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Article

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

1
Unit of Occupational Medicine, Department of Medical Surgical & Health Sciences, University of Trieste, 34129 Trieste, Italy
2
Unit of Occupational Medicine, University Health Agency Giuliano-Isontina (ASUGI), 34129 Trieste, Italy
3
Accident & Emergency, University Health Agency Giuliano-Isontina (ASUGI), 34129 Trieste, Italy
4
Directorate Office, Cattinara Hospital, University Health Agency Giuliano-Isontina (ASUGI), 34149 Trieste, Italy
5
Hospital Pharmacy, Giuliano Area, University Health Agency Giuliano-Isontina (ASUGI), 34128 Trieste, Italy
6
Public Health Department, University Health Agency Giuliano-Isontina (ASUGI), 34128 Trieste, Italy
*
Authors to whom correspondence should be addressed.
Vaccines 2022, 10(10), 1616; https://doi.org/10.3390/vaccines10101616
Submission received: 18 August 2022 / Revised: 12 September 2022 / Accepted: 23 September 2022 / Published: 27 September 2022

Abstract

:
Background. Allergic patients may develop reactions following COVID-19 vaccination more frequently than non-allergic individuals. The aim of our study was to assess the risk of reactions in high-risk allergic patients vaccinated for COVID-19 at the University Health Agency Giuliano-Isontina (ASUGI) of Trieste (northeastern Italy). Methods. Patients were considered at high risk for allergic reactions in case of: prior anaphylactic reaction to any drug/vaccine; multiple drug allergy; intolerance to polyethylene glycol (PEG) or polysorbate 80 (PS80) containing drugs; and mast cell disorders. High-risk allergic patients were immunized in hospital by a dedicated allergy team supported by resuscitation staff. Patients were interviewed over the phone one month after vaccination to complete a structured questionnaire investigating signs and symptoms developed after immunization. Results. From March 2021 to February 2022, 269 patients with a history of severe allergic reactions were assessed, of whom 208 (77.3%) eventually received COVID-19 vaccination, 50 (18.6%) refused to be immunized, 10 (3.7%) were deferred for medical reasons and one was declared exempted due to testing positive for PS80. Mild reactions (urticaria, angioedema, rhinitis, erythema) to COVID-19 vaccines were reported by 30.3% of patients, 8.7% within 4 h and 21.6% > 4 h after immunization. No anaphylactic events were observed. Although they were 80 times (3.8%) more prevalent than in COVID-19 vaccinees from the general population (0.047%), vaccine allergic reactions in high-risk patients were mainly mild and late, more likely affecting women (OR = 3.05; 95% CI 1.22–7.65). Conclusions. High-risk allergic patients with urticaria and angioedema may experience mild flare-ups of mast cell activation-like symptoms following COVID-19 vaccination, supporting antihistamine premedication before vaccination and to be continued for one week afterwards.

1. Introduction

In Italy, the vaccination campaign against COVID-19 started on 27 December 2020. COVID-19 vaccination was made mandatory for all health care workers (HCWs) from April 2021 and for individuals older than 50 from January 2022 onward. Unvaccinated HCWs were suspended from work or re-assigned to work tasks not entailing patient contact.
At the University Health Agency Giuliano-Isontina (ASUGI), the vaccination campaign against COVID-19 started with Comirnaty (Pfitzer-BioNTech, BNT162b2) and Vaxzevria (Astra Zeneca), and from May 2021 Spikevax (Moderna) was introduced. The risk of allergic reactions to COVID-19 vaccines was immediately a matter of concern due to the exclusion of allergic patients in phase-three clinical studies on Comirnaty [1] and patients with a history of allergic reaction to any component of COVID-19 vaccine or an allergy to other vaccines in Spikevax trials [2,3].
The risk of anaphylaxis after vaccination with Comirnaty was 11.1 per million injections in an initial report from the USA [4] and 4.7 cases per million doses in a greater population of vaccinees [5], an estimate 5–10 times higher than that reported for other non-COVID-19 vaccines [6].
Polyethylene glycol (PEG) and tromethamine for mRNA vaccines and polysorbate 80 (PS80) for Vaxzevria were immediately indicted as possible culprit allergens for allergic reactions [7] and specific recommendations were suggested to screen patients with a history of allergic reactions before immunizing them with COVID-19 vaccines [8,9,10].
In view of the above, the aim of this study was to assess allergic reactions following COVID-19 vaccination among high-risk allergic patients in ASUGI Trieste.

