A compilation answering 50 questions on monkeypox virus and the current monkeypox outbreak.

The current monkeypox disease (MPX) outbreak constitutes a new threat and challenge for our society. With more than 55,000 confirmed cases in 103 countries, World Health Organization declared the ongoing MPX outbreak a Public Health Emergency of International Concern (PHEIC) on July 23, 2022. The current MPX outbreak is the largest, most widespread, and most serious since the diagnosis of the first case of MPX in 1970 in the Democratic Republic of the Congo (DRC), a country where MPX is an endemic disease. Throughout history, there have only been sporadic and self-limiting outbreaks of MPX outside Africa, with a total of 58 cases described from 2003 to 2021. This figure contrasts with the current outbreak of 2022, in which more than 55,000 cases have been confirmed in just 4 months. MPX is, in most cases, self-limiting; however, severe clinical manifestations and complications have been reported. Complications are usually related to the extent of virus exposure and patient health status, generally affecting children, pregnant women, and immunocompromised patients. The expansive nature of the current outbreak leaves many questions that the scientific community should investigate and answer in order to understand this phenomenon better and prevent new threats in the future. In this review, 50 questions regarding monkeypox virus (MPXV) and the current MPX outbreak were answered in order to provide the most updated scientific information and to explore the potential causes and consequences of this new health threat.

White paper on peanut allergy - part 1: Epidemiology, burden of disease, health economic aspects.

Peanuts are Leguminosae, commonly known as the legume or pea family, and peanut allergy is among the most common food allergies and the most common cause of fatal food reactions and anaphylaxis. The prevalence of peanut allergy increased 3.5-fold over the past two decades reaching 1.4-2% in Europe and the United States. The reasons for this increase in prevalence are likely multifaceted. Sensitization via the skin appears to be associated with the development of peanut allergy and atopic eczema in infancy is associated with a high risk of developing peanut allergy. Until recently, the only possible management strategy for peanut allergy was strict allergen avoidance and emergency treatment including adrenaline auto-injector in cases of accidental exposure and reaction. This paper discusses the various factors that impact the risks of peanut allergy and the burden of self-management on peanut-allergic children and their caregivers.

COVID-19 vaccination of patients with allergies and type-2 inflammation with concurrent antibody therapy (biologicals) - A Position Paper of the German Society of Allergology and Clinical Immunology (DGAKI) and the German Society for Applied Allergology (AeDA).

BACKGROUND: After the beginning and during the worldwide pandemic caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), patients with allergic and atopic diseases have felt and still feel insecure. Currently, four vaccines against SARS-CoV-2 have been approved by the Paul Ehrlich Institute in Germany, and vaccination campaigns have been started nationwide. In this respect, it is of utmost importance to give recommendations on possible immunological interactions and potential risks of immunomodulatory substances (monoclonal antibodies, biologicals) during concurrent vaccination with the approved vaccines. MATERIALS AND METHODS: This position paper provides specific recommendations on the use of immunomodulatory drugs in the context of concurrent SARS-CoV-2 vaccinations based on current literature. RESULTS: The recommendations are covering the following conditions in which biologicals are indicated and approved: 1) chronic inflammatory skin diseases (atopic dermatitis, chronic spontaneous urticaria), 2) bronchial asthma, and 3) chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with atopic dermatitis or chronic spontaneous urticaria are not at increased risk for allergic reactions after COVID-19 vaccination. Nevertheless, vaccination may result in transient eczema exacerbation due to general immune stimulation. Vaccination in patients receiving systemic therapy with biologicals can be performed. Patients with severe asthma and concomitant treatment with biologicals also do not have an increased risk of allergic reaction following COVID-19 vaccination which is recommended in these patients. Patients with CRSwNP are also not known to be at increased risk for allergic vaccine reactions, and continuation or initiation of a treatment with biologicals is also recommended with concurrent COVID-19 vaccination. In general, COVID-19 vaccination should be given within the interval between two applications of the respective biological, that is, with a time-lag of at least 1 week after the previous or at least 1 week before the next biological treatment planned. CONCLUSION: Biologicals for the treatment of atopic dermatitis, chronic spontaneous urticaria, bronchial asthma, and CRSwNP should be continued during the current COVID-19 vaccination campaigns. However, the intervals of biological treatment may need to be slightly adjusted (DGAKI/AeDA recommendations as of March 22, 2021).

COVID-19 vaccination and allergen immunotherapy (AIT) - A position paper of the German Society for Applied Allergology (AeDA) and the German Society for Allergology and Clinical Immunology (DGAKI).

