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. 2021 Sep 30;76(10):2952–2964. doi: 10.1111/all.14838

Management of anaphylaxis due to COVID‐19 vaccines in the elderly

Jean Bousquet 1,2,3,✉, Ioana Agache 4, Hubert Blain 5, Marek Jutel 6,7, Maria Teresa Ventura 8, Margitta Worm 1, Stefano Del Giacco 9, Athanasios Benetos 10, Beatrice Maria Bilo 11,12, Wienczyslawa Czarlewski 13, Amir Hamzah Abdul Latiff 14, Mona Al‐Ahmad 15,16, Elizabeth Angier 17, Isabella Annesi‐Maesano 18, Marina Atanaskovic‐Markovic 19, Claus Bachert 20,21,22,23, Annick Barbaud 24,25, Anna Bedbrook 14, Kazi S Bennoor 26, Elena Camelia Berghea 27,28, Carsten Bindslev‐Jensen 29, Sergio Bonini 30, Sinthia Bosnic‐Anticevich 31,32, Knut Brockow 33, Luisa Brussino 34, Paulo Camargos 35, G Walter Canonica 36,37, Victoria Cardona 38,39, Pedro Carreiro‐Martins 40,41, Ana Carriazo 42, Thomas Casale 43, Jean‐Christoph Caubet 44, Lorenzo Cecchi 45, Antonio Cherubini 46, George Christoff 47, Derek K Chu 48, Alvaro A Cruz 49, Dejan Dokic 50, Yehia El‐Gamal† 51, Motohiro Ebisawa 52, Bernadette Eberlein 33, John Farrell 53, Montserrat Fernandez‐Rivas 54, Wytske J Fokkens 55,56, Joao A Fonseca 57,58, Yadong Gao 59, Gaëtan Gavazzi 60, Radoslaw Gawlik 61, Asli Gelincik 62, Bilun Gemicioğlu 63, Maia Gotua 64, Olivier Guérin 65, Tari Haahtela 66, Karin Hoffmann‐Sommergruber 67, Hans Jürgen Hoffmann 68,69, Maja Hofmann 1, Martin Hrubisko 70, Maddalena Illario 71, Carla Irani 72, Zhanat Ispayeva 73, Juan Carlos Ivancevich 74, Kaja Julge 75, Igor Kaidashev 76, Musa Khaitov 77, Edward Knol 78, Helga Kraxner 79, Piotr Kuna 80, Violeta Kvedariene 81,82, Antti Lauerma 83, Lan T T Le 84, Vincent Le Moing 85, Michael Levin 86, Renaud Louis 87, Olga Lourenco 88, Vera Mahler 89, Finbarr C Martin 90, Andrea Matucci 91, Branislava Milenkovic 92, Stéphanie Miot 5, Emma Montella 71, Mario Morais‐Almeida 93, Charlotte G Mortz 29, Joaquim Mullol 94,95, Leyla Namazova‐Baranova 96, Hugo Neffen 97, Kristof Nekam 98, Marek Niedoszytko 99, Mikaëla Odemyr 100, Robyn E O’Hehir 101, Yoshitaka Okamoto 102, Markus Ollert 103,104, Oscar Palomares 105, Nikolaos G Papadopoulos 106, Petr Panzner 107, Giovanni Passalacqua 108, Vincenzo Patella 109, Mirko Petrovic 110, Oliver Pfaar 111, Nhân Pham‐Thi 112, Davor Plavec 113,114, Todor A Popov 115, Marysia T Recto 116, Frederico S Regateiro 117,118,119, Jacques Reynes 85, Regina E Roller‐Winsberger 120, Yves Rolland 121, Antonino Romano 122,123, Carmen Rondon 124,125, Menachem Rottem 126,127, Philip W Rouadi 128, Nathalie Salles 129, Boleslaw Samolinski 130, Alexandra F Santos 131,132,133,134, Faradiba S Sarquis 135, Joaquin Sastre 136, Jos M G A Schols 137, Nicola Scichilone 138, Anna Sediva 139, Mohamed H Shamji 140,141, Aziz Sheikh 142, Isabel Skypala 143, Sylwia Smolinska 144,145, Milena Sokolowska 146, Bernardo Sousa‐Pinto 57,58,147, Milan Sova 148, Rafael Stelmach 149, Gunter Sturm 150,151, Charlotte Suppli Ulrik 152, Ana Maria Todo‐Bom 153, Sanna Toppila‐Salmi 66, Ioanna Tsiligianni 154,155, Maria Torres 156, Eva Untersmayr 157, Marilyn Urrutia Pereira 158, Arunas Valiulis 159,160, Joana Vitte 161,162, Alessandra Vultaggio 91, Dana Wallace 163, Jolanta Walusiak‐Skorupa 164, De‐Yun Wang 165, Susan Waserman 48, Arzu Yorgancioglu 166, Osman M Yusuf 167, Mario Zernotti 168, Mihaela Zidarn 169, Tomas Chivato 170, Cezmi A Akdis 171, Torsten Zuberbier 1, Ludger Klimek 172,173
PMCID: PMC8251336  PMID: 33811358

