COVID-19 Vaccination Safety and Tolerability in Patients Allegedly at High Risk for Immediate Hypersensitivity Reactions

Abstract

The reported incidence of immediate hypersensitivity reactions (IHR) including anaphylaxis after COVID-19 vaccination is 10-fold higher than for other vaccines. Several patient groups are theorized to be at particular risk. Since specific vaccination guidelines for these patients are based on expert opinion, we performed a retrospective monocentric analysis of the tolerability of adenoviral vector and mRNA-based COVID-19 vaccines in a cohort of patients allegedly at high risk of IHR. Reactions were assessed immediately on-site by allergists during a monitored vaccination protocol and after 3–7 days through telephone interviews. The cohort included 196 patients (aged 12–84 years) with primary mast cell disease (pMCD, 50.5%), idiopathic anaphylaxis (IA, 19.9%), hereditary angioedema (HAE, 5.1%) or miscellaneous indications (24.5%). Twenty-five immediate reactions were observed in 221 vaccine doses (11.3%). Most occurred in IA or miscellaneous patients. None fulfilled anaphylaxis criteria and most were mild and self-limiting. Reaction occurrence was significantly associated with female sex. In total, 13.5% of pMCD patients reported mast cell activation-like symptoms within 72 h post-vaccination. All pediatric pMCD patients (n = 9, 12–18 years) tolerated both mRNA-based vaccine doses. In summary, adenoviral vector and mRNA-based COVID-19 vaccines were safe and well-tolerated in patients with pMCD, HAE, and IA. No anaphylaxis was observed. The mild and subjective nature of most reactions suggests a nocebo effect associated with vaccination in a medicalized setting. Patients with pMCD could experience mild flare-ups of mast cell activation-like symptoms, supporting antihistamine premedication.

Allergic Reactions to COVID-19 Vaccination in High-Risk Allergic Patients: The Experience of Trieste University Hospital (North-Eastern Italy)

“…The higher proportion of allergic reactions to COVID-19 vaccines in females has already been reported 18 and is also consistent with the prevalence of allergic disease and particularly drug allergy in females [ 18 , 19 , 20 , 21 , 22 , 23 ]. Among the study group, food allergy was reported by 28.2% patients, drug allergy by 53.5% and 18.2% had a history of anaphylactic reaction to medications.…”

“…In our study, 8.7% of patients reporting allergic reactions (mainly urticaria and angioedema) within 4 h after immunization were treated with antihistamine and cortisone, whereas 21.6% developed reactions (mainly urticarial) >4 h after vaccination. Likewise, in a Belgian survey by telephone interviews, 25 (11.3%) immediate reactions were observed among 221 doses of m-RNA or adeno-viral vector vaccines administered to 196 patients at risk of immediate hypersensitivity reactions at the university hospital of Leuven (Belgium) [ 23 ]. By contrast, in the above Israeli study from Sheba Medical Centre in Tel Aviv, only 9 (2%) out of 429 highly allergic patients developed immediate reactions, three (0.7%) of which were anaphylactic [ 20 ].…”

“…The prevalence of skin reactions was 21.6% in the present study, a rather high figure not far from that (15%) reported for skin eruption and itching in the above Israeli study from Sheba Medical Centre [ 20 ]. Ieven et al [ 23 ] in 2022 also reported that 13.2% of late reactions had mast cell activation-like symptoms. However, the latter reactions were mild and self-limited in the present study.…”

Hereditary Angioedema with Normal C1 Esterase Inhibitor Refractory to Long-Term Prophylaxis: A Case Report

“…It is worth acknowledging that rarely, angioedema attacks have been noted post-vaccination in persons with a diagnosis of HAE as well as being implicated in an acquired case of angioedema [ 13 - 14 ]. However, other studies have asserted that mRNA vaccines are safe for administration in a variety of immediate-response hypersensitivity diseases, including HAE [ 13 , 15 ]. Hence, any link between angioedema in patients with HAE nC1-INH and COVID-19 vaccination is entirely speculative.…”

Immediate Hypersensitivity Reactions Induced by COVID-19 Vaccines: Current Trends, Potential Mechanisms and Prevention Strategies

“…In patients with hypersensitivity reactions or anaphylaxis following the first dose of an mRNA COVID-19 vaccine, it may be safe to administer fractionated doses (1/3 or 2/3) [ 70 ] or other formulations, such as protein-based vaccines. Patients at high risk for anaphylactic reactions have been suggested to refer to receive COVID-19 vaccination under medical supervision [ 109 , 118 ]. The recommendations help, through skin tests or in vitro tests, to identify the primary causative allergen of hypersensitivity reactions to these vaccines [ 70 ].…”