key: cord-0963419-da69friw
authors: Chiang, Valerie; Mok, Sabrina WS.; Chan, June KC.; Leung, Wai Yan; Ho, Carmen TK.; Au, Elaine YL.; Lau, Chak Sing; Lee, Tak Hong; Li, Philip H.
title: Experience of the first 1127 COVID-19 Vaccine Allergy Safety patients in Hong Kong – clinical outcomes, barriers to vaccination and urgency for reform
date: 2021-12-20
journal: World Allergy Organ J
DOI: 10.1016/j.waojou.2021.100622
sha: 73008636f603c20c886a29775e5c11b391a0c7fe
doc_id: 963419
cord_uid: da69friw

Introduction Hong Kong has had a low incidence of COVID-19 vaccine related anaphylaxis, partly due to its Vaccine Allergy Safety (VAS) guidelines for screening those at higher risk of COVID-19 vaccine-associated allergic reactions. We characterize the initial experience of the VAS clinics, as well as the impact of unnecessary referrals to the vaccination program. Methods All patients attending the VAS Clinics of the public and private health services between February and June, 2021 were reviewed. Results Out of 1127 patients assessed at VAS clinics, 1102 (97.8%) patients were recommended for vaccination. Out of those contacted, more than 80% (450/558) received vaccination successfully; the remaining had not yet booked their vaccinations. The majority (87.5%) of patients not recommended was due to potential excipient allergies. Males were significantly more likely to be recommended (OR= 5.822, 95% CI=1.361-24.903, p= 0.007), but no other features were associated with recommendation for vaccination. Almost half (45.1%) of public service referrals were rejected due to insufficient information or incorrect indications for referral. The majority of cases (56.2%) of patients referred for suspected “anaphylaxis” did not fulfil diagnostic criteria. Discussion COVID-19 vaccination is very safe and 98% of high-risk patients were recommended for vaccination. Barriers to VAS include a high proportion of inappropriate referrals, inaccurate diagnoses of anaphylaxis and inability to diagnose excipient allergies. Our data validates that a prior history of COVID-vaccine unrelated anaphylaxis should be removed as a precaution for vaccination. Closer collaborations between primary care and allergy specialists and changes in pharmaceutical legislation should be made a priority to promote vaccination uptake.

There was no source of funding for this study. COVID-19 vaccination is very safe and 98% of high-risk patients were recommended for 24 vaccination. Barriers to VAS include a high proportion of inappropriate referrals, inaccurate 25 diagnoses of anaphylaxis and inability to diagnose excipient allergies. Our data validates that 26 a prior history of COVID-vaccine unrelated anaphylaxis should be removed as a precaution for 27 vaccination. Closer collaborations between primary care and allergy specialists and changes 28 in pharmaceutical legislation should be made a priority to promote vaccination uptake. 29

Despite having one of the world's highest population density, Hong Kong has successfully kept 34 the spread of coronavirus disease 2019 (COVID-19) under control. In February 2021, Hong 35

Kong started its territory-wide COVID-19 vaccination program, providing its citizens with two 36 vaccine options: the Sinovac CoronaVac (SV) and Fosun Pharma BioNTech Comirnaty (BT). 37

The vaccination program is currently the most hopeful anti-COVID-19 strategy and is 39 anticipated to finally instigate the end of the pandemic. Although vaccine-associated allergic 40 reactions and anaphylaxis are extremely rare, even before the commencement of COVID-19 41 vaccinations in Hong Kong, the overall vaccine acceptance rate by the public was already 42 lower than 40% 1, 2 . This low acceptance rate was correlated with perceived harm of COVID-43 19 vaccination, as well as lack of trust in the healthcare system. Similar to other major cities, 44 reports of suspected anaphylaxis and severe allergic reactions after COVID-19 vaccination 45 rapidly dominated news reports, creating major safety concerns and vaccine hesitancy. vaccine-associated allergic reactions were defined by: (1) suspected allergic reaction(s) to 55 prior COVID-19 vaccination, (2) history of anaphylaxis or (3) a history of severe, immediate-56 type allergic reactions to multiple foods or more than one class of drugs. Individuals meeting 57 these criteria were recommended to defer COVID-19 vaccination until physician assessment, 58 and, if deemed necessary, they can be referred for formal allergist assessment to exclude 59 potential COVID-19 vaccine or excipient-associated allergies. Vaccination for COVID-19 60 vaccine-naïve patients was contraindicated in those whose potential excipient allergy could 61 not be excluded. However, these interim recommendations were primarily based on expert 62 consensus and not evidence based. Alike many countries, these recommendations are 63 subject to continuous update as further evidence regarding COVID-19 VAS emerges. 64