2. Materials and Methods

The present study was conducted according to the guidelines of the Declaration of Helsinki and approved by the ethical committee of the Friuli–Venezia Giulia region (CEUR- 2020-Os-072) on 16 April 2020. Patient consent was waived since, according to Italian privacy law (Legislative Decree 101/2018, D.Lgs 101/2018), patients’ data routinely collected by the Italian National Health Service (NHS) can be used for scientific purposes within the scope of approved studies/protocols, provided sensitive information is anonymized.
At the Unit of Occupational Medicine of Trieste Teaching Hospital, an allergy task force (ATF) was set up to assess the risk of allergic reactions to COVID-19 vaccines in high-risk allergic patients and their eligibility for vaccination within the catchment area of the health district of Trieste. General practitioners and health care staff at COVID-19 vaccination centers referred high-risk individuals with history of severe allergic reactions for immunization under special medical supervision.
In accordance with the open literature [7,9] and the guidelines of the Italian Association of Allergologists and Immunologists [11], patients with sensitivity to aeroallergens, latex, or contrast media, as well as patients with single-drug or venom allergy, were immunized under standard conditions and monitored for 60 min after vaccination. Patients meeting the following criteria underwent medical assessment by the ATF:
  • History of allergic or anaphylactic reaction to multiple oral or injectable drugs or vaccines;
  • History of idiopathic anaphylaxis;
  • History of mast cell disorders;
  • History of chronic urticaria;
  • History of uncontrolled asthma.
Multiple drug allergy was defined as a history of hypersensitivity to more than 1 drug group. An allergy workout was set up to evaluate drug intake in patients and their tolerance to excipients such as PEG and PS80.
Patients were considered at high risk of allergic reactions in case of:
  • Prior anaphylactic reaction to any drug or vaccine;
  • Multiple drug allergy without tolerance to PEG- or PS80-containing drugs;
  • Mast cell disorders;
  • Patients with uncontrolled asthma who had to be treated for their condition to achieve satisfactory control of their symptoms before being vaccinated for COVID-19.
Patients considered at high risk of allergic reaction were immunized in a hospital setting and monitored for 1–2 h following vaccination by a dedicated allergy team, including resuscitation medical staff. Although patients had to continue their usual anti-allergic therapy post immunization, including antihistamines [7], premedication was not recommended before any COVID-19 vaccine dose [11]. Upon administration of the second and third dose of the COVID-19 vaccine, health care staff asked vaccinees to report any reactions to previous doses. One month after immunization, patients were contacted by the ATF over the phone to complete a structured survey questionnaire investigating the signs and symptoms developed after any COVID-19 vaccine dose. Early adverse reactions were defined as those occurring within minutes to 4 h after vaccine administration; late reactions were defined as those developing >4 h after immunization [7,12]. Local reactions at the site of the injections were not considered in the analysis. Definitions of some immunological conditions and technical terms used across this manuscript can be viewed in Supplementary Table S1 [13,14,15,16,17].

3. Statistical Analysis

The data of patients developing reactions were compared with those not developing reactions.
Continuous data were reported as median (interquartile range, IQR) and mean ± standard deviation and compared using the Mann–Whitney test. Categorical data were compared by chi-square statistics.
Prevalence of allergic reactions in the study population was compared to that in the general population of the same area (Provinces of Trieste and Gorizia) obtained from regional surveillance system for reactions to COVID-19 vaccines.
A multivariable logistic regression was used to investigate risk factors for allergic reactions post COVID-19 vaccination, selecting terms significant at univariable analysis.
No variable had missing values. A p-value < 0.05 was set as a threshold for statistical significance.
Statistical analysis was performed using STATA 17 (STATA Corp, University City, TX, USA).

