Immediate Hypersensitivity Reactions Induced by COVID-19 Vaccines: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Vivi Li and Version 1 by Shuen-Iu Hung.

As the world deals with the COVID-19 pandemic, vaccination remains vital to successfully end this crisis. However, COVID-19-vaccine-induced immediate hypersensitivity reactions presenting with potentially life-threatening systemic anaphylactic reactions are one of the reasons for vaccine hesitancy. Recent sStudies have suggested that different mechanisms, including IgE-mediated and non-IgE-mediated mast cell activation, may be involved in immediate hypersensitivity. The main culprits triggering hypersensitivity reactions have been suggested to be the excipients of vaccines, including polyethylene glycol and polysorbate 80. Patients with a history of allergic reactions to drugs, foods, or other vaccines may have an increased risk of hypersensitivity reactions to COVID-19 vaccines. Various strategies have been suggested to prevent hypersensitivity reactions, including performing skin tests or in vitro tests before vaccination, administering different vaccines for the primary and following boosters, changing the fractionated doses, or pretreating the anti-IgE antibody.

  • COVID-19 vaccines
  • IgE-mediated pathway
  • immediate hypersensitivity reactions
  • skin test

1. Introduction

Since its discovery, coronavirus disease 2019 (COVID-19) has remained a global public health pandemic [1]. With the announcement of its genetic sequence, researchers and companies have raced to develop vaccines to end the pandemic. The administration of vaccines has successfully reduced the morbidity and mortality of COVID-19 [2,3,4,5][2][3][4][5]. According to the World Health Organization [6], the increasing availability and utilization of vaccines effectively protects people from the disease severity [7,8,9][7][8][9]. Currently, four classes of vaccines against COVID-19 are available. (1) mRNA vaccines use an innovative approach for inducing messenger RNA (mRNA) molecules to safely produce COVID-19 proteins, resulting in an immune response. (2) Viral vector vaccines use genetically engineered viral vectors to produce COVID-19 proteins to stimulate the host’s immunity. (3) Inactivated virus vaccines use a weakened state of the COVID-19 virus that the host is capable of mounting an immune response against. (4) Protein subunit vaccines use COVID-19 protein fragments as a stimulus to trigger immune responses [10].

2. Clinical Phenotypes of Vaccine-Induced Immediate Hypersensitivity Reactions

Although vaccination has dramatically improved the control of COVID-19 transmission [11], vaccination hesitancy remains a significant issue owing to adverse reactions, particularly unpredictable hypersensitivity reactions [12,13][12][13]. Most hypersensitivity reactions to vaccines occur immediately and abruptly within minutes to hours after administration [14,15,16][14][15][16]. The clinical manifestations may range from mild cutaneous eruptions, such as urticaria or angioedema, to life-threatening systemic anaphylaxis [17]. Urticaria is characterized by transient wheal formation and may produce an itching or burning sensation. Angioedema is characterized by painful swelling in the deep dermis and subcutis layers of the skin. Both presentations are part of a spectrum of systemic symptoms, including anaphylaxis [18]. Anaphylaxis is rare but frequently leads to death [19,20][19][20]. Most immediate hypersensitivity reactions have occurred after administrating the first dose. However, reactions after the second dose of the COVID-19 vaccine have also been reported [21]. Approximately 86% of anaphylaxis cases induced by COVID-19 vaccines occur within 30 min of inoculation. On the contrary, the onset of other symptoms, such as urticaria, often happens within 3–8 days of the first dose and 2–5 days after the second dose [21,22,23][21][22][23]. Many vaccine-induced hypersensitivity reactions could not be confirmed and have been attributed post factum to alternative diagnoses, such as vasovagal syncope, vocal cord dysfunction, exacerbation of existing chronic spontaneous urticaria, and anxiety. Using an updated global standard for case definitions and guidelines for hypersensitivity reactions following vaccinations may help with clinical differential diagnosis and management [24,25][24][25].

