitant vaccination.

Disparities in pediatric anaphylaxis triggers and management across Asia.

BACKGROUND: The epidemiology and management of anaphylaxis are not well-reported in Asia. METHODS: A regional pediatric anaphylaxis registry was established by the Asia-Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia-Pacific region. Pediatric patients below 18 years presenting with anaphylaxis across four Asian countries/cities (Thailand, Singapore, Hong Kong (HK), and Qingdao) were included. Allergen triggers, symptoms, anaphylaxis severity, and management were compared. RESULTS: Between 2019 and 2022, 721 anaphylaxis episodes in 689 patients from 16 centers were identified. The mean age at anaphylaxis presentation was 7.0 years (SD = 5.2) and 60% were male. Food was the most common trigger (62%), particularly eggs and cow's milk in children aged 3 years and below. In school-age children, nut anaphylaxis was most common in HK and Singapore, but was rare in the other countries, and wheat was the top allergen in Bangkok. Shellfish anaphylaxis was most common in children aged 7-17. Adrenaline was administered in 60% of cases, with 9% given adrenaline before hospital arrival. Adrenaline devices were prescribed in up to 82% of cases in Thailand but none in Qingdao. CONCLUSIONS: The APRA identified food as the main trigger of anaphylaxis in children, but causative allergens differed even across Asian countries. Fewer than two-thirds of cases received adrenaline treatment, pre-hospital adrenaline usage was low, and adrenaline device prescription remained suboptimal. The registry recognizes an unmet need to strengthen anaphylaxis care and research in Asia-Pacific.

Deep Learning Model for Automated Trainee Assessment During High-Fidelity Simulation.

PROBLEM: Implementation of competency-based medical education has necessitated more frequent trainee assessments. Use of simulation as an assessment tool is limited by access to trained examiners, cost, and concerns with interrater reliability. Developing an automated tool for pass/fail assessment of trainees in simulation could improve accessibility and quality assurance of assessments. This study aimed to develop an automated assessment model using deep learning techniques to assess performance of anesthesiology trainees in a simulated critical event. APPROACH: The authors retrospectively analyzed anaphylaxis simulation videos to train and validate a deep learning model. They used an anaphylactic shock simulation video database from an established simulation curriculum, integrating a convenience sample of 52 usable videos. The core part of the model, developed between July 2019 and July 2020, is a bidirectional transformer encoder. OUTCOMES: The main outcome was the F1 score, accuracy, recall, and precision of the automated assessment model in analyzing pass/fail of trainees in simulation videos. Five models were developed and evaluated. The strongest model was model 1 with an accuracy of 71% and an F1 score of 0.68. NEXT STEPS: The authors demonstrated the feasibility of developing a deep learning model from a simulation database that can be used for automated assessment of medical trainees in a simulated anaphylaxis scenario. The important next steps are to (1) integrate a larger simulation dataset to improve the accuracy of the model; (2) assess the accuracy of the model on alternative anaphylaxis simulations, additional medical disciplines, and alternative medical education evaluation modalities; and (3) gather feedback from education leadership and clinician educators surrounding the perceived strengths and weaknesses of deep learning models for simulation assessment. Overall, this novel approach for performance prediction has broad implications in medical education and assessment.

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.

Drug allergy in primary care: systematic review to support quality improvement initiative of management and optimization of healthcare pathways.