Abstract

Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID‐19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID‐19 vaccines due to high risk of death. In very rare instances, the COVID‐19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA‐EAACI‐EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID‐19 vaccines. Anaphylaxis to COVID‐19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.

Keywords: adrenaline, anaphylaxis, COVID‐19 vaccines, older (adults/people)

Abbreviations

ACE inhibitors

angiotensin converting enzyme inhibitor

ABCDE

Airway, Breathing, Circulation, Disability, Exposure

ARIA

Allergic Rhinitis and its Impact on Asthma

AT‐2‐antagonists

Angiotensin II receptor type 2

EAACI

European Academy of Allergy and Clinical Immunology

EuGMS

European Geriatric Medicine Society

ICU

intensive care unit

IM

intramuscular

IV

Intravenous

1. INTRODUCTION

Older adults (over 65 years of age), 1 , 2 especially men and/or those with diabetes, 3 hypertension, 4 and/or obesity, 5 are prone to severe COVID‐19. Older men have more severe COVID‐19 infections than women of the same age. 6 , 7 , 8 , 9 Frailty is a risk factor for mortality from COVID‐19. 10 , 11 The population residing in nursing homes generally includes subjects who are both old and suffering from multimorbidity. Residential context increases social contacts in the same setting. A large number of COVID‐19‐related deaths have been reported in nursing homes, 12 , 13 , 14 , 15 , 16 and recommendations to control COVID‐19 in these settings have been issued. 16 , 17 , 18 Discharge from hospitals to nursing homes also puts residents at risk.

In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID‐19 vaccines due to high risk of death.

There are several peculiarities of the immune response to COVID‐19 vaccines in older people. For example, vaccine‐induced local and systemic reactogenicity—such as pain, fatigue, headache, or fever—was generally lower in older recipients of mRNA‐based COVID‐19 vaccine than in younger ones during the clinical trial phases.

However, in very rare instances, COVID‐19 vaccines can induce anaphylaxis. 19 , 20 , 21 Anaphylaxis in older people is not uncommon and is often more severe than in younger adults. 22 Vaccinations are known to cause anaphylaxis, although very rarely. 23 , 24 The benefit of the vaccination clearly outweighs the risk of severe anaphylaxis reaction to the COVID‐19 vaccines, even in older people suffering from severe allergic diseases.

The staff responsible for vaccinating in nursing homes may come from different educational backgrounds and include primary care staff or geriatricians who may not have had much experience in the management of anaphylaxis. Potential rapid evaluation and differential diagnosis of symptoms are therefore important. Moreover, in many countries, the equipment is insufficient in nursing homes (eg, lack of emergency medication, no possibility to provide IV therapy or infusion).

An ARIA‐EAACI‐EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID‐19 vaccines.