4. Results

Two hundred and sixty-nine patients with history of allergic reactions were assessed by the ATF of Trieste from March 2021 to February 2022. As can be seen from Figure 1, among the latter high-risk allergic group:
  • 208 (77.3%) patients received COVID-19 vaccination;
  • 50 (18.6%) patients refused to be immunized
  • 10 (3.7%) patients were deferred for medical reasons (uncontrolled asthma, ongoing urticarial reactions, other acute allergic diseases);
  • 1 patient tested positive for PEG and PS80 and was declared exempt from mandatory vaccination against COVID-19.
As can be seen from Table 1, high-risk allergic patients of ASUGI Trieste were predominantly females (79.6%) and had a median age of 55 years (IQR: 45–64 years). Moreover, 53.5% (=144/269) of patients had a history of drug allergy and 18.2% (=49/269) reported drug anaphylaxis. Food allergy was reported by 69 (25.6%) patients and 2.6% (=7/269) with food anaphylaxis. Eighteen patients underwent skin tests for PEG, none of whom were positive, whereas three were tested for PS80 with only one turning up positive.
One hundred and twenty patients were vaccinated under special medical supervision. Mild allergic reactions (urticaria, angioedema, rhinitis and erythema) post COVID-19 vaccinations occurred in 30.3% patients, 8.7% early (within 4 h) and 21.6% late (>4 h) after immunization. Figure 2a–c show the distribution of the allergic reactions by dose of COVD-19 vaccine received.
Table 2 displays the results of univariable as well as multivariable logistic regression analysis investigating risk factors for allergic reactions to COVID-19 vaccinations. As can be seen, females were more likely to develop an allergic reaction (OR = 3.05; 95% CI: 1.22; 7.65), whereas patients withhistory of allergic reactions to drugs had a significantly lower risk of reaction (OR = 0.30; 95% CI: 0.15; 0.58).
The details of the adverse reactions in each patient by COVID-19 vaccine dose in each patient can be viewed in Table 3. As can be seen, no allergic reaction within or after 4 h since COVID-19 vaccination involved two districts simultaneously (skin as well as respiratory system). Among the study group:
  • 29 patients developed an allergic reaction only to the first vaccine dose (orange coloured), of whom 8 were referred to ATF medical examination before dose 1 and 21 between dose 1 and dose 2.
  • 11 patients developed an allergic reaction only after the second vaccine dose (green coloured), of whom 3 were referred to ATF medical examination before dose 1 and 8 between dose 1 and dose 2.
  • 3 patients developed an allergic reaction only to the third dose (yellow coloured), all referred to ATF medical examination before dose 1.
  • 17 patients reacting to the first vaccine dose reacted also to the second (grey colored), of whom 5 were referred to ATF medical examination before the first dose and 12 between dose 1 and dose 2;
  • 2 patients referring to AFT medical examination before the first dose did not develop any allergic reaction to the first dose, but reacted after both dose 2 as well as dose 3 (pink colored);
  • 1 patient referring to ATF between first and second dose reacted against both dose 1 as well as dose 2;
  • No patient was referred to ATF medical examination after the second dose of COVID-9 vaccine.
Table 4 reports the aggregated adverse and allergic reactions to different COVID-19 vaccines in the general population of the Trieste–Gorizia catchment area, by dose administered. The overall prevalence of allergic reactions was 0.047% (=333/706,573 doses administered in 2021) and only 8 vaccinees were recorded in the Italian national surveillance system for adverse vaccine events. No cases of anaphylaxis occurred and reactions included urticarial, angioedema, itching, asthma and rhinitis events. Thirty-three cases were classified as “severe reactions” requiring treatment and medical support. Considering only official data, the prevalence of allergic reactions was significantly higher (p < 0.001) in vaccinated patients with history of severe allergy (3.8% = 8/208) compared to that in COVID-19 vaccinees from the general population (0.047%).