3. Epidemiology of Immediate Hypersensitivity Induced by Vaccines

Vaccine-induced anaphylaxis cases are estimated to occur in approximately 1 case per 15 million to 2 cases per million individuals [14]. Micheletti F. et al. reported that the risk of anaphylaxis after vaccination in children and adults was estimated to be 1.31 (95% confidence interval [CI], 0.90~1.84) per million doses before the COVID-19 pandemic [26]. The authors identified 33 confirmed vaccine-triggered anaphylaxis cases in the study after 25,173,965 vaccine doses [26]. Among the patients with vaccine-induced immediate hypersensitivity reactions, approximately 66% had urticaria, and 10% had angioedema [27]. For COVID-19 vaccines, cutaneous reactions were reported by 1.9% of individuals after receiving the first dose of an mRNA COVID-19 vaccine. Approximately 2.3% of those who had no adverse events following the first dose developed hypersensitivity reactions after receiving the second dose [28]. Based on a U.S. study, cutaneous reactions induced by the mRNA COVID-19 vaccines were more common in women than in men (85% vs. 15%, p < 0.001) [28]. Furthermore, the estimated incidence rates for anaphylaxis in the U.S. were 11.1 cases per million doses administered with the BNT162b2 (Pfizer-BioNTech) vaccine and 2.5 cases per million doses administered with the mRNA-1273 (Moderna) vaccine [16,29,30,31][16][29][30][31]. The vaccine adverse event reporting system (VAERS) [32] showed that there were 1592 urticaria cases among 15703 (10.13%) cases with adverse reactions, 32 (4.92%) out of 650 adverse event cases of angioedema, and 66 (3.54%) out of 1867 adverse event cases of anaphylaxis from 2020 to January 2022 attributed to COVID-19 vaccines. A recent meta-analysis study suggested that the estimated incidence of COVID-19-vaccine-induced anaphylaxis ranged from 2.5 to 7067 per one million individuals receiving mRNA COVID-19 vaccines, with an overall pooled prevalence estimate of 5.58 (95% CI, 3.04–8.12; I2  =  76.32%, p < 0.01) [21]. In contrast, the incidences of nonanaphylactic reactions to mRNA COVID-19 vaccines ranged from 10.6 to 472,973 per one million, with an overall pooled prevalence estimate of 89.53 (95% CI, 11.87–190.94; I2  =  97.08%, p < 0.01) [21]. Chu, DK. et al. performed a meta-analysis of 22 studies, including 1366 patients, and found a low incidence (0.16%) of immediate severe allergic reactions associated with the second dose of the mRNA COVID-19 vaccine among individuals who had an allergic history of their first dose [33]. In a separate study, the incidence rates of anaphylaxis were lower for the viral COVID-19 vaccine (odds ratio [OR], 0.47; 95% CI, 0.33–0.68) and the inactivated COVID-19 (OR, 0.31; 95% CI, 0.18–0.53) vaccine [34]. Different setups of studies may observe different incidence rates. Table 1 lists the incidence rates of anaphylactic and nonanaphylactic hypersensitivity reactions to COVID-19 vaccines.
Table 1.
 Incidence rates of anaphylactic and nonanaphylactic hypersensitivity reactions to COVID-19 vaccines.
Type of Reaction Number of Participants Number of Anaphylactic Reactions Type of Vaccine Incidence of Reactions (per One Million) Reference
anaphylactic          
  890,604 15 mRNA-1273; BNT162b2 17 [35]
  4,041,396 10 mRNA-1273 37.1 [29]
  1,893,360 21 BNT162b2 11 [36]
  1116 1 BNT162b2; mRNA-1273 890 [37]
  283 5 mRNA-1273 and AZD1222 17,668 [38]
nonanaphylactic          
  277 14 BNT162b2 50,540 [39]
  5589 1391 AZD1222

(Astra Zeneca)		 248,880 [39]
  5574 6 BNT162b2 1070 [40]
  3170 11 BNT162b2 3470 * [41]
  1,893,360 83 BNT162b2 43.8 * [36]
  877 10 BNT162b2 11,400 [42]
  1116 7 BNT162b2; mRNA-1273 6270 [37]
  74 35 BNT162b2 472,973 [23]
* Nonanaphylactic reactions were classified under skin rashes, including hives, pruritus, and eczematous papules.
The available information suggests that the incident rate of adverse events after the administration of the protein-based vaccine (Nuvaxovid/NVX-CoV2373 produced by Novavax, Gaithersburg, MD, USA) is lower than the mRNA vaccines [43,44,45][43][44][45]. Almost all the reported incidences of vaccine-induced adverse reactions come from passive reporting systems (such as VAERS), which may underestimate the true burden [46]. In addition, limited prospective studies have been performed, which could result in a much higher rate of acute allergic reactions, possibly due to a nocebo effect [47].