2. ANAPHYLAXIS TO COVID‐19 VACCINES

Several adverse reactions are reported for the COVID‐19 vaccines. They are classified into very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), and not known (cannot be estimated from the available data). Currently, due to lack of sufficient confirmed data, anaphylaxis/hypersensitivity is included under the “not known” category.

Following the approval of the COVID‐19 vaccine BNT162b2 (Pfizer‐BioNTech), several severe anaphylaxis cases occurred within the first few days of public vaccination. 19 , 21 A first analysis of the data reported in the Vaccine Adverse Events Reporting System (VAERS, https://vaers.hhs.gov) of the United States showed an incidence of 11.1 cases of anaphylaxis per million doses of the COVID‐19 vaccine BNT162b2. The VAERS report of 18 January 2021 reports a rate of 5 anaphylaxis cases per million doses administered for the BNT162b2 and 2.8 per million for the Moderna vaccine. 25 Polyethylene glycol (PEG) contained in PEGylated excipients has been proposed to be an allergenic component of the vaccines. 26 The median age of patients with anaphylaxis was 40 years (range =27–60 years), and 90% of the reported cases occurred in women. 27 Allergic reactions often, but not always, occurred in people with a previous history of severe allergic reactions, many of them carrying an adrenaline (epinephrine) auto‐injector. Moreover, during the clinical trial phases, vaccine‐induced local and systemic reactogenicity, such as pain, fatigue, headache, or fever, was generally lower in older recipients of the mRNA‐based COVID‐19 vaccine than in younger ones. Similar reactions occurred with the Moderna vaccine albeit at a lower frequency (around 2.5 per million), but possibly more severe. 28

The COVID‐19 vaccines will be administered to billions of individuals worldwide and there are raised concerns that severe adverse reactions—requiring continuous alertness and careful management—might sometimes occur. With the current information, the European Academy of Allergy and Clinical Immunology (EAACI) stated its position for preliminary recommendations that are to be revised as soon as more data emerge. 21 , 27 , 29

3. SYMPTOMS OF ANAPHYLAXIS IN OLDER PEOPLE

The European Anaphylaxis Registry includes data from 1,123 patients over 65 years of age with anaphylactic reactions. These data are provided by tertiary referral centers specialized in allergology and/or dermatology in Austria, Bulgaria, France, Germany, Italy, Poland, Spain, and Switzerland. 30 In the registry, anaphylactic symptoms were similar in younger adults and older people, but their frequency differed: cardiovascular symptoms occurred more frequently in older people (80% compared to 75% in adults). This confirmed previous observations that in patients presenting with anaphylaxis at the Emergency Department, an age of 65 or older was associated with an increased likelihood of cardiovascular symptoms. 31 A major cardiovascular symptom was loss of consciousness (33%), while dizziness and tachycardia were more prevalent in younger adults. Cardiac arrest occurred in 3% of older persons and in 2% of younger adults. The skin was the most frequently involved organ system. Urticaria and angioedema are two clinical manifestations of anaphylaxis and usually appear before other symptoms. The severity of anaphylactic reactions in older patients without skin symptoms was increased in comparison to younger adults. Gastrointestinal symptoms occurred in a similar proportion in both groups. The respiratory system, especially dyspnea, was less frequently affected in older persons (63% compared to 70% in younger adults). However, cyanosis, syncope, and dizziness are highly predictive of shock development in older people. Severe anaphylactic reactions, including grade III (47%) and grade IV (4%) of the anaphylaxis Ring and Messmer classification, 32 were more prevalent in people aged 65+.

This registry indicates that symptoms are similar in younger/middle‐aged adults and older people but that they are more severe in the older age group (Figure 1). Adrenaline was administered in 30% of older patients. Hospitalization was required in 60%, and 19% of older patients were treated in an intensive care unit (ICU). Significantly more older people as compared to younger and middle‐aged adults with grade II and III anaphylaxis needed hospitalization and ICU care 32 (Figure 1 and Table 1). Considering different triggers of anaphylaxis, higher age has been consistently associated with increased rates of fatal drug anaphylaxis. This may be related to an increased prevalence of drug allergy following an increased drug exposure, and/or to an increased underlying cardiovascular vulnerability. 33

FIGURE 1.