5. Discussion

Within the catchment area of ASUGI Trieste, 706,573 doses of COVID-19 vaccines were administered during calendar year 2021 to a total population 373,896 local residents. Vaccine hesitancy was immediately considered from the beginning of the campaign and an ATF was set up by ASUGI Trieste with the aim to evaluate patients with a history of multiple allergies and those with previous reactions to COVID-19 vaccines. In our cohort, 269 subjects were assessed because they were considered at higher risk of allergic reaction, 46 of whom already had an allergic reaction following a previous dose of COVID-19 vaccine.
Out of 208 patients vaccinated against COVID-19, none developed anaphylaxis or severe allergic reactions, whereas 63 (30.3%) reported an allergic reaction, mainly urticarial—with wide difference by sex (16.5% in females vs. 9.1% in males)—followed by angioedema, erythema/itching and a few cases of asthma/oculo-rhinitis. Vaccine reactions were overall mild and in a third of cases immediate, i.e., developing within four hours of vaccination. However, the prevalence of allergic reactions in immunized patients with history of severe allergy (3.8%) was 80 times that of COVID-19 vaccinees from the general population (0.047%) of the same catchment area.
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. Lower figures on food allergy (15.9%) and multiple drug allergy (32.9%) were found in a prospective cohort study conducted at Sheba Medical Centre (Tel Aviv, Israel) from 27 December 2020 to 22 February 2021 on 8102 patients with allergy history [20]. By contrast, the prevalence of food allergy in the general population is estimated to be <5% [14,21,24,25] and severe or multiple drug allergies is <1% [26].
In a study using US data from the Vaccine Adverse Event Reporting System (VAERS), out of 14,611 patients developing reactions, those with a history of allergy were more likely to develop immediate reactions after COVID-19 vaccination, especially vaccinees with history of anaphylaxis (OR 7.16; 95% CI 3.50–14.65) [13]. Likewise, in another analysis on VAERS data from 55 USA states between 14 December 2020 and 5 February 2021, out of 36,819,212 doses of COVID-19 vaccines administered as of 5 February 2021, the incidence of anaphylaxis among 12,630 COVID-19 vaccine recipients was 4.2 per million doses, with a risk of 1.85% (95% CI: 1.44%; 2.25%) among those with previous allergies and 7.91% (95% CI: 3.33%; 12.49%) among those with history of anaphylaxis [27]. In a further online survey on 1808 Polish respondents, 1707 of whom received two doses of Comirnaty, whilst reactions were far more likely after the second dose and among high-risk allergic patients, the majority of these reactions were mild and did not preclude the completion of the vaccination cycle [28].
In the present study, in case of a previous reaction to multiple drugs containing PEG or PS80 and intolerance to any drugs containing the latter two preservatives, skin tests were performed (N = 18 for PEG and N = 3 for PS80 and macrogol), finding only one positive reaction to PS80 in a patient with history of generalized reaction to PEG (5.6%). The utility of skin tests against the latter two preservatives is debatable although recommended by the Italian and International Societies for Allergic Diseases [7,11,29,30]. However, in a US study on 80 consecutive patients reporting allergic reactions to m-RNA COVID-19 vaccines, skin testing did not influence the tolerance against the second dose, which was well-received by the majority of vaccinees (N = 70) [31]. However, it is worth mentioning that COVID-19 vaccines contain several further excipients rarely inducing allergy, such as aluminum hydroxide, disodium EDTA, Matrix M™, Matrix-A and Matrix-C particles [32]. The latter excipients are not only included in vaccine preparations but can also be present in various everyday items, which could potentially sensitize users [33].
In our study, high-risk allergic patients were monitored for an extended time (at least 1 h) following vaccination and no cases of anaphylaxis were observed.
Allergic reactions to COVID-19 vaccines can be early, delayed or late [34,35]. Rapid reactions are mediated by IgE antibodies against a vaccine component, or via another mechanism activating mast cells [20] as a complement activation-related pseudoallergy (CARPA), already described for liposomes [29]. Other reactions include late onset of urticaria, eczema, erythema and itching [36,37]. Late-onset or delayed reactions following COVID-19 vaccination may include urticaria, eczema, erythema or itching hours to days after immunization, or late-onset local injection site reactions or swelling at the site of dermal fillers, developing several days after immunization [35,36,37].
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].
In the present study, only 8 (3.8%) patients had a relevant reaction according to the Italian Database for Adverse Event Following Immunization, whereas for other patients adverse reactions were mild and therefore were neglected.
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.

Strengths and Limitations

A strength of our study is the thorough and in-depth clinical assessment and follow up of each patient, thereby maximizing a reliable detection of allergic reactions to COVID-19 vaccination. Investigating vaccinees over the phone allowed us to identify symptoms in a detailed fashion, finding a very low incidence of severe reactions and a rather high incidence of mild and late allergic symptoms following immunization. Some published studies on the reactions to COVID-19 vaccines rely on health registries collecting adverse effects rather than actually following up vaccinees individually [2,20,38].
However, the present study also has some limitations. Patients reported allergic reactions after vaccination during a telephone interview, an approach potentially affected by recall bias and an overestimation of the reactions, since allergic people also tend to report very mild side effects after vaccination (nocebo effect). However, it is also well known that the Database for Adverse Event Following Immunization underestimates reactions because only significant or severe reactions tend to be reported.
Only in case of suspicion of allergy to PS80 or PEG skin tests were performed in the present study, hence a limited number of patients were tested, with only one subject resulting positive for PS80. As already mentioned, the utility of these skin tests and the relevance of sensitization to these two excipients is still under debate [31].
Furthermore, although skin tests against vaccines themselves were not performed, the assessment of allergy to COVID-19 vaccines by intradermal testing with the entire vaccine should be systematically considered, offering tailored immunization protocols (e.g., alternative vaccine, premedication, desensitization, etc.) to patients at high risk of allergic reactions [39].

