Bibliografisk note

Funding Information:
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 (GALEN), Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). 2

Funding Information:
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 Abell?, Stallergenes, Quintiles ASIT biotech, Lofarma, AstraZeneca, GSK, Inmunotk, and Membership: AeDA, DGHNO, Deutsche Akademie f?rAllergologie 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-Abell?, 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 S?o 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-Abell?Arzneimittel 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). 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 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 care32 (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 Itch Flush Urticaria Angioedema Nausea Cramps Rhinorrhea Hoarseness Dyspnea Tachycardia (>120/min) Hypotension (<90?mm Hg syst) Arrythmia Vomiting Defecation Laryngeal edema Bronchospasm Cyanosis Anaphylaxis is usually graded according to Ring and Messmer32 (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. 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.6-9 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,12-16 and recommendations to control COVID-19 in these settings have been issued.16-18 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.19-21 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.

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© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.