BACKGROUND: Vaccinations against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are intended to induce an immune response to protect against infection/disease. Allergen immunotherapy (AIT) is thought to induce a (different) immune response, e.g., to induce tolerance to allergens. In this position paper we clarify how to use AIT in temporal relation to COVID-19 vaccination. Four SARS-CoV-2 vaccines are currently approved in the EU, and their possible immunological interactions with AIT are described together with practical recommendations for use. MATERIALS AND METHODS: Based on the internationally published literature, this position paper provides specific recommendations for the use of AIT in temporal relation to a SARS-CoV-2 vaccination. RESULTS: AIT is used in 1) allergic rhinitis, 2) allergic bronchial asthma, 3) insect venom allergy, 4) food allergy (peanut). CONCLUSION: For the continuation of an ongoing AIT, we recommend an interval of 1 week before and after vaccination for subcutaneous immunotherapy (SCIT). For sublingual immunotherapy (SLIT) and oral immunotherapy (OIT), we recommend taking them up to the day before vaccination and a break of 2 - 7 days after vaccination. Initiation of a new SCIT, SLIT, or OIT should be delayed until 1 week after the day of the second vaccination. For SCIT, we generally recommend an interval of ~ 1 week to COVID-19 vaccination.

Cutaneous Adverse Reactions to COVID-19 Vaccines: Insights from an Immuno-Dermatological Perspective.

(1) Background: Numerous vaccines are under preclinical and clinical development for prevention of severe course and lethal outcome of coronavirus disease 2019 (COVID-19). In light of high efficacy rates and satisfactory safety profiles, some agents have already reached approval and are now distributed worldwide, with varying availability. Real-world data on cutaneous adverse drug reactions (ADRs) remain limited. (2) Methods: We performed a literature research concerning cutaneous ADRs to different COVID-19 vaccines, and incorporated our own experiences. (3) Results: Injection site reactions are the most frequent side effects arising from all vaccine types. Moreover, delayed cutaneous ADRs may occur after several days, either as a primary manifestation or as a flare of a pre-existing inflammatory dermatosis. Cutaneous ADRs may be divided according to their cytokine profile, based on the preponderance of specific T-cell subsets (i.e., Th1, Th2, Th17/22, Tregs). Specific cutaneous ADRs mimic immunogenic reactions to the natural infection with SARS-CoV-2, which is associated with an abundance of type I interferons. (4) Conclusions: Further studies are required in order to determine the best suitable vaccine type for individual groups of patients, including patients suffering from chronic inflammatory dermatoses.

Adverse rare events to vaccines for COVID-19: From hypersensitivity reactions to thrombosis and thrombocytopenia.

Vaccines for the prevention of coronavirus disease 2019 (COVID-19) started to be developed since the initiation of the COVID-19 pandemic. Up to now, four vaccines have been authorized by international agencies such as European Medicines Agency (EMA). Two are DNA vaccines (ChAdOx1 nCov-19 and Ad26.COV2.S) and two mRNA vaccines (BNT162b2 and mRNA-1273). The administration of the vaccines has been associated with a strong decrease in the infections by SARS-CoV-2 and deaths associated with it. However, in parallel to these results, some rare adverse events have also been described. In that sense, events of thrombosis, thrombocytopenia, and hemorrhage have been described in close temporal proximity to the administration of the DNA vaccines ChAdOx1 nCov-19 and Ad26.COV2.S, but also mRNA vaccines. Recent scientific reports have been released with updated information on the possible association of thrombotic thrombocytopenia and COVID-19 vaccines. On the other hand, since the initiation of the vaccination campaigns, adverse hypersensitivity reactions have been described after mRNA and DNA vaccines administration for COVID-19. Although globally these adverse events are rare, a high proportion of the world population will be exposed to these vaccines. For that reason, their safety and tolerance should be carefully considered. In this review, we provide an updated review of the last scientific findings that can explain the rare side effects that the vaccines for COVID-19 can produce.

Immunologically relevant aspects of the new COVID-19 vaccines-an ÖGAI (Austrian Society for Allergology and Immunology) and AeDA (German Society for Applied Allergology) position paper.

BACKGROUND: The vaccines against the coronavirus disease 2019 (COVID-19) approved in the European Union represent a decisive step in the fight against the pandemic. The application of these available vaccines to patients with pre-existing immunological conditions leads to a multitude of questions regarding efficacy, side effects and the necessary patient information. RESULTS: This review article provides insight into mechanisms of action of the currently available severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and summarises the current state of science as well as expert recommendations regarding tolerability of the vaccines. In addition, the potential to develop protective immune responses is determined. A special focus is given on patients under immunosuppression or in treatment with immunomodulatory drugs. Special groups of the population such as children, pregnant women and the elderly are also considered. CONCLUSION: Despite the need for a patient-specific risk-benefit assessment, the consensus among experts is that patients with immunological diseases in particular benefit from the induced immune protection after COVID-19 vaccination and do not have an increased risk of side effects.