6. Conclusions

The prevalence of mild yet late allergic reactions in immunized patients with a history of severe allergy was 80 times that in COVID-19 vaccinees’ from the general population. The use of antihistamine as premedication, to be continued for one week following immunization, may be considered to prevent these adverse reactions in selected patients appropriately screened.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/vaccines10101616/s1, Supplementary Table S1: Definition of the main immunological reactions, IgE mediated and not.

Author Contributions

Conceptualization: F.L.F.; study design: F.L.F.; investigation: F.L.F., I.L. and E.P.; data curation: E.P. and T.I.; data analysis: F.L.F. and L.C.; data interpretation: L.C. and F.L.F.; manuscript drafting (original draft): F.L.F. and L.C.; writing (reviewing/editing): E.P. and I.L.; resources: G.P. (Giuliano Ponis), G.P. (Giuseppe Perri), A.P. and G.R.; supervision: L.C. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the ethical committee of Friuli–Venezia Giulia (CEUR-2020-Os-072) on 16/04/2020.

Informed Consent Statement

Patient consent was waived since, according to Italian privacy law (Legislative Decree 101/2018, D.Lgs 101/2018), patients’ data routinely collected by the Italian National Health Service can be used for scientific purposes within the scope of approved studies/protocols, provided sensitive information is anonymized.

Data Availability Statement

The datasets generated and analyzed during the current study are not publicly available, since they were purposively collected by the authors for the present study, but they may be available from the corresponding author on reasonable request.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

PEG = polyethylene glycol; PS80 = polysorbate 800; ATF = allergy task force; VAERS = Vaccine Adverse Event Reporting System; CARPA = complement activation-related pseudoallergy; HCWs = health care workers.

