Results
From the 17th February to 17th May 2021 a total of 477234 [female
n=357481 (74.9%)] SA HCWs received a single, open-label dose of the
Ad26.COV2.S vaccine in the Sisonke phase 3B study. A total of 10,279
(2.2%) HCWs reported AEFI of which 139 (1.4%) AEFI. Searching of these
AEFI identified 569 possible allergic reactions for screening, and 318
could be excluded as non-allergic AEFI (Figure 1 ), leaving 251
(0.052%)probable allergic AEFI for an overall prevalence of 1 in 2000
doses. Thereafter, more detailed review including telephonic contact was
attempted for the 251 participants with probable allergic AEFI; of which
38/251 (15%) were uncontactable. Of the 251, 139 did not require / seek
medical attention.The majority [92/251 (36%)] reported a localized,
transient rash (morphology undocumented) or pruritis that was
self-limiting (lasting less than 24 hours), responsive to
over-the-counter medications, and not requiring contact with either a
family physician or emergency medical services. Six patients (2%) noted
isolated worsening of existing symptoms of allergic rhinoconjuncitivitis
in the 24 hours following vaccination, necessitating use of existing
allergic medications. Four participants (see exclusions Figure
1 ) reported delayed-onset of non-urticarial type rashes (one
blistering, two purpuric and one eczematous) all of which were referred
to specialist dermatologists. One of these cases had a confirmed
cutaneous vasculitis (on the basis of skin biopsy) and was known with
underlying systemic lupus erythematous.
Four cases of immediate allergic AEFI were adjudicated as anaphylaxis,
accounting for an overall prevalence of 8.4 per million doses.Table 1 details the four adjudicated cases of anaphylaxis that
met both Brighton Collaboration case definition (n=3/4 level 1, 1/4
level 3) of anaphylaxis and NIAID criteria. The median (IQR) age of
patients with anaphylaxis was 50 (45-53) years, and all cases were
female. The median (IQR) time to onset was 10 (9-52) minutes, with 3/4
cases having an onset of reaction within the 15 minute protocol
recommended observation time. All patients had a background of atopic
disease with all four giving a history of prior anaphylaxis to
medication. One patient had a history of vaccine-associated anaphylaxis
to a yellow fever vaccine. One of these patients had prior confirmed
SARS-CoV-2 infection. All patients required emergency room treatment,
with three being admitted to hospital. All patients except one received
epinephrine, antihistamines, intravenous (IVI) corticosteroids and
Beta-agonist therapies. All patients recovered completely.
Unfortunately, only 1/4 patients had a post-reaction tryptase
measurement; this single normal tryptase measurement was performed six
hours post-vaccine in a 56 year old female, known with uncontrolled
asthma, who presented with facial angioedema and bronchospasm 10 minutes
after vaccination (Table 1 ).
Mild/moderate allergic AEFI that necessitated treatment and contact with
the medical services occurred in 107/251 (43%). The commonest allergic
AEFI were delayed (>6 hours) reactions (n=69/107, 64%),
with isolated urticaria and/or angioedema (n=70/107, 65%) the most
frequently reported individual allergic phenotype (Table 2 ).
Table 2 shows demographic details, past medical and allergy
history, clinical features and management of non-anaphylactic allergy
AEFI needing medical attention, comparing immediate with delayed
reactions, and isolated urticaria and/or angioedema. Similar to
anaphylaxis cases, the majority [91/107 (85%)] of non-anaphylactic
allergy AEFI occurred in females with a median(IQR) age of 37 (27-43)
years. Reactogenicity was common, occurring in 67/107(63%)
participants. Overall 53/88 (60%) of participants with non-anaphylactic
allergy AEFI, had a history of prior anaphylaxis or atopic disease Of
the 24 immediate non-anaphylactic allergy AEFI, ten occurred within 15
minutes, seven between one and three hours, and five between 4-6 hours
post dosing [median(IQR) 0.75(1-3) hours)]. Amongst delayed
reactions, 24/69 (35%) started within 24 hours post dosing, with 29/69
(42%) starting between 3 and 21 days post vaccination.. Only eight
cases of non-anaphylactic allergy AEFI required admission to hospital
with the majority successfully treated with antihistamines 62/107 (58%)
and oral corticosteroids 30/107 (28%) only. Five patients in this group
received epinephrine treatment for either severe bronchospasm, or
angioedema of the upper respiratory tract due to concern around airway
swelling.
Isolated urticaria and/or angioedema was the commonest single allergic
reaction phenotype. The majority (39/70, 56%) occurred 24 hours or more
after dosing, with a median (IQR) of 48(11.5-120) hours. More than half
of these patients had no history of atopy. Only one patient in this
group needed hospitalisation, and only four needed to receive emergency
treatment.
Data on number of days of symptoms was not available; however all
patients, except four, reported complete resolution of their AEFI at the
time of telephonic contact (five to seven months post vaccination), with
the majority indicating that symptoms resolved within a week of onset.
Four patients reported urticaria and/or angioedema that was ongoing at
the time of contact and these patients have been referred for further
allergy care and management as chronic urticaria.