FIGURE 1

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Hospitalizations and intensive care units in older people (from 30 ). Grades of anaphylaxis according to Ring and Messner. Old age people: N = 1123, adults: N = 5768. ***: p < 0.001. In this study, hospitalization and ICU were differentiated between adults and old age people

TABLE 1.

Symptoms and anaphylaxis grades (from Ring and Messmer 32 , 52 )

Grades Skin Abdomen Airways Cardiovascular system
I

Itch

Flush

Urticaria

Angioedema
II

Nausea

Cramps

Rhinorrhea

Hoarseness

Dyspnea

Tachycardia (>120/min)

Hypotension (<90 mm Hg syst)

Arrythmia
III

Vomiting

Defecation

Laryngeal edema Bronchospasm

Cyanosis

 Shock
IV Respiratory arrest Cardiac arrest
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Anaphylaxis is usually graded according to Ring and Messmer 32 (Table 1), although there are proposals for new grading systems. 34 , 35 However, WHO and regulatory authorities recommend the use of the Brighton Collaboration Anaphylaxis Working Group for pharmacovigilance registers. 23

Classification according to the most severe symptom is mandatory.

4. RISK FACTORS FOR SEVERITY OF ANAPHYLAXIS IN OLDER PEOPLE

4.1. Comorbidity

In the European Anaphylaxis Registry, older age (excluding the confounding factor of concomitant cardiovascular or other diseases) and concomitant mastocytosis 36 were the most important predictors for an increased risk of severe anaphylaxis. 30 , 37 , 38 , 39 Hereditary alpha‐tryptasemia is another risk factor. Anaphylaxis is more severe and has an increased risk of death in patients with coronary artery disease because both the number of mast cells and the production of their vasoactive mediators are increased in ischemic cardiomyopathy. In addition, atherosclerotic lesions make coronary arteries more susceptible to the effects of mast cell‐ and basophil‐derived mediators, 40 and individuals with an underlying vascular illness less tolerant to hypoxia and hypotension during anaphylaxis.

In older people from the registry, cardiovascular diseases, thyroid diseases, and cancer were more common than in younger adults. 37

4.2. Polypharmacy and medications used in older people

In the European Anaphylaxis Registry, medications associated with an increased risk of severe anaphylaxis risk cofactors—such as ACE inhibitors (angiotensin‐converting enzyme inhibitor), AT‐2‐antagonists (Angiotensin II receptor type 2), ß‐blockers, acetylcholine, and proton pump inhibitors—were significantly more frequently prescribed in older people (57%) than in younger adults (18%). 38

Independent of the age of the patient, ß‐blockers and ACE inhibitors administered close to allergen immunotherapy increased the risk of developing severe anaphylaxis, while aspirin and AT‐2 did not. 38 However, a systematic review with low‐quality evidence showed that ß‐blockers and ACE inhibitors increased the severity of anaphylaxis, due to differences in confounders, in particular, cardiovascular diseases. 41

It is important to highlight the significant number of older patients who are being treated with anxiolytics, antidepressants, hypnotics, and other drugs that can act on the central nervous system and alter the individual person's recognition and perception of the symptoms and signs of anaphylaxis.

5. MANAGEMENT OF ANAPHYLAXIS IN OLDER PEOPLE

5.1. The ABCDE approach

The Airway, Breathing, Circulation, Disability, Exposure (ABCDE) algorithm is applicable in all clinical emergencies for immediate assessment and treatment 42 (Figure 2). If anaphylaxis is suspected, every patient should receive rapid evaluation of vital functions via ABCDE, and problems should be addressed in a targeted manner.

FIGURE 2.

FIGURE 2

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The ABCDE approach in emergencies (from 42 )

The aims of the ABCDE approach are 42 :

  • To provide life‐saving treatment.

  • To break down complex clinical situations into more manageable parts.

  • To serve as an assessment and treatment algorithm.