4. Causality of Vaccine-Induced Immediate Hypersensitivity Reactions

Vaccine excipients and active components could cause allergens to elicit hypersensitivity reactions. These antigen components, such as toxoids or constituents of pneumococcal vaccines, cause symptoms ranging from urticaria to anaphylaxis. Hypersensitivity reactions may be induced when patients receive the first or the second dose of a vaccine [48,49][48][49]. Vaccine excipients are known to be ingredients other than the active components of vaccines. These are inactive ingredients that stabilize or preserve the viability of the vaccines and maintain their bioavailability. Egg and ovalbumin (a residual component of egg processing) are considered the most frequent food allergies in children and the most suspected culprits for allergies induced by the administration of traditional vaccines [49,50,51,52][49][50][51][52]. Gelatin is another culprit excipient for vaccine-induced immediate hypersensitivity reactions [51,52,53][51][52][53]. Vaccine adjuvants are also possible allergens [54]. Aluminum hydroxide and aluminum phosphate are adjuvants that are more commonly found in vaccines but are not in the COVID-19 vaccine. Although rare, they are commonly associated with delayed-type hypersensitivity reactions. Aluminum can also induce immediate-type hypersensitivity by stimulating mast cells and other immune cells [49,55][49][55]. Another vaccine adjuvant, AS03, is a squalene derivative that is incorporated into influenza vaccines. Epidemiological studies in Canada have shown an approximately 20-fold increase in the incidence of immediate hypersensitivity using AS03-adjuvanted vaccines compared with non-AS03 vaccines. The immune mechanism underlying vaccine-adjuvant-induced immediate hypersensitivity reactions remains unclear [49,54,56,57][49][54][56][57].

5. Proposed Immune Mechanisms for Vaccine-Induced Immediate Hypersensitivity Reactions

According to cellular and molecular features defined by Gell and Coomb, there are four types of hypersensitivity reactions: I, II, III, and IV [58]. Type I hypersensitivity reactions involve IgE-mediated immune responses and occur rapidly after exposure to allergens. Type II hypersensitivity is mediated by IgG or IgM antibodies, and type III hypersensitivity involves the immune complexes. Type IV hypersensitivity is mediated by T lymphocytes, also known as delayed-type reactions. Mast cells are considered the most critical immune cells responsible for immediate hypersensitivity reactions, as they secrete various inflammatory cytokines and induce various systemic immune responses [52]. There are four proposed mechanisms for immediate hypersensitivity reactions, including (1) immunoglobulin E (IgE)-mediated, (2) complement-receptor-mediated, (3) MRGPRX2 (Mas-related G-protein coupled receptor member X2)-mediated mast cell direct activation, and (4) an unknown mechanism (Figure 1).
Figure 1. Proposed mechanismsfor immediate hypersensitivity reactions. There are four proposed mechanisms for immediate hypersensitivity: IgE-mediated, complement-receptor-mediated, Mas-related G protein-coupled receptor X2 (MRGPRX2)-mediated mast cell activation, and an unknown mechanism. Binding of allergens from the components of vaccines to antibodies or receptors may initiate the hypersensitivity reactions. The specific IgE antibodies recognize the active components or excipients of the vaccines. IgE antibodies are then coupled with receptor-FcεRI on the mast cells, resulting in mast cell degranulation. These specific IgE antibodies may be brought by previous exposure to allergens in cosmetics, drugs, aeroallergens, or food. Vaccine components may activate the complement-receptor-mediated pathway and induce anaphylatoxins that could be recognized by complement receptors on the mast cells. In addition, binding of the vaccine components and excipients to MRGPRX2 receptor may directly activate mast cells. Furthermore, immediate hypersensitivity reactions may be induced by an unknown mechanism. These proposed mechanisms could lead to mast cell degranulation and the release of effector mediators. Abbreviation: MRGPRX2, Mas-related G protein-coupled receptor X2; IgE, immunoglobulin E; PEG, polyethylene glycol.
The IgE-dependent pathway is the most common and well-known mechanism [52]. In IgE-mediated hypersensitivity reactions, a foreign allergen(s) is proposed to be recognized by IgE, which binds to its receptor Fc epsilon RI (FcεRI) on mast cells, thereby activating the mast cells and releasing highly active immune mediators [59] (Figure 1). The reactions often occur within minutes of the crosslinking of IgE to FcεRI receptors. Subsequently, the mediators secreted by mast cells can induce a late-phase reaction, usually 2–6 h after initiation, with a peak in activity after 6–9 h [60]. The second proposed mechanism, “the complement-receptor-mediated hypersensitivity,” can be initiated by the binding of allergens in vaccines and IgG or IgM and then activate the complement system to produce anaphylatoxins (e.g., C3a, C4a, and C5a) (Figure 1). These complement peptides can bind to complement receptors on mast cells, and then mast cell degranulation results in the release of immune mediators. In contrast to the IgE-dependent pathway, this proposed mechanism of hypersensitivity reaction does not involve IgE antibodies against allergens [61,62][61][62]. Third, several studies have suggested that the binding of allergens to MRGPRX2 (the mastocyte-related G-protein coupled receptor X2) protein, a class of G-protein-coupled receptors expressed on mast cells, may directly trigger mast cell activation and participate in non-IgE-mediated reactions [63] (Figure 1). It has been found that many molecules, such as antimicrobial host defense peptides, neuropeptides, and cationic amphiphilic drugs, could be the allergens for the induction [64]. However, no convincing evidence has demonstrated that MRGPRX2 or complements are involved in COVID-19-vaccine-induced immediate hypersensitivity reactions. An unknown mechanism may be involved in immediate hypersensitivity reactions induced by COVID-19 vaccines, which could trigger mast cell degranulation or other immune cell activations (Figure 1). Many of the immediate hypersensitivity reactions are considered IgE-mediated, supported by skin prick tests and specific IgE levels [65]. Several excipients have been suggested to trigger the production of specific IgE antibodies and cause mast cell activation [65]. Patients with specific IgE antibodies against vaccine antigens may have higher risks of hypersensitivity reactions [66]. Several studies have attributed the development of hypersensitivity to increased specific IgE levels towards vaccine antigens. However, increased IgE levels may be a false-positive result in atopic individuals [48,67,68][48][67][68]. It is proposed that both IgE-mediated and non-IgE mediated pathways are involved in vaccine-induced immediate hypersensitivity reactions. Further studies are needed to investigate the mechanisms of COVID-19-vaccine-induced immediate hypersensitivity reactions.