PURPOSE OF REVIEW: The aim of this study was to review the practice of general practitioners (GPs) in regard to the diagnosis and management of drug hypersensitivity reactions (DHRs) to identify major challenges and to facilitate the development of decision support tools to GPs confronted with DHRs patients. RECENT FINDINGS: DHRs are still a challenge in the GPs clinical practice, which implies difficulties in clinical decisions and referral to allergy specialists. SUMMARY: DHRs can range from mild to severe and even life-threatening. Drugs are the main cause of anaphylaxis deaths in most countries. Most DHRs are firstly seen by GPs, paediatricians or emergency doctors. However, our systematic review demonstrated difficulties in differentiating DHRs from other drug side effects. Most DHRs epidemiological data are from hospital and emergency departments, which may not reflect the real-life experience in primary care. GPs should be aware of the alert signs of DHRs: the involvement of other systems beyond the skin and/or atypical skin/ mucosal involvement, which mandated immediate referral to an emergency department. Data still stress difficulties in the recognition of DHRs clinical manifestations and highlight the need for decision aids to support their management by GPs. Structured clinical history and clinical examination are key diagnostic tools. Reasons for referring to allergy specialists based on the literature are to investigate cause, to undergo specific procedure, such as desensitization and to identify well tolerated, alternative drugs.

Analysis of the Safety of Drug Allergy Workups in a Spanish University Hospital: Drug Characteristics, Type of Reaction, and Patients' Age at the Initial Assessment.

INTRODUCTION: The drug provocation test (DPT) is the gold standard for the drug allergy workup; however, it is not free from severe adverse reactions. Our aim was to obtain robust data that predict a reaction during or after the DPT at the first contact with the patient in the allergy outpatient clinic. METHODS: The population of this cross-sectional study comprised all patients undergoing a drug allergy workup (clinical assessment, specific IgE, or skin tests, or DPT) at University Hospital Fundacion Alcorcon in 2016. DPTs were performed until therapeutic doses were reached, and late reactions were checked. The clinical disorders assessed in our study were classified mainly as absence of allergic reactions, morbilliform rash, urticaria, anaphylaxis, and other cutaneous disorders. RESULTS: Physicians from the Allergy Unit programmed drug allergy workups in 977 patients (median age, 52 years; women, 64.54%). DPTs were not performed for 165 drugs involved in the reactions. Patients who did not undergo DPT were older than patients who did (positive or negative) (p = 0.0001). Positive DPT results were detected in 6.00% of DPTs performed, and most were for amoxicillin and metamizole (15-25% each). Multinomial logistic regression showed that positive reactions were more probable after DPT if the same clinical disorder was diagnosed at the first visit, including the episodes not considered allergic episodes (OR = 0.2, <0.01), except for anaphylaxis, which favored not performing DPTs (OR = 11, p < 0.001). CONCLUSION: We conclude that clinical practice in the diagnosis of drug allergy in our Allergy Department is safe, without over-diagnosis.

The Need for Required Stock Epinephrine in All Schools: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee.

Epinephrine is the first line of treatment for anaphylaxis that can occur outside a medical setting in community environments such as schools. Patients with diagnosed IgE-mediated food allergy at risk of anaphylaxis are prescribed self-injectable epinephrine and given an individualized anaphylaxis action plan. As students, such patients/families provide their school with completed medication forms, a copy of their anaphylaxis plan, and additional student-specific epinephrine. However, students approved to self-carry prescribed self-injectable epinephrine may forget to do so or have other reasons for lacking prescribed epinephrine such as familial inability to fill the prescription due to cost or other access barriers. Undiagnosed students lacking prescribed epinephrine may also experience anaphylaxis at school. The presence of non-student-specific school stock epinephrine allows school nurses and other staff the ability to treat anaphylaxis onsite while awaiting Emergency Medical Services. Notably, not all states legally mandate K-12 schools to stock epinephrine. In states with laws only voluntarily allowing schools to stock epinephrine, it provides the ability to opt-out. Herein, we present a comprehensive review of barriers to school stock epinephrine, related improvement strategies, and workgroup recommendations supporting the need for mandated stock epinephrine in all schools in every state. Proposed solutions include ensuring legal immunity from liability for prescribers; advocacy for legislation to stabilize cost of self-injectable epinephrine; educational initiatives to schools promoting merits and safety of epinephrine and related anaphylaxis training; and partnerships between patient advocacy groups, medical and nursing organizations, public health departments and other health professionals to promote laws and district policies addressing need for stock epinephrine and school nurses to train and supervise school staff.