  • To establish common situational awareness among all treatment providers.

  • To buy time to establish a final diagnosis and treatment.

5.2. Adrenaline in older people

Guidelines from EAACI 43 and the World Allergy Organization 44 recommend prompt intramuscular injection of adrenaline as first‐line therapy for anaphylaxis. Adrenaline can counteract most severe symptoms of anaphylaxis in older people. 22 Intramuscular administration of adrenaline, if possible using a ready‐to‐use preparation or auto‐injector, is recommended. The initial dose is 0.3–0.5 ml of a 1:1000 dilution (1 mg/ml). The patient should then be monitored, and, if ineffective, the administration can be repeated after at least a 5‐minute interval. 22 The subcutaneous route should not be used because the vasoconstrictor effect of adrenaline injected into the subcutaneous tissue potentially delays adrenaline absorption. 45 The intra‐vascular route should be avoided since most cardiovascular adverse events of adrenaline appear to occur via this route. 46 Intravenous continuous infusion should only be given to patients not responding to intramuscular injection under careful ECG monitoring. 43

During an anaphylactic reaction occurring in patients with cardiovascular disease, the benefits versus the harms of adrenaline injection should be weighed carefully. The presence of cardiovascular disease does not exclude the use of adrenaline in anaphylaxis since no other medications have life‐saving effects in this medical emergency. 40 There are no absolute contraindications to the prescription of self‐injectable adrenaline in older patients or in those with a cardiovascular disease who are at risk of anaphylaxis. Serious adverse effects, such as ventricular arrhythmias, hypertension, or myocardial ischemia, have not been reported following the use of adrenaline auto‐injectors. 47 However, older patients with anaphylaxis seem to be more likely to experience a cardiac adverse event after adrenaline injection, with those older than 80 years having the highest risk. 48

5.3. Other treatments

Regular intake of multiple medications is frequent in older patients (polypharmacy). Co‐medication may modify the evolution of anaphylaxis, and also its management. The therapeutic effect of adrenaline may be blunted by ß‐blockers. In this situation, if epinephrine is not effective, glucagon can be administered intravenously, as it has a mechanism of action independent of the ß‐receptors. 49 , 50 Older patients may be using sedating or psychotropic drugs, and these could affect the recognition and perception of anaphylactic symptoms. 51

5.4. Equipment needed to perform vaccination safely in older people

  • Vaccination should always be performed in a healthcare setting, which may be a mobile unit.

  • All necessary aids and rescue drugs must be available in the vaccination setting.

  • All medical personnel assigned should receive training and be able to immediately recognize and manage an emergency situation, including anaphylaxis.

6. PRACTICAL PREVENTION AND MANAGEMENT OF AN ANAPHYLACTIC REACTION

As proposed in three ARIA‐EAACI Position Papers on anaphylaxis to COVID‐19 vaccines, recommendations have been adapted for older patients. 21 , 28 , 29

  • Patients with a history of allergic diseases should not be excluded from the vaccines as the exclusion of all these patients from vaccination may have a significant impact on reaching the goal of herd immunity. However, without any allergist advice, a previously known allergy to the substances contained in the vaccines presents a contraindication, as well as a reaction to the first dose of the COVID‐19 vaccine, which presents a contraindication for administering the second dose. A previous severe anaphylactic reaction to other vaccines or drugs does not represent a contraindication. However, consultation with an allergist may be helpful to assess the individual situation.

  • Healthcare practitioners vaccinating against COVID‐19 are required to be sufficiently prepared to recognize and treat anaphylaxis properly, particularly since older patients tend to have more severe anaphylactic symptoms. If a severe reaction occurs, hospitalization may be considered more readily than for younger adults after first‐aid action.

  • After vaccine administration, a mandatory observation period of at least 15 minutes is necessary for all individuals. This should include the possibility to administer adrenaline intra‐muscularly (IM) in a sufficient dose. The observation period should be extended to 30 minutes for patients deemed at putative risk for anaphylactic reaction.