References

  1. Etienne, C.F. COVID-19 has revealed a pandemic of inequality. Nat. Med. 2022, 28, 17.
  2. Graham, F. Daily briefing: COVID-19 vaccine development—Where we are now. Nature 2020. Online ahead of print.
  3. Sahin, U.; Muik, A.; Derhovanessian, E.; Vogler, I.; Kranz, L.M.; Vormehr, M.; Baum, A.; Pascal, K.; Quandt, J.; Maurus, D.; et al. Publisher correction: COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 2021, 590, E17.
  4. Arunachalam, P.S.; Walls, A.C.; Golden, N.; Atyeo, C.; Fischinger, S.; Li, C.; Aye, P.; Navarro, M.J.; Lai, L.; Edara, V.V.; et al. Adjuvanting a subunit COVID-19 vaccine to induce protective immunity. Nature 2021, 594, 253–258.
  5. Heitmann, J.S.; Bilich, T.; Tandler, C.; Nelde, A.; Maringer, Y.; Marconato, M.; Reusch, J.; Jager, S.; Denk, M.; Richter, M.; et al. A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity. Nature 2022, 601, 617–622.
  6. Cui, X.; Wang, P.; Wei, Z. Emergency use of COVID-19 vaccines recommended by the World Health Organization (WHO) as of June 2021. Drug Discov. Ther. 2021, 15, 222–224.
  7. Baden, L.R.; El Sahly, H.M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.; Creech, C.B.; et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 2021, 384, 403–416.
  8. Ali, K.; Berman, G.; Zhou, H.; Deng, W.; Faughnan, V.; Coronado-Voges, M.; Ding, B.; Dooley, J.; Girard, B.; Hillebrand, W.; et al. Evaluation of mRNA-1273 SARS-CoV-2 vaccine in adolescents. N. Engl. J. Med. 2021, 385, 2241–2251.
  9. Walter, E.B.; Talaat, K.R.; Sabharwal, C.; Gurtman, A.; Lockhart, S.; Paulsen, G.C.; Barnett, E.D.; Munoz, F.M.; Maldonado, Y.; Pahud, B.A.; et al. Evaluation of the BNT162b2 COVID-19 Vaccine in Children 5 to 11 Years of Age. N. Engl. J. Med. 2022, 386, 35–46.
  10. Mascellino, M.T.; Di Timoteo, F.; De Angelis, M.; Oliva, A. Overview of the main anti-SARS-CoV-2 vaccines: Mechanism of action, efficacy and safety. Infect. Drug Resist. 2021, 14, 3459–3476.
  11. Storlie, C.B.; Pollock, B.D.; Rojas, R.L.; Demuth, G.O.; Johnson, P.W.; Wilson, P.M.; Heinzen, E.P.; Liu, H.; Carter, R.E.; Habermann, E.B.; et al. Quantifying the importance of COVID-19 vaccination to our future outlook. Mayo. Clin. Proc. 2021, 96, 1890–1895.
  12. Abrams, E.M.; Shaker, M.; Sinha, I.; Greenhawt, M. COVID-19 vaccines: Addressing hesitancy in young people with allergies. Lancet. Respir. Med. 2021, 9, 1090–1092.
  13. Digregorio, M.; Van Ngoc, P.; Delogne, S.; Meyers, E.; Deschepper, E.; Duysburgh, E.; De Rop, L.; De Burghgraeve, T.; Coen, A.; De Clercq, N.; et al. Vaccine hesitancy towards the COVID-19 vaccine in a random national sample of belgian nursing home staff members. Vaccines 2022, 10, 598.
  14. Nilsson, L.; Brockow, K.; Alm, J.; Cardona, V.; Caubet, J.C.; Gomes, E.; Jenmalm, M.C.; Lau, S.; Netterlid, E.; Schwarze, J.; et al. Vaccination and allergy: EAACI position paper, practical aspects. Pediatr. Allergy Immunol. 2017, 28, 628–640.
  15. Castells, M.C.; Phillips, E.J. Maintaining safety with SARS-CoV-2 vaccines. N. Engl. J. Med. 2021, 384, 643–649.