Background rates of adverse events of special interest for COVID-19 vaccine safety monitoring in the United States, 2019-2020.

BACKGROUND: The U.S. Food and Drug Administration (FDA) Biologics Effectiveness and Safety (BEST) Initiative conducts active surveillance of adverse events of special interest (AESI) after COVID-19 vaccination. Historical incidence rates (IRs) of AESI are comparators to evaluate safety. METHODS: We estimated IRs of 17 AESI in six administrative claims databases from January 1, 2019, to December 11, 2020: Medicare claims for adults ≥ 65 years and commercial claims (Blue Health Intelligence®, CVS Health, HealthCore Integrated Research Database, IBM® MarketScan® Commercial Database, Optum pre-adjudicated claims) for adults < 65 years. IRs were estimated by sex, age, race/ethnicity (Medicare), and nursing home residency (Medicare) in 2019 and for specific periods in 2020. RESULTS: The study included >100 million enrollees annually. In 2019, rates of most AESI increased with age. However, compared with commercially insured adults, Medicare enrollees had lower IRs of anaphylaxis (11 vs 12-19 per 100,000 person-years), appendicitis (80 vs 117-155), and narcolepsy (38 vs 41-53). Rates were higher in males than females for most AESI across databases and varied by race/ethnicity and nursing home status (Medicare). Acute myocardial infarction (Medicare) and anaphylaxis (all databases) IRs varied by season. IRs of most AESI were lower during March-May 2020 compared with March-May 2019 but returned to pre-pandemic levels after May 2020. However, rates of Bell's palsy, Guillain-Barré syndrome, narcolepsy, and hemorrhagic/non-hemorrhagic stroke remained lower in multiple databases after May 2020, whereas some AESI (e.g., disseminated intravascular coagulation) exhibited higher rates after May 2020 compared with 2019. CONCLUSION: AESI background rates varied by database and demographics and fluctuated in March-December 2020, but most returned to pre-pandemic levels after May 2020. It is critical to standardize demographics and consider seasonal and other trends when comparing historical rates with post-vaccination AESI rates in the same database to evaluate COVID-19 vaccine safety.

Food allergy in the World Health Organization's International Classification of Diseases (ICD)-11.

There are increasing global data regarding the prevalence of food allergy and food-induced anaphylaxis. However, knowledge in morbidity and mortality epidemiological data is still not optimal, and international comparable standards remain poorly accessed. This information could in turn support better clinical practice and possibly prevent future severe reactions and avoidable fatalities. The International Classification of Diseases (ICD) is the standard diagnostic tool used for epidemiology, health management, and clinical purposes supported by the World Health Organization (WHO). It is also used to determine health care payment and reimbursement of providers and health care services in hospitals. Thanks to the academic and technical efforts under the ALLERGY in ICD-11 initiative the pioneer "Allergy and hypersensitivity conditions" section has been built under the "Disorders of the Immune System" chapter of the ICD-11. The "Food hypersensitivity" (FH) subsection is classified under the "Complex allergic or hypersensitivity conditions" section and "Food-induced anaphylaxis" is under the "Anaphylaxis" section. In order to inform the development of strategies to reduce preventable FHs/food allergies, the burden of disease in different healthcare settings and patient populations and their common etiologies need to be understood. Besides, greater specificity regarding clinical conditions and services delivered will provide payers, policy makers, and providers with better information to make major refinements to countries payment and reimbursement systems, including the design and implementation of pay-for-performance program.The new classification addressed to FHs will enable the collection of more accurate epidemiological data to support quality management of patients with FHs/food allergies, and better facilitate health care planning and decision-making and public health measures to prevent and reduce their morbidity and mortality. The improved logic and standardized definitions through the ICD-11 (and other WHO classifications) will also facilitate international comparisons of quality care and the sharing of best practice globally.