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Figure 1. Patients with history of allergic reactions referred to the allergy task force (ATF) of Trieste from March 2021 to February 2022. PEG = polyethylene glycol; PS80 = polysorbate 80.
Figure 1. Patients with history of allergic reactions referred to the allergy task force (ATF) of Trieste from March 2021 to February 2022. PEG = polyethylene glycol; PS80 = polysorbate 80.
Vaccines 10 01616 g001
Figure 2. (ac) Distribution of allergic reactions by dose of COVID-19 vaccine administered. M = Males; F = Females.
Figure 2. (ac) Distribution of allergic reactions by dose of COVID-19 vaccine administered. M = Males; F = Females.
Vaccines 10 01616 g002
Table 1. Distribution of the study population. Number (N); column percentage (Col %); mean (M) ± standard deviation (SD); median and interquartile range (IQR). PS80 = Polysorbate 80.
Table 1. Distribution of the study population. Number (N); column percentage (Col %); mean (M) ± standard deviation (SD); median and interquartile range (IQR). PS80 = Polysorbate 80.
FACTORSMales
N (Col %)
Females
N (Col %)
Total
N (Col %)
p-Value *
Total patients55 (20.4)214 (79.6)269 (100)
Age (years)Mean ± SD53.7 ± 17.754.1 ± 14.454.0 ± 15.10.439
Median (IQR)53 (41–66)55 (45–64)55 (45–64)0.893
Atopic dermatitisNo53 (86.4)213 (93.9)40 (94.4)0.482
Yes2 (3.6)13 (6.1)15 (5.6)
Allergy to inhalantsNo37 (66.3)128 (59.8)165 (61.33)0.072
yesOthers17 (30.9)86 (40.2)103 (38.3)
Anaphylaxis1 (1.8)0 (0)1 (0.37)
Food allergyNo40 (72.7)153 (71.5)193 (71.8)0.159
YesOthers13 (23.6)56 (26.2)69 (25.6)
Anaphylaxis2 (3.6)5 (2.3)7 (2.6)
Drug allergyNo21 (38.2)55 (25.7)76 (28.3)0.159
YesOthers24 (43.6)120 (56.1)144 (53.5)
Anaphylaxis10 (18.2)39 (18.2)49 (18.2)
Hymenoptera allergyNo53 (96.4)200 (93.5)253 (94.0)0.001
YesOthers1 (1.8)11 (5.1)12 (4.5)
Anaphylaxis1 (1.8)3 (1.4)4 (1.5)
Latex allergyNo54 (98.2)178 (83.2)232 (86.2)0.001
YesOthers0 (0)36 (16.8)36 (13.4)
Anaphylaxis1 (1.8)0 (0)1 (0.4)
Contrast medium
allergy
No50 (90.9)199 (94.0)249 (92.5)0.459
YesOthers3 (5.4)5 (2.3)8 (3.0)
Anaphylaxis2 (3.6)10 (4.7)12 (4.5)
AsthmaNo48 (85.4)166 (77.6)?0.046
YesControlled8 (14.6)44 (20.6)52 (19.3)
Uncontrolled0 (0)4 (1.9)4 (1.5)
Chronic urticariaNo53 (96.4)96 (91.6)249 (92.6)0.229
Yes2 (3.6)18 (8.4)20 (7.4)
AngioedemaNo50 (89.9)201 (93.9)251 (93.3)0.425
Yes5 (9.1)13 (6.1)18 (6.7)
Idiopathic anaphylaxisNo53 (89.9)201 (98.6)264 (98.1)0.274
Yes2 (3.6)3 (1.4)5 (1.9)
Suspect Macrogol
allergy
No51 (92.7)206 (86.3)257 (95.5)0.257
Yes4 (7.3)8 (3.7)12 (4.5)
Suspect PS80 allergyNo54 (98.2)211 (98.6)265 (98.5)0.820
Yes1 (1.8)3 (1.4)4 (1.5)
Allergy testNo50 (89.9)198 (92.5)248 (92.2)0.195
YesMacrogol4 (7.3)14 (6.5)18 (6.7)
Macrogol + PS801 (1.8)2 (0.9)3 (1.1)
Positive reactions to Macrogol000NA
Positive reactions to PS80No02 (0.9)2 (0.75)NA
Yes1 (1.8)0 (0)1 (0.4)
COVID-19 vaccination under
medical supervision
No30 (54.6)119 (54.6)149 (55.4)0.805
Yes25 (45.4)95 (44.4)120 (44.6)
COVID-19
vaccination status
Vaccinated (1+ doses)44 (80.0)164 (76.6)208 (77.3)0.030
Refusing vaccination5 (9.1)44 (20.6)49 (18.2)
Vaccination deferred before dose 14 (7.3)6 (2.8)10 (3.7)
Exempted (allergy to PEG and PS80)1 (1.8)0 (0)1 (0.4)
Allergy consultancy
before COVID-19
vaccination
No4 (3.3)43 (19.3)47 (17.9)0.033
Yes51 (92.7)171 (80.7)222 (83.1)
Reactions to
COVID-19
vaccine
No32 (72.7)92 (56.1)124 (59.6)0.046
YesAny type of reaction12 (27.3)72 (43.9)84 (40.4)
At least one
allergic
reaction **
Total7 (15.9)56 (34.2)63 (30.3)0.019
<4 h since vaccination018 (11.0)18 (8.7)0.080
>4 h since vaccination7 (15.9)38 (23.1)45 (21.6)
* chi-square test (for categorical terms) or Wilkoxon test (for median differences) or ANOVA (for mean differences). ** Urticaria or angioedema or rhinitis or erythema (p compared vs no reactions)
Table 2. Univariable and multivariable logistic regression analysis on risk factors for allergic reactions following COVID-19 vaccinations. Odds ratios unadjusted (ORs) and adjusted (aORs) with 95% confidence intervals (95% CI).
Table 2. Univariable and multivariable logistic regression analysis on risk factors for allergic reactions following COVID-19 vaccinations. Odds ratios unadjusted (ORs) and adjusted (aORs) with 95% confidence intervals (95% CI).
FACTORSUNIVARIABLEMULTIVARIABLE
OR (95% CI)p-ValueaOR (95% CI)p-Value
Age (years, linear term)0.99 (0.97; 1.01)0.286
SexMalesreference reference
Females2.74 (1.14; 6.54)0.0233.05 (1.22; 7.65)0.017
Atopic dermatitisNoreference
Yes1.34 (0.38; 4.73)0.653
Inhalant allergyNoreference
Yes1.31 (0.72; 2.39)0.375
Food allergyNoreference
Yes0.91 (0.47;1.76)0.771
Drug allergyNoreference reference
Yes0.33 (0.18; 0.62)0.0010.30 (0.15; 0.58)<0.001
Venom allergyNoreference
Yes1.34 (0.38; 4.74)0.653
Latex allergyNoreference reference
Yes2.25 (1.00; 5.07)0.0501.81 (0.77; 4.24)0.172
Contrast medium
allergy
Noreference
Yes0.75 (0.23; 2.42)0.633
AsthmaNoreference
YesControlled1.15 (0.10; 12.9)0.910
Uncontrolled0.98 (0.46; 2.01)0.910
Chronic urticariaNoreference
Yes0.19 (0.02; 1.56)0.123
AngioedemaNoreference
Yes0.76 (0.20; 2.89)0.682
Number of allergic reactions (linear term)0.91 (0.68; 1.22)0.534
Vaccine typeComirnatyreference
Spikevax0.96 (0.39; 2.31)0.957
Vaxzevria1.83 (0.29; 11.4)0.855
Table 3. Allergic reactions to COVID-19 vaccination, reported by high-risk allergic patients of ASUGI Trieste. M = males; F = females.
Table 3. Allergic reactions to COVID-19 vaccination, reported by high-risk allergic patients of ASUGI Trieste. M = males; F = females.