Practical handling of allergic reactions to COVID-19 vaccines: A position paper from German and Austrian Allergy Societies AeDA, DGAKI, GPA and ÖGAI.

BACKGROUND: For the preventive treatment of the 2019 coronavirus disease (COVID-19) an unprecedented global research effort studied the safety and efficacy of new vaccine platforms that have not been previously used in humans. Less than one year after the discovery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral sequence, these vaccines were approved for use in the European Union (EU) as well as in numerous other countries and mass vaccination efforts began. The so far in the EU approved mRNA vaccines BNT162b2 and mRNA-1273 are based on similar lipid-based nanoparticle carrier technologies; however, the lipid components differ. Severe allergic reactions and anaphylaxis after COVID-19 vaccination are very rare adverse events but have drawn attention due to potentially lethal outcomes and have triggered a high degree of uncertainty. METHODS: Current knowledge on anaphylactic reactions to vaccines and specifically the new mRNA COVID-19 vaccines was compiled using a literature search in Medline, PubMed, as well as the national and international study and guideline registries, the Cochrane Library, and the Internet, with special reference to official websites of the World Health Organization (WHO), US Centers for Disease Control and Prevention (CDC), Robert Koch Institute (RKI), and Paul Ehrlich Institute (PEI). RESULTS: Based on the international literature and previous experience, recommendations for prophylaxis, diagnosis and therapy of these allergic reactions are given by a panel of experts. CONCLUSION: Allergy testing is not necessary for the vast majority of allergic patients prior to COVID-19 vaccination with currently licensed vaccines. In case of allergic/anaphylactic reactions after vaccination, allergy workup is recommended, as it is for a small potential risk population prior to the first vaccination. Evaluation and approval of diagnostic tests should be done for this purpose.

Practical handling of allergic reactions to COVID-19 vaccines

SummaryBackgroundFor the preventive treatment of the 2019 coronavirus disease (COVID-19) an unprecedented global research effort studied the safety and efficacy of new vaccine platforms that have not been previously used in humans. Less than one year after the discovery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral sequence, these vaccines were approved for use in the European Union (EU) as well as in numerous other countries and mass vaccination efforts began. The so far in the EU approved mRNA vaccines BNT162b2 and mRNA-1273 are based on similar lipid-based nanoparticle carrier technologies;however, the lipid components differ. Severe allergic reactions and anaphylaxis after COVID-19 vaccination are very rare adverse events but have drawn attention due to potentially lethal outcomes and have triggered a high degree of uncertainty.MethodsCurrent knowledge on anaphylactic reactions to vaccines and specifically the new mRNA COVID-19 vaccines was compiled using a literature search in Medline, PubMed, as well as the national and international study and guideline registries, the Cochrane Library, and the Internet, with special reference to official websites of the World Health Organization (WHO), US Centers for Disease Control and Prevention (CDC), Robert Koch Institute (RKI), and Paul Ehrlich Institute (PEI).ResultsBased on the international literature and previous experience, recommendations for prophylaxis, diagnosis and therapy of these allergic reactions are given by a panel of experts.ConclusionAllergy testing is not necessary for the vast majority of allergic patients prior to COVID-19 vaccination with currently licensed vaccines. In case of allergic/anaphylactic reactions after vaccination, allergy workup is recommended, as it is for a small potential risk population prior to the first vaccination. Evaluation and approval of diagnostic tests should be done for this purpose.

Allergy to COVID-19 vaccines: A current update.

Adverse allergic reactions due to the administration of the vaccines developed for the protection of coronavirus disease 2019 (COVID-19) have been reported since the initiation of the vaccination campaigns. Current analyses provided by the Center for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) in the United States have estimated the rates of anaphylactic reactions in 2.5 and 11.1 per million of mRNA-1273 and BNT162b2 vaccines administered, respectively. Although rather low, such rates could have importance due to the uncommon fact that a large majority of the world population will be subjected to vaccination with the aforementioned vaccines in the following months and vaccination will most likely be necessary every season as for influenza vaccines. Health regulators have advised that any subject with a previous history of allergy to drugs or any component of the vaccines should not be vaccinated, however, certain misunderstanding exists since allergy to specific excipients in drugs and vaccines are in occasions misdiagnosed due to an absence of suspicion to specific excipients as allergenic triggers or due to inaccurate labeling or nomenclature. In this review, we provide an updated revision of the most current data regarding the anaphylactic reactions described for BNT162b2 vaccine, mRNA-1273 vaccine, and AZD1222 vaccine. We extensively describe the different excipients in the vaccines with the potential to elicit systemic allergic reactions such as polyethylene glycol (PEG), polysorbates, tromethamine/trometamol, and others and the possible immunological mechanisms involved.