[Allergy risk assessment and surveillance]. / Évaluation et surveillance du risque allergique.

The assessment of a patient's allergic risk can be based on the ABCDE methodology to be standardized. Hospital monitoring should be routine in case of signs of anaphylaxis.

Epinephrine Auto-Injector Prescription and Use: A Retrospective Analysis and Clinical Risk Assessment of Adult Patients Sensitized to Lipid Transfer Protein.

Lipid transfer proteins (LTPs) are widely widespread plant food allergens which represents the main cause of food allergy in adults living in the Mediterranean basin. The purpose of this study was to investigate in LTP patients the actual use of prescribed epinephrine auto-injector and appropriateness of its prescription. In addition, we investigated in these patients: (1) occurrence of new food reaction in the following three years after to diagnosis; (2) need and number of access to emergency services; (3) presence of possible predictive factors to further food reactions. One-hundred sixty-five adult patients sensitized to LTPs have been included. During follow-up, we recorded 68 further reactions, most of them (77.9%) characterized by local symptoms; rarely the patients required an emergency-department visits (16.1%) and only one patient (1.7%) used the epinephrine auto-injector. The patients with a previous history of anaphylaxis at baseline turned back to access to emergency services also during the follow-up (p = 0.006). The majority of patients with recorded systemic reactions (p = 0.004) and treated in an emergency room (p = 0.028) did not have any co-factor-enhanced at diagnosis. We noted an association between platanus pollen sensitization and severity of further reactions during the follow-up (p = 0.026). Epinephrine auto-injector were prescribed to 108/165 patients (65.5%) with an over-prescription rate of 25%. The unforeseeable clinical presentation of LTP allergic reactions and the eventual role played by the cofactor make necessary schedule a follow-up to monitor the patients over time and to assess the actual use of epinephrine auto injectors prescribed.

Economic burden of drug-induced anaphylaxis: what can we do better?

PURPOSE OF REVIEW: This systematic review evaluates published data related to the economic burden of drug-induced anaphylaxis (DIA) to understand preventive cost saving measures that could reduce the burden of these conditions. RECENT FINDINGS: Although DIA has a relevant societal impact, there are limited and heterogenous available data related to its cost. Direct costs related to the management of acute phase of DIA was estimated by $529.6 to $3125, depending on the number of emergency room visits/hospitalizations, emergency kits and transports in ambulance. Direct costs of investigations of DIA varied from $288 to $2292.95 and the desensitization was estimated by $6796. Main variables for this were: personnel, allergy screening procedures, medical consumables and space cost. The mean indirect cost was based on a mean absenteeism of 3 days per DIA corresponding to $381.2. SUMMARY: More than reviewing the published data, we were able to identify variables that, if correctly managed, can reduce the economic burden of DIA, such as adjusting the timing of referral and etiological diagnosis, identification of potential risk and/or co-factors, correct written recommendations to patients. The evidence presented highlights the need of optimization of healthcare patients to patients suffering from DIA.

Assessment and management of allergy history with a novel mRNA vaccine.