  16. Shimabukuro, T.; Nair, N. Allergic reactions including anaphylaxis after receipt of the first dose of pfizer-BioNTech COVID-19 vaccine. JAMA 2021, 325, 780–781.
  17. Dreskin, S.C.; Halsey, N.A.; Kelso, J.M.; Wood, R.A.; Hummell, D.S.; Edwards, K.M.; Caubet, J.C.; Engler, R.J.; Gold, M.S.; Ponvert, C.; et al. International consensus (ICON): Allergic reactions to vaccines. World Allergy Organ. J. 2016, 9, 32.
  18. Zuberbier, T.; Abdul Latiff, A.H.; Abuzakouk, M.; Aquilina, S.; Asero, R.; Baker, D.; Ballmer-Weber, B.; Bangert, C.; Ben-Shoshan, M.; Bernstein, J.A.; et al. The international EAACI/GA(2)LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy 2021, 77, 734–766.
  19. Cheng, D.R.; Perrett, K.P.; Choo, S.; Danchin, M.; Buttery, J.P.; Crawford, N.W. Pediatric anaphylactic adverse events following immunization in Victoria, Australia from 2007 to 2013. Vaccine 2015, 33, 1602–1607.
  20. Poziomkowska-Gesicka, I.; Kurek, M. Clinical manifestations and causes of anaphylaxis. analysis of 382 cases from the anaphylaxis registry in west Pomerania Province in Poland. Int. J. Environ. Res. Public Health 2020, 17, 109.
  21. Alhumaid, S.; Al Mutair, A.; Al Alawi, Z.; Rabaan, A.A.; Tirupathi, R.; Alomari, M.A.; Alshakhes, A.S.; Alshawi, A.M.; Ahmed, G.Y.; Almusabeh, H.M.; et al. Anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines: A systematic review and meta-analysis. Allergy Asthma Clin. Immunol. 2021, 17, 109.
  22. Cabanillas, B.; Novak, N. Allergy to COVID-19 vaccines: A current update. Allergol. Int. 2021, 70, 313–318.
  23. McMahon, D.E.; Amerson, E.; Rosenbach, M.; Lipoff, J.B.; Moustafa, D.; Tyagi, A.; Desai, S.R.; French, L.E.; Lim, H.W.; Thiers, B.H.; et al. Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases. J. Am. Acad. Dermatol. 2021, 85, 46–55.
  24. Kohl, K.S.; Bonhoeffer, J.; Braun, M.M.; Chen, R.T.; Duclos, P.; Heijbel, H.; Heininger, U.; Loupi, E.; Marcy, S.M. The brighton collaboration: Creating a global standard for case definitions (and guidelines) for adverse events following immunization. In Advances in Patient Safety: From Research to Implementation; Henriksen, K., Battles, J.B., Marks, E.S., Lewin, D.I., Eds.; Agency for Healthcare Research and Quality: Rockville, MD, USA, 2005; Volume 2.
  25. Laisuan, W. COVID-19 vaccine anaphylaxis: Current evidence and future approaches. Front Allergy 2021, 2, 801322.
  26. McNeil, M.M.; Weintraub, E.S.; Duffy, J.; Sukumaran, L.; Jacobsen, S.J.; Klein, N.P.; Hambidge, S.J.; Lee, G.M.; Jackson, L.A.; Irving, S.A.; et al. Risk of anaphylaxis after vaccination in children and adults. J. Allergy Clin. Immunol. 2016, 137, 868–878.
  27. Micheletti, F.; Peroni, D.; Piacentini, G.; Schweiger, V.; Mirandola, R.; Chiesa, E.; Zanoni, G. Vaccine allergy evaluation and management at the specialized green channel consultation clinic. Clin. Exp. Allergy 2012, 42, 1088–1096.
  28. Robinson, L.B.; Fu, X.; Hashimoto, D.; Wickner, P.; Shenoy, E.S.; Landman, A.B.; Blumenthal, K.G. Incidence of cutaneous reactions after messenger RNA COVID-19 vaccines. JAMA Dermatol 2021, 157, 1000–1002.