Allergenic components of the mRNA-1273 vaccine for COVID-19: Possible involvement of polyethylene glycol and IgG-mediated complement activation.

Following the emergency use authorization of the mRNA-1273 vaccine on the 18th of December 2020, two mRNA vaccines are in current use for the prevention of coronavirus disease 2019 (COVID-19). For both mRNA vaccines, the phase III pivotal trials excluded individuals with a history of allergy to vaccine components. Immediately after the initiation of vaccination in the United Kingdom, Canada, and the United States, anaphylactic reactions were reported. While the culprit trigger requires investigation, initial reports suggested the excipient polyethylene glycol 2000 (PEG-2000)-contained in both vaccines as the PEG-micellar carrier system-as the potential culprit. Surface PEG chains form a hydrate shell to increase stability and prevent opsonization. Allergic reactions to such PEGylated lipids can be IgE-mediated, but may also result from complement activation-related pseudoallergy (CARPA) that has been described in similar liposomes. In addition, mRNA-1273 also contains tromethamine (trometamol), which has been reported to cause anaphylaxis to substances such as gadolinium-based contrast media. Skin prick, intradermal and epicutaneous tests, in vitro sIgE assessment, evaluation of sIgG/IgM, and basophil activation tests are being used to demonstrate allergic reactions to various components of the vaccines.

Severe allergic reactions after COVID-19 vaccination with the Pfizer/BioNTech vaccine in Great Britain and USA: Position statement of the German Allergy Societies: Medical Association of German Allergologists (AeDA), German Society for Allergology and Clinical Immunology (DGAKI) and Society for Pediatric Allergology and Environmental Medicine (GPA).

Two employees of the National Health Service (NHS) in England developed severe allergic reactions following administration of BNT162b2 vaccine against COVID-19 (coronavirus disease 2019). The British SmPC for the BNT162b2 vaccine already includes reference to a contraindication for use in individuals who have had an allergic reaction to the vaccine or any of its components. As a precautionary measure, the Medicines and Healthcare products Regulatory Agency (MHRA) has issued interim guidance to the NHS not to vaccinate in principle in "patients with severe allergies". Allergic reactions to vaccines are very rare, but vaccine components are known to cause allergic reactions. BNT162b2 is a vaccine based on an mRNA embedded in lipid nanoparticles and blended with other substances to enable its transport into the cells. In the pivotal phase III clinical trial, the BNT162b2 vaccine was generally well tolerated, but this large clinical trial, used to support vaccine approval by the MHRA and US Food and Drug Administration, excluded individuals with a "history of a severe adverse reaction related to the vaccine and/or a severe allergic reaction (e.g., anaphylaxis) to a component of the study medication". Vaccines are recognized as one of the most effective public health interventions. This repeated administration of a foreign protein (antigen) necessitates a careful allergological history before each application and diagnostic clarification and a risk-benefit assessment before each injection. Severe allergic reactions to vaccines are rare but can be life-threatening, and it is prudent to raise awareness of this hazard among vaccination teams and to take adequate precautions while more experience is gained with this new vaccine.

Healthcare provision for insect venom allergy patients during the COVID-19 pandemic.

The population prevalence of insect venom allergy ranges between 3-5%, and it can lead to potentially life-threatening allergic reactions. Patients who have experienced a systemic allergic reaction following an insect sting should be referred to an allergy specialist for diagnosis and treatment. Due to the widespread reduction in outpatient and inpatient care capacities in recent months as a result of the COVID-19 pandemic, the various allergy specialized centers in Germany, Austria, and Switzerland have taken different measures to ensure that patients with insect venom allergy will continue to receive optimal allergy care. A recent data analysis from the various centers revealed that there has been a major reduction in newly initiated insect venom immunotherapy (a 48.5% decline from March-June 2019 compared to March-June 2020: data from various centers in Germany, Austria, and Switzerland). The present article proposes defined organizational measures (e.g., telephone and video appointments, rearranging waiting areas and implementing hygiene measures and social distancing rules at stable patient numbers) and medical measures (collaboration with practice-based physicians with regard to primary diagnostics, rapid COVID-19 testing, continuing already-initiated insect venom immunotherapy in the outpatient setting by making use of the maximal permitted injection intervals, prompt initiation of insect venom immunotherapy during the summer season, and, where necessary, using outpatient regimens particularly out of season) for the care of insect venom allergy patients during the COVID-19 pandemic.