Project description:Vaccines against COVID-19 (and its emerging variants) are an essential global intervention to control the current pandemic situation. Vaccines often cause adverse events; however, the vast majority of adverse events following immunization (AEFI) are a consequence of the vaccine stimulating a protective immune response, and not allergic in etiology. Anaphylaxis as an AEFI is uncommon, occurring at a rate of less than 1 per million doses for most vaccines. However, within the first days of initiating mass vaccination with the Pfizer-BioNTech COVID-19 vaccine BNT162b2, there were reports of anaphylaxis from the United Kingdom and United States. More recent data imply an incidence of anaphylaxis closer to 1:200,000 doses with respect to the Pfizer-BioNTech vaccine. In this position paper, we discuss the background to reactions to the current COVID-19 vaccines and relevant steps to mitigate against the risk of anaphylaxis as an AEFI. We propose a global surveillance strategy led by allergists in order to understand the potential risk and generate data to inform evidence-based guidance, and thus provide reassurance to public health bodies and members of the public.
Project description:In the era of novel coronavirus epidemics, vaccines against coronavirus disease 2019 (COVID-19) have been recognized as the most effective public health interventions to control the pandemic. An adverse event following immunization (AEFI) is defined as any untoward occurrence following immunization, and the majority of AEFIs are caused by protective immune responses stimulated by vaccines. Most of the reported AEFIs are not serious, and many are not immunologically mediated or even reproducible on re-exposure. However, uncommon severe allergic adverse reactions, such as anaphylaxis or other allergic reactions, can occur after vaccinations. Confirmed allergic reactions to vaccines may be caused by residual non-human protein, preservatives, or stabilizers in the vaccine formulation (also known as excipients). There are 2 main potential allergenic/immunogenic excipients in COVID-19 vaccines, polyethylene glycol (PEG) and polysorbate 80. PEG, also known as macrogol, is an ingredient in various laxatives and injectable formulations, such as depot steroids. Polysorbate 80 is present in various medical products, creams, ointments, lotions, and medication tablets. Contraindications to the administration of COVID-19 vaccines include a previous history of severe allergic reactions to the first dose of COVID-19 vaccine or proven hypersensitivity to a vaccine component, such as PEG or polysorbate 80. Anaphylaxis or other allergic reactions following immunization can cause fear and loss of confidence in the safety of vaccines among the public. A better understanding of these events is thought to help alleviate concerns about the current COVID-19 vaccines and provide reassurance to the general population by analyzing the exact incidence of anaphylaxis and potential risk factors. COVID-19 vaccine-associated anaphylaxis could be prevented and managed by risk stratification based on our local and global experience.
Project description:In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, virus genetic variants are still circulating among vaccinated individuals with different symptomatology disease cases. Understanding the protective or disease associated mechanisms in vaccinated individuals is relevant to advance in vaccine development and implementation. To address this objective, serum protein profiles were characterized by quantitative proteomics and data analysis algorithms in four cohorts of vaccinated individuals uninfected and SARS-CoV-2 infected with asymptomatic, nonsevere and severe disease symptomatology. The results showed that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective or disease associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In nonsevere cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins including the Spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.
Project description:BackgroundPolyethylene glycol (PEG) may elicit anaphylaxis to COVID-19 mRNA vaccines, and guidance for patients at risk is needed.MethodsIn retrospective patients with PEG allergy collected from 2006 till 2019, clinical, skin, and basophil activation test (BAT) characteristics discriminative for PEG allergy were analyzed and compared with the literature. In 421 prospective real-life patients asking for allergy workup for COVID-19 vaccine hypersensitivity in 2020/2021, risk assessment was performed and tolerance of the recommended vaccination approach was assessed.ResultsTen patients with PEG allergy were found in the retrospective cohort. Patients reacted with immediate anaphylaxis (100%) not only to PEG-based laxatives/bowel preparations or injections, but also to cold medication, antiseptics, analgetics, or antibiotics. Skin tests ± BAT with PEG ± elicitors were positive in 10/10. Provocation tests were positive in 7/9 patients. From the prospective cohort, 370/421 patients self-reporting increased risk for vaccine allergy lacked criteria necessitating allergy workup and were recommended for routine vaccination. A total of 51/421 patients were tested, and three (6%) with PEG allergy were identified, whereas 48 patients remained negative in skin tests. Vaccination was recommended in all those patients. No hypersensitivity reactions were reported to vaccination including six PEG-allergic patients tolerating COVID-19 vaccination.ConclusionsTaking a detailed history excluded PEG allergy in most referred patients and enabled direct safe vaccination. Immediate urticaria/anaphylaxis to typical elicitors identified patients requiring PEG allergy workup. Skin tests ± BAT identified PEG allergy and helped to select the vaccine and the vaccination approach. Even PEG-allergic patients can tolerate COVID-19 vaccines.
Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.
Project description:Blood collected from adults pre vaccination and post vaccination to study the immune effects of COVID-19 vaccination and how they relate to antibody and T-cell responses.
Project description:BackgroundCoronavirus 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.MethodsParticipants 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.ResultsAmong 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.ConclusionThis 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.
Project description:IntroductionIn mid-February, the nationwide immunization plan for the prevention of coronavirus disease 2019 (COVID-19) started in Japan (at first primarily focused on health professionals) using an mRNA-based vaccine (Pfizer/BioNTech). During the phase-in period from February to March, attention was focused on post-vaccination anaphylaxis and anaphylactoid symptoms from the viewpoint of ensuring the safety of the vaccination program.ObjectiveThe aim of this report was to provide an update on the status of anaphylaxis and anaphylactoid symptoms occurring after vaccination for COVID-19, as reported under the Adverse Event Following Immunization (AEFI) reporting system in Japan.MethodsThe Pharmaceutical and Medical Devices Agency (PMDA) received AEFI reports from health professionals and manufacturers under the reporting system for AEFI after vaccination for COVID-19, which has been in operation since mid-February 2021. Reported AEFIs of anaphylaxis and anaphylactoid symptoms were assessed using the Brighton Collaboration Criteria to assess diagnostic certainty.Results1-month since Japan started the vaccination program for COVID-19 in February 2021, 578,835 doses have been administered to health professionals, with the PMDA receiving 181 suspected event reports of anaphylaxis and anaphylactoid symptoms. In 171 of these 181 cases, women developed these symptoms. Among 181 cases evaluated according to the Brighton Collaboration Criteria, 47 cases (26%) were classified as level 1-3 (reporting rate: 8.1/100,000 doses).ConclusionThe results appear similar to reported AEFIs in foreign studies of coronavirus vaccine administration to health professionals, although the reporting rate was higher. Further work is needed to examine the causal relationship of anaphylaxis reactions to coronavirus vaccine administration. Issues of multiple reporting and possible sex/age bias also remain to be analyzed.
Project description:Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against SARS-CoV-2. Previous studies have shown divergent results regarding protective or damaging immunity induced by prior exposure to sCoVs. It is still unknown whether pre-existing humoral immunity may play a role in the vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera in healthy volunteers before and after immunization with inactivated SARS-CoV-2 vaccines, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level before vaccine immunization, as well as the relationship between pre-existing sCoVs immunity and vaccine-induced neutralization.