  29. Shimabukuro, T. Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine—United States, December 21, 2020-January 10, 2021. Am. J. Transplant. 2021, 21, 1326–1331.
  30. Shimabukuro, T. Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine—United States, December 14–23, 2020. Am. J. Transplant. 2021, 21, 1332–1337.
  31. Sampath, V.; Rabinowitz, G.; Shah, M.; Jain, S.; Diamant, Z.; Jesenak, M.; Rabin, R.; Vieths, S.; Agache, I.; Akdis, M.; et al. Vaccines and allergic reactions: The past, the current COVID-19 pandemic, and future perspectives. Allergy 2021, 76, 1640–1660.
  32. Pool, V.; Braun, M.M.; Kelso, J.M.; Mootrey, G.; Chen, R.T.; Yunginger, J.W.; Jacobson, R.M.; Gargiullo, P.M.; VAERS Team. Prevalence of anti-gelatin IgE antibodies in people with anaphylaxis after measles-mumps rubella vaccine in the United States. Pediatrics 2002, 110, e71.
  33. Chu, D.K.; Abrams, E.M.; Golden, D.B.K.; Blumenthal, K.G.; Wolfson, A.R.; Stone, C.A., Jr.; Krantz, M.S.; Shaker, M.; Greenhawt, M. Risk of second allergic reaction to SARS-CoV-2 vaccines: A Systematic review and meta-analysis. JAMA Intern. Med. 2022, 182, 376–385.
  34. Greenhawt, M.; Abrams, E.M.; Shaker, M.; Chu, D.K.; Khan, D.; Akin, C.; Alqurashi, W.; Arkwright, P.; Baldwin, J.L.; Ben-Shoshan, M.; et al. The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and recommended evaluation and management: A systematic review, meta-analysis, GRADE assessment, and international consensus approach. J. Allergy Clin. Immunol. Pract. 2021, 9, 3546–3567.
  35. Ontario Agency for Health Protection and Promotion (Public Health Ontario). Reports of Events Managed as Anaphylaxis following COVID-19 Vaccines in Ontario: December 13, 2020 to March 6, 2021. Toronto, ON: Queen’s Printer for Ontario. 2021. Available online: https://www.publichealthontario.ca/-/media/documents/ncov/epi/covid-19-anaphylaxis-epi-summary.pdf?la=en (accessed on 16 March 2022).
  36. COVID; CDC; Response Team. Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 Vaccine—United States, December 14–23, 2020. Morb. Mortal. Wkly. Rep. 2021, 70, 46–51.
  37. Kadali, R.A.K.; Janagama, R.; Peruru, S.; Gajula, V.; Madathala, R.R.; Chennaiahgari, N.; Malayala, S.V. Non-life-threatening adverse effects with COVID-19 mRNA-1273 vaccine: A randomized, cross-sectional study on healthcare workers with detailed self-reported symptoms. J. Med. Virol. 2021, 93, 4420–4429.
  38. Mathioudakis, A.G.; Ghrew, M.; Ustianowski, A.; Ahmad, S.; Borrow, R.; Papavasileiou, L.P.; Petrakis, D.; Bakerly, N.D. Self-reported real-world safety and reactogenicity of COVID-19 vaccines: A vaccine recipient survey. Life 2021, 11, 249.
  39. Bae, S.; Lee, Y.W.; Lim, S.Y.; Lee, J.H.; Lim, J.S.; Lee, S.; Park, S.; Kim, S.K.; Lim, Y.J.; Kim, E.O.; et al. Adverse reactions following the first dose of ChAdOx1 nCoV-19 vaccine and BNT162b2 vaccine for healthcare workers in South Korea. J. Korean Med. Sci. 2021, 36, e115.