  • The person injecting the vaccine should be capable of managing an anaphylaxis reaction at first instance and should have all the relevant medication for management readily available.

  • In the case of COVID‐19 vaccines, there will be new procedures outside of the medical setting. Thus, it is imperative that the relevant emergency medication (adrenaline and saline) is readily available at the setting—particularly in nursing homes or vaccine caravans—and that training of the personnel has been accomplished.

  • The EAACI recently published the practical management of anaphylaxis (Figure 3). 29

FIGURE 3.

FIGURE 3

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Diagnosis and management of severe allergic reactions after COVID‐19 vaccination in the vaccination center (from 29 )

CONFLICT OF INTEREST

IA reports is Associate Editor Allergy and CTA. JB reports personal fees from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi‐Aventis, Takeda, Teva, Uriach, other from KYomed‐Innov, personal fees from Purina. VC reports personal fees from ALK, Allergy Therapeutics, LETI, Thermo Fisher, Merck, Astrazeneca, GSK. AC reports personal fees from BMS, MSD. ME reports personal fees from DBV Technologies, Mylan. MFR reports grants from ISCII (Spanish Government), Aimmune, Diater, personal fees from Aimmune, DBV, Novartis, SPRIM, ALK, Allergy Therapeutics, Diater, GSK, Thermo Fisher. BG reports grants from Astrazeneca, Novartis, MSD, Deva, Abdi Ibrahim, GSK. TH reports personal fees from GSK, Mundipharma, OrionPharma, Sanofi. LK reports grants and personal fees from Allergopharma, LETI Pharma, MEDA/Mylan, Sanofi, personal fees from HAL Allergie, Allergy Therapeut., Cassella med, grants from ALK Abelló, Stallergenes, Quintiles ASIT biotech, Lofarma, AstraZeneca, GSK, Inmunotk, and Membership: AeDA, DGHNO, Deutsche Akademie fürAllergologie und klinischeImmunologie, HNO‐BV, GPA, EAACI. PK reports personal fees from Adamed, AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Hal Allergy, Lekam, Mylan, GSK, Novartis, Polpharma, Sanofi, from Teva. VK reports non‐financial support from AstraZeneca, DIMUNA, BerlinCHemieMenarini Baltic. RL reports grants from Astra Zeneca, Chiesi, GSK, other from Astra Zeneca, Novartis, GSK, Sanofi. JM reports personal fees and other from SANOFI GENZYME & REGENERON, NOVARTIS, ALLAKOS, grants and personal fees from MYLAN Pharma, URIACH Group, personal fees from Mitsubishi‐Tanabe, Menarini, UCB, AstraZeneca, GSK, MSD. MO reports grants from Astra Zeneca, Chiesi, GSK, DBV Technologies, Aimmune, Novartis, Pfizer, Regeneron, Sanofi, Boehringer Ingelheim; and volunteer President of the European Federation of Allergy and Airways Diseases Patients’ Associations EFA who receives unrestricted grants from pharmaceutical companies. Second Vice President of the Swedish Asthma and Allergy Association, who receives no income from companies. Takes part in Novartis Asthma Patient Advisory Committee, GSK Global Respiratory Patient Advisory Group and have participated/presented in AstraZeneca events. Whenever there was a honorarium, this went to EFA. OP reports research grants from Inmunotek S.L., Novartis, and MINECO. fees for giving scientific lectures or participation in Advisory Boards from Allergy Therapeutics, Amgen, AstraZeneca, Diater, GlaxoSmithKline, S.A, Inmunotek S.L, Novartis, Sanofi Genzyme and Stallergenes. NP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, BencardAllergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., rom Laboratorios LETI/LETI Pharma, Anergis S.A., Glaxo Smith Kline, personal fees from Astellas Pharma Global, MEDA Pharma/MYLAN, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis, and Sanofi Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS, Paul‐Martini‐Stiftung (PMS), Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies grants from Pohl‐Boskamp, Inmunotek S.L., Biomay, Circassia. DP reports grants and personal fees from GlaxoSmithKline, personal fees and non‐financial support from Boehringer Ingelheim, personal fees from Belupo, AbbVie, MSD, Chiesi, Menarini, Pliva, Revenio, non‐financial support from Philips. YR reports grants from BIOPHYTIS, NOVARTIS. BS reports personal fees from Allergopharma, Viatris, TEVA, ADAMED, patient ombudsman, Polish Allergology Society grants from AstraZeneca, National Health Programm, grant and personal fees from Polpharma, AstraZeneca. AS reports grants and personal fees from Medical Research Council, Thermo Fisher, Buhlmann, Infomed, Nutricia and Nestle, Allergy Therapeutics, Novartis and Stallergenes, grants from Food Allergy Research and Education, Asthma UK, NIAID / Immune Tolerance Network, non‐financial support from National Institute for Health Research, Thermo Fisher and Buhlmann. Dr. Serpa reports personal fees from Takeda, personal fees and other from Novartis, personal fees from Sanofi, personal fees from GSK, other from Astra Zeneca. JS reports grants and personal fees from SANOFI, personal fees from GSK, NOVARTIS, ASTRA ZENECA, MUNDIPHARMA, FAES FARMA. AS reports grants from HDRUK. MS reports grants from Swiss National Science Foundation (SNF), GlaxoSmithKline (GSK). RS reports grants from São Paulo Research Foundation, MSD, grants and personal fees from Novartis, grants, personal fees and non‐financial support from AstraZeneca, grants, personal fees and non‐financial support from Chiesi, personal fees and non‐financial support from Boehringer Ingelheim. GS reports grants and personal fees from ALK‐Abello, personal fees from Novartis, Bencard, Stallergens, HAL, Allergopharma, Mylan. AMTB reports grants and personal fees from Teva, AstraZeneca, GSK (GlaxoSmithKline), Sanofi, Mundipharma, personal fees from Bial, grants from Leti, Novartis. STS reports personal fees from AstraZeneca, ERT, Novartis, Sanofi Pharma, Roche Products, grants from GSK. MT reports grants from European Commission, SEAIC, ISCIII, personal fees from Diater laboratory, Leti laboratory, Aimmune Therapeutics. IT reports personal fees from Honoraria for educational activities, speaking engagements, advisory boards from Boehringer Ingelheim, Astra Zeneca, GSK, Novartis and grants from GSK Hellas and Elpen. CSU reports personal fees from Astra Zeneca, personal fees from Chiesi, grants and personal fees from Novartis, Boehringer Ingelheim, personal fees from ALK‐Abello, TEVA, Orion Pharma, grants Sanofi Genzyme, personal fees and non‐financial support from GSK. IV reports personal fees from Novartis, Sanofi, personal fees and non‐financial support from Thermo Fisher, non‐financial support from Beckman Coulter. DW reports other from Kaleo, Mylan, and on the AAAAI/ACAAI Joint Task Force on Practice Parameters updating the Anaphylaxis practice parameter. SW reports other from Pfizer, Kaleo, Bausch Lomb. MW reports other from Regeneron Pharmaceuticals, DBV Technologies S.A, Stallergenes GmbH, HAL Allergie GmbH, BencardAllergie GmbH, Allergopharma GmbH & Co. KG, ALK‐AbellóArzneimittel GmbH, Mylan Germany GmbH, Leo Pharma GmbH, Sanofi‐Aventis Deutschland GmbH, Aimmune Therapeutics UK Limited, Actelion Pharmaceuticals Deutschland GmbH, Novartis AG, Biotest AG, AbbVie Deutschland GmbH & Co. KG, Lilly Deutschland GmbH. TZ reports and Organizational affiliations: Committee member: WHO‐Initiative "Allergic Rhinitis and Its Impact on Asthma" (ARIA), Member of the Board: German Society for Allergy and Clinical Immunology (DGAKI), Board Chairman: European Centre for Allergy Research Foundation (ECARF). President: Global Allergy and Asthma European Network (GA2LEN), Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO).

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