Context: Tertiary care hospital provided onsite COVID-19 vaccine roll out as a work benefit for all care team members with medically supervised waiting period at the time of the distribution of the first round of the novel mRNA COVID-19 vaccines. Little was known about the immediate hypersensivity reactions or what might predispose to cross reactivity. Objective: We developed a working protocol to continuously track the vaccines administered, the patient history of allergy and hypersensistivity, the reactions observed and the care plan developed (determination of allergy to mRNA vaccines or normal vaccine response). Continuous process improvement allowed us to change protocols as the CDC developed guidance. Every patient was observed for at least 15 minutes and every reaction was reviewed by a physician supervising the waiting area. We aimed to determine if there were predictors of adverse, immediate reaction to the vaccine and to assess prevalence of risk factors (history of allergy to polyethylene Glycol or polysorbate; allergy to other injectable medication or vaccines; hypersensitivity to multiple substances). Study Design: Cohort study of all employees who received a first mRNA COVID-19 vaccine between December 16 and January 7th. Descriptive statistics were developed with demographic and medical history recorded, reactions noted and treatment given. Setting or Dataset: Tertiary care hospital in urban area. Population Studied: Employees who received an mRNA COVID-19 vaccine. Intervention/Instrument: Clinical records from employee vaccine clinic. Outcome Measures: Record of immediate response, determination of allergy. Results: We served over 7000 individuals with approximately 10% having a history of anaphylactic reaction. We had fewer with history of anaphylaxis to medications or vaccines. We delivered these vaccines safely, and observed three cases of immediate anaphylaxis on first dose of mRNA and over 50 cases of immediate allergic hypersensitivity. We did not see any patterns that predicted these reactions (gender, age or medical history). Expected Outcomes: We used this data to inform our employee health vaccination campaign and to inform the health system as strategies and safety protocols for vaccination of the population were developed.

Clinical and quality of life assessment in patients with latex allergy during COVID-19 pandemic: Possible protective role of continuous latex immunotherapy.

Introduction: During COVID-19 pandemic, the massive use of Personal Protective Equipment could provoke severe adverse reactions in latex allergy patients and could negatively affect their quality of life. Methods: Trough a survey the study aimed: (a) to evaluate the incidence of allergic reactions in patients with latex allergy during the SARS-CoV-2 pandemic; (b) to evaluate the protective role of continuous latex sublingual immunotherapy (SLIT) during this period; and (c) to evaluate quality of life of natural rubber latex allergy (NRLA) patients during the pandemic. Results: 67 patients (9 males and 58 females, mean age of 45.9 ± 11.4 years) suffering from latex allergy were included in the present study. We recorded among our patients 13 cases (34.2%) of urticarial/angioedema (U/A), 9 cases (23.6%) of respiratory symptoms (dyspnoea, shortness of breath and wheezing) and 7 cases (18.4%) of anaphylaxis. In patients who underwent continuous SLIT, we observed less cases of U/A (p < 0.001), respiratory symptoms (p < 0.001), anaphylaxis (p = 0.003), hospitalizations (p = 0.014) and a lower therapy administration. We compared the results of SF-36 questionnaire in patients who underwent continuous and not-continuous SLIT with a significance differences score between these two groups. Conclusions: Our study is the first that investigated the clinical and quality of life effects of COVID-19 pandemic in NRLA patients.

Acute At-Home Management of Anaphylaxis: 911: What Is the Emergency?

The appropriate at-home management of anaphylaxis begins with patient education on recognition and treatment, especially when and how to use epinephrine. Delayed administration of epinephrine as well as having severe symptoms and needing multiple doses of epinephrine to treat symptoms are risk factors for biphasic anaphylaxis. The successful implementation of at-home management of anaphylaxis requires appropriate patient selection and an algorithmic approach that recommends activation of emergency medical services (EMS) when the patient does not adequately respond to at-home administration of epinephrine or there are extenuating patient-related circumstances. Fortunately, approximately 98% of anaphylactic episodes respond to 2 or fewer doses of epinephrine, the standard prescription used for epinephrine autoinjectors; fatal anaphylaxis is very rare, as low as 0.002 deaths/million person-years; and biphasic reactions are uncommon (∼5%), and only extremely rarely lethal. Thus, most common concerns leading to recommended EMS activation and emergency department visits after epinephrine administration are generally unsubstantiated. Furthermore, emergency department visits do not always lead to better treatment and drive health care costs higher. Open communications with patients and families regarding risks and benefits of at-home management and observation versus EMS activation and emergency department evaluation after epinephrine administration for anaphylaxis are essential. However, we believe the data indicate that it is time to reconsider the often used and taught approach that recommends EMS activation whenever epinephrine is used.