  40. Bianchi, L.; Biondi, F.; Hansel, K.; Murgia, N.; Tramontana, M.; Stingeni, L. Skin tests in urticaria/angioedema and flushing to Pfizer-BioNTech SARS-CoV-2 vaccine: LIMITS of intradermal testing. Allergy 2021, 76, 2605–2607.
  41. Corbeddu, M.; Diociaiuti, A.; Vinci, M.R.; Santoro, A.; Camisa, V.; Zaffina, S.; El Hachem, M. Transient cutaneous manifestations after administration of Pfizer-BioNTech COVID-19 Vaccine: An Italian single-centre case series. J. Eur. Acad. Dermatol. Venereol. 2021, 35, e483–e485.
  42. Riad, A.; Pokorna, A.; Attia, S.; Klugarova, J.; Koscik, M.; Klugar, M. Prevalence of COVID-19 vaccine side effects among healthcare workers in the Czech Republic. J. Clin. Med. 2021, 10, 1428.
  43. Dunkle, L.M.; Kotloff, K.L.; Gay, C.L.; Anez, G.; Adelglass, J.M.; Barrat Hernandez, A.Q.; Harper, W.L.; Duncanson, D.M.; McArthur, M.A.; Florescu, D.F.; et al. Efficacy and safety of NVX-CoV2373 in adults in the United States and Mexico. N. Engl. J. Med. 2022, 386, 531–543.
  44. Stuart, A.S.V.; Shaw, R.H.; Liu, X.; Greenland, M.; Aley, P.K.; Andrews, N.J.; Cameron, J.C.; Charlton, S.; Clutterbuck, E.A.; Collins, A.M.; et al. Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): A single-blind, randomised, phase 2, non-inferiority trial. Lancet 2022, 399, 36–49.
  45. Han, B.; Song, Y.; Li, C.; Yang, W.; Ma, Q.; Jiang, Z.; Li, M.; Lian, X.; Jiao, W.; Wang, L.; et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: A double-blind, randomised, controlled, phase 1/2 clinical trial. Lancet Infect. Dis. 2021, 21, 1645–1653.
  46. Blumenthal, K.G.; Robinson, L.B.; Camargo, C.A., Jr.; Shenoy, E.S.; Banerji, A.; Landman, A.B.; Wickner, P. Acute allergic reactions to mRNA COVID-19 vaccines. JAMA 2021, 325, 1562–1565.
  47. Amanzio, M.; Mitsikostas, D.D.; Giovannelli, F.; Bartoli, M.; Cipriani, G.E.; Brown, W.A. Adverse events of active and placebo groups in SARS-CoV-2 vaccine randomized trials: A systematic review. Lancet Reg. Health Eur. 2022, 12, 100253.
  48. Caubet, J.C.; Ponvert, C. Vaccine allergy. Immunol. Allergy Clin. North. Am. 2014, 34, 597–613.
  49. McNeil, M.M.; DeStefano, F. Vaccine-associated hypersensitivity. J. Allergy. Clin. Immunol. 2018, 141, 463–472.
  50. Kelso, J.M.; Greenhawt, M.J.; Li, J.T.; Nicklas, R.A.; Bernstein, D.I.; Blessing-Moore, J.; Cox, L.; Khan, D.; Lang, D.M.; Oppenheimer, J.; et al. Adverse reactions to vaccines practice parameter 2012 update. J. Allergy Clin. Immunol. 2012, 130, 25–43.
  51. Leventhal, J.S.; Berger, E.M.; Brauer, J.A.; Cohen, D.E. Hypersensitivity reactions to vaccine constituents: A case series and review of the literature. Dermatitis 2012, 23, 102–109.
  52. Kounis, N.G.; Koniari, I.; de Gregorio, C.; Velissaris, D.; Petalas, K.; Brinia, A.; Assimakopoulos, S.F.; Gogos, C.; Kouni, S.N.; Kounis, G.N.; et al. Allergic reactions to current available COVID-19 vaccinations: Pathophysiology, causality, and therapeutic considerations. Vaccines 2021, 9, 221.
  53. Nakayama, T.; Kumagai, T. Gelatin allergy. Pediatrics 2004, 113, 170–171.