Patient NumberSexAge(years)History of anaphylaxisSkin TestI doseII doseIII doseVaccine type by dose administered
Allergic symptomsTherapyAllergic symptomsTherapyAllergic symptomsTherapy
<4 h>4 h<4 h>4 h<4 h>4 hI DoseII DoseIII Dose
1F53 Urticaria Urticaria ComirnatySpikevax
2F34 Itching, erythema Erythema ComirnatyComirnaty
3F52 Urticaria Urticaria Cortisone and Antihistamine ComirnatyComirnaty
4F50 Angioedema UrticariaAntihistamine SpikevaxComirnaty
5F72 ItchingCortisone and Antihistamine ItchingCortisone and Antihistamine ComirnatyComirnaty
6F62 UrticariaAntihistamine UrticariaAntihistamine ComirnatyComirnaty
7F56 ErythemaAntihistamine Erythema SpikevaxSpikevaxSpikevax
8F65 Oculorinitis SpikevaxSpikevaxSpikevax
9F64 UrticariaCortisone and Antihistamine ComirnatyComirnatyComirnaty
10F49 Angioedema ComirnatyComirnatyComirnaty
11M70 Urticaria Urticaria ComirnatyComirnatyComirnaty
12F63 UrticariaCortisone and Antihistamine UrticariaCortisone and antihistamineSpikevaxSpikevaxSpikevax
13F78 UrticariaAntihistamine VaxzevriaVaxzevriaSpikevax
14F45 UrticariaAntihistamineUrticaria AntihistamineSpikevaxSpikevaxSpikevax
15F28Yes (drugs) Erythema Cortisone ed Antihistamine Comirnaty
16F30 Itching Cortisone ComirnatyComirnatySpikevax
17F56 Angioedema Cortisone Comirnaty
18F50 UrticariaAntihistamine ComirnatyComirnatySpikevax
19F25 Oculorinitis ComirnatyComirnatyComirnaty
20F70 Angioedema Cortisone ed Antihistamine VaxzevriaComirnatyComirnaty
21F74 Erythema VaxzevriaComirnatySpikevax
22F68 UrticariaCortisone ed Antihistamine UrticariaCortisoneComirnatyComirnatyComirnaty
23M62 Urticaria VaxzevriaComirnaty
24F42 Angioedema Cortisone and Antihistamine Spikevax
25F51Yes (drugs) Urticaria Antihistamine Comirnaty
26F45 Urticaria ComirnatyComirnaty
27F57 UrticariaAntihistamine ComirnatyComirnaty
28F44 Urticaria CortisoneUrticaria Cortisone VaxzevriaComirnaty
29F58 Urticaria AntihistamineUrticaria Cortisone and Antihistamine ComirnatyComirnaty
30F68Yes (drugs) Erythema JanssenComirnaty
31F25 PEG ItchingAntihistamine ComirnatyComirnaty
32F39 PEG UrticariaAntihistamine ComirnatyComirnatyComirnaty
33F71Yes (contrast medium) Urticaria ComirnatyComirnaty
34F56 Urticaria Comirnaty
35F58Yes (drugs) UrticariaCortisone Comirnaty
36F22 Asthma Comirnaty
37F32 Urticaria Comirnaty
38F66 Asthma ComirnatyComirnaty
39M53 Erythema SpikevaxSpikevax
40M52 ErythemaAntihistamine SpikevaxSpikevax
41F49Yes (drugs, food, contrast medium) Angioedema Angioedema ComirnatyComirnaty
42F78Yes (drugs) ItchingAntihistamine ComirnatyComirnaty
43M61 Urticaria ComirnatyComirnaty
44F59 Urticaria Urticaria ComirnatyComirnatyComirnaty
45F38 Erythema ComirnatyComirnatyComirnaty
46F69 UrticariaCortisone UrticariaCortisone ComirnatyComirnatyComirnaty
47F27 ErythemaAntihistamine ComirnatyComirnaty
48F73 Erythema Antihistamine VaxzevriaVaxzevria
49F55 AngioedemaCortisone AngioedemaCortisone ComirnatyComirnaty
50F60 UrticariaAntihistamine Urticaria, AsthmaCortisone and Antihistamine SpikevaxSpikevax
51M58 UrticariaAntihistamine ComirnatyComirnaty
52F60 Urticaria Spikevax
53F54 PEG and PS80 Erythema Spikevax
54F22 Urticaria Antihistamine ComirnatyComirnaty
55F37 AsthmaCortisone Comirnaty
56F51Yes (drugs) AsthmaCortisone ComirnatyComirnatyComirnaty
57F42 PEGUrticaria Cortisone and antihistamine Oculorinitis SpikevaxComirnaty
58F56 PEGErythema Cortisone ComirnatyNovavax
59F64 PEGAngioedema JanssenComirnaty
60F60Yes (drugs)PEG Asthma ComirnatyComirnaty
61M28Yes (drugs)PEG Urticaria Comirnaty
62F57 Urticaria ComirnatyComirnaty
63F49 Urticaria Urticaria ComirnatyComirnaty
Reactions only to dose I (Vaccines 10 01616 i001): N = 29. Reactions to doses I and II (Vaccines 10 01616 i002): N = 17. Reactions only to dose II (Vaccines 10 01616 i003): N = 11. Reactions to doses II and III (Vaccines 10 01616 i004): N = 2. Reactions only to dose III (Vaccines 10 01616 i005): N = 3. Reactions to doses I and III (Vaccines 10 01616 i006): N = 1.
Table 4. COVID-19 vaccines administered to the general population of ASUGI (Trieste–Gorizia catchment area) and adverse reactions reported by 31 December 2021. Number (N) and percentage of adverse reactions out of total vaccine doses.
Table 4. COVID-19 vaccines administered to the general population of ASUGI (Trieste–Gorizia catchment area) and adverse reactions reported by 31 December 2021. Number (N) and percentage of adverse reactions out of total vaccine doses.
I Dose
(N)
II Dose
(N)
III Dose
(N)
Total Doses
(N)
Total
Adverse
Reactions
N (%)
Allergic
Reactions *
N (%)
Vaxzevria (AstraZeneca)45,87342,735-88,608370 (0.41)64 (0.07)
Comirnaty (Pfizer BioNTech)215,426201,26698,510515,2021571 (0.30)223 (0.043)
Spikevax (Moderna)42,67033,21626,013101,899183 (0.18)44 (0.043)
Janssen (Johnson & Johnson)6936 15 (0.22)2 (0.029)
Unreported59325516864-
TOTAL311,498277,472124,539706,5732139 (0.30)333 (0.047)
* urticaria, angioedema, itching, asthma and rhinitis. Thirty-three cases were classified as “severe reactions” requiring treatment and medical support. No anaphylaxis was recorded.
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Filon, F.L.; Lazzarato, I.; Patriarca, E.; Iavernig, T.; Peratoner, A.; Perri, G.; Ponis, G.; Rocco, G.; Cegolon, L. Allergic Reactions to COVID-19 Vaccination in High-Risk Allergic Patients: The Experience of Trieste University Hospital (North-Eastern Italy). Vaccines 2022, 10, 1616. https://doi.org/10.3390/vaccines10101616