The HKIA and DH guidance proved to be successful in maintaining a low rate of COVID-19 66 vaccine-associated allergies. As of June 2021, there has only been 4 confirmed cases of 67 anaphylaxis (0.07 per 100,000 doses administered), a rate much lower than incidents 68 recorded by other countries 5-8 . This low anaphylaxis rate has been essential to maintain 69 vaccine confidence within the public and drive the target of achieving herd immunity. Clinic (hereafter referred to as the "XXX cohort") and private service run by the YYY for COVID-95

19 VAS (hereafter referred to as the "YYY cohort") between February to June, 2021 were 96 reviewed. The XXX and YYY are the only public and private hospitals, respectively, with 97

Specialists in Immunology & Allergy in Hong Kong; and likely represent the majority of 98 patients undergoing COVID-19 VAS evaluation during the study period. This would also 99 resolve any potential selection bias between public sector and private sector patients, as all 100 patient records were captured and analysed. As per HKIA recommendations, patients with a prior history of suspected "anaphylaxis" were 115 evaluated following the National Institute of Allergy and Infectious Disease and the Food type allergic reaction was classified to be Grade II or above by Ring and Messmer grading 11 . 118

Patients who never received any prior COVID-19 vaccination were categorized as "pre-119 vaccine", while those with suspected allergy to prior COVID-19 vaccination were categorized 120 as "post-vaccine". were those whose suspected potential excipient allergies could not be excluded. We 215 managed to contact half of the patients recommended for COVID-19 vaccination, of which 216 more than 80% confirmed that they had received subsequent vaccination safely, with no 217 reported immediate-type allergic reactions. The remaining have yet to book their 218 vaccinations, despite recommendation. 219 220 Association analysis revealed that males were significantly more likely to be recommended 221 for COVID-19 vaccination (i.e. female sex was associated with suspected COVID-19 vaccine or 222 excipient-associated allergies). A female predominance for suspected drug allergies has been 223 well reported, including in our previous beta-lactam allergy study in Hong Kong 16-18 . However, 224 our previous study suggested that sex may only be associated with allergy labelling, rather 225 than genuine allergy per se 16 vaccine allergy. Specialist-nurse led or telecommunication clinics to screen the 300 appropriateness of referrals or conducting pre-consultation assessments may also help in 301 reducing unnecessary vaccine deferrals. These inter-disciplinary initiatives would also provide 302 important patient counselling regarding VAS and encourage vaccination uptake, especially for 303 those who remain unwilling to receive vaccination despite lack of contraindications. Lastly, 304

we echo the HKIA consensus statement and implore that full excipient lists for all registered 305 drugs should be mandated in Hong Kong as soon as possible 3 . In the interim, a comprehensive 306 list of potentially cross-reactive formulations of drugs containing common excipients to 307 COVID-19 vaccines should also be made readily accessible for cross-referencing by healthcare 308 professionals. 309 310 Boosting COVID-19 vaccination coverage is a priority for all countries and populations. It is 311 imperative that allergy patients should not be excluded from vaccination for unproven 312 justifications and not to be diagnosed incorrectly with excipient allergies. It is equally 313 important that the public maintains confidence in vaccination safety. Appropriate VAS 314 guidance is important to maintain low anaphylaxis rates but this requires continuous updating 315 of guidelines as new evidence emerges, so that patients will be encouraged to undergo 316 vaccination and the community can achieve herd immunity. J o u r n a l P r e -p r o o f 

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