  54. Shah, R.R.; Hassett, K.J.; Brito, L.A. Overview of vaccine adjuvants: Introduction, history, and current status. Methods Mol. Biol. 2017, 1494, 1–13.
  55. Kutlu, A.; Ucar, R.; Aydin, E.; Arslan, S.; Caliskaner, A.Z. Could aluminum be a new hidden allergen in type 1 hypersensitivity reactions when used as a drug additive? Postepy Dermatol. Alergol. 2016, 33, 243–245.
  56. Rouleau, I.; De Serres, G.; Drolet, J.P.; Skowronski, D.M.; Ouakki, M.; Toth, E.; Landry, M.; Menard, S.; Gagnon, R. Increased risk of anaphylaxis following administration of 2009 AS03-adjuvanted monovalent pandemic A/H1N1 (H1N1pdm09) vaccine. Vaccine 2013, 31, 5989–5996.
  57. Rouleau, I.; De Serres, G.; Skowronski, D.M.; Drolet, J.P.; Lemire, C.; Toth, E.; Landry, M. Risk factors associated with anaphylaxis and other allergic-like events following receipt of 2009 monovalent AS03-adjuvanted pandemic influenza vaccine in Quebec, Canada. Vaccine 2014, 32, 3480–3487.
  58. Justiz Vaillant, A.A.; Vashisht, R.; Zito, P.M. Immediate hypersensitivity reactions. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2022.
  59. Galli, S.J.; Tsai, M.; Piliponsky, A.M. The development of allergic inflammation. Nature 2008, 454, 445–454.
  60. Kneilling, M.; Rocken, M. Mast cells: Novel clinical perspectives from recent insights. Exp. Dermatol. 2009, 18, 488–496.
  61. Elieh Ali Komi, D.; Shafaghat, F.; Kovanen, P.T.; Meri, S. Mast cells and complement system: Ancient interactions between components of innate immunity. Allergy 2020, 75, 2818–2828.
  62. Nguyen, S.M.T.; Rupprecht, C.P.; Haque, A.; Pattanaik, D.; Yusin, J.; Krishnaswamy, G. Mechanisms governing anaphylaxis: Inflammatory cells, mediators, endothelial gap junctions and beyond. Int. J. Mol. Sci. 2021, 22, 7785.
  63. Kumar, M.; Duraisamy, K.; Chow, B.K. Unlocking the non-IgE-mediated pseudo-allergic reaction puzzle with mas-related g-protein coupled receptor member X2 (MRGPRX2). Cells 2021, 10, 1033.
  64. Porebski, G.; Kwiecien, K.; Pawica, M.; Kwitniewski, M. Mas-related G protein-coupled receptor-X2 (MRGPRX2) in drug hypersensitivity reactions. Front. Immunol. 2018, 9, 3027.
  65. Caballero, M.L.; Krantz, M.S.; Quirce, S.; Phillips, E.J.; Stone, C.A., Jr. Hidden dangers: Recognizing excipients as potential causes of drug and vaccine hypersensitivity reactions. J. Allergy Clin. Immunol. Pract. 2021, 9, 2968–2982.
  66. Kelso, J.M. Potential food allergens in medications. J. Allergy. Clin. Immunol. 2014, 133, 1509–1518.
  67. Ponvert, C.; Ardelean-Jaby, D.; Colin-Gorski, A.M.; Soufflet, B.; Hamberger, C.; de Blic, J.; Scheinmann, P. Anaphylaxis to the 23-valent pneumococcal vaccine in child: A case-control study based on immediate responses in skin tests and specific IgE determination. Vaccine 2001, 19, 4588–4591.
  68. Ponvert, C.; Scheinmann, P.; de Blic, J. Anaphylaxis to the 23-valent pneumococcal vaccine: A second explored case by means of immediate-reading skin tests with pneumococcal vaccines. Vaccine 2010, 28, 8256–8257.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
ScholarVision Creations
Feedback