AMA Style

Filon FL, Lazzarato I, Patriarca E, Iavernig T, Peratoner A, Perri G, Ponis G, Rocco G, Cegolon L. Allergic Reactions to COVID-19 Vaccination in High-Risk Allergic Patients: The Experience of Trieste University Hospital (North-Eastern Italy). Vaccines. 2022; 10(10):1616. https://doi.org/10.3390/vaccines10101616

Chicago/Turabian Style

Filon, Francesca Larese, Ilaria Lazzarato, Emilia Patriarca, Thomas Iavernig, Alberto Peratoner, Giuseppe Perri, Giuliano Ponis, Giulio Rocco, and Luca Cegolon. 2022. "Allergic Reactions to COVID-19 Vaccination in High-Risk Allergic Patients: The Experience of Trieste University Hospital (North-Eastern Italy)" Vaccines 10, no. 10: 1616. https://doi.org/10.3390/vaccines10101616

APA Style

Filon, F. L., Lazzarato, I., Patriarca, E., Iavernig, T., Peratoner, A., Perri, G., Ponis, G., Rocco, G., & Cegolon, L. (2022). Allergic Reactions to COVID-19 Vaccination in High-Risk Allergic Patients: The Experience of Trieste University Hospital (North-Eastern Italy). Vaccines, 10(10), 1616. https://doi.org/10.3390/vaccines10101616

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