Allergic and cutaneous reactions following inactivated SARS‐CoV‐2 vaccine (CoronaVac^®) in healthcare workers

Dear Editor,

The vaccination programme against COVID‐19 was started in Turkey following agreement of the Turkish Ministry of Health on the supply of the inactivated SARS‐CoV‐2 vaccine (CoronaVac^®) by Sinovac Life Sciences (Beijing, China). We undertook a multicentre cross‐sectional study of all healthcare workers who had received this vaccine between 15 January and 15 March 2021.

A questionnaire was sent by email to 250 vaccinated healthcare workers in four hospitals in Turkey. The participants were asked to report any allergic and/or cutaneous reactions they noted within minutes to a few days after the first dose of inactivated SARS‐CoV‐2 vaccine (CoronaVac), and whether they had received any treatment for the reactions.

Of the 250 vaccinated healthcare workers, 221 [110 men (49.8%), mean age 37.03 ± 13.83; 111 women (50.2%), mean age 38.56 ± 13.29] responded to the questionnaire. Of these 221 responders, 62 (28.1%) reported allergic/cutaneous reactions (injection‐site pain and/or inflammatory reactions).

Of the 62 patients with cutaneous reactions, 25 (11.3%) of the cohort had no personal history of allergy or any personal or family history of COVID‐19, while the remaining 37 did.

The 25 patients without relevant personal/family history reported the following reactions (some patients had > 1 reaction): urticaria (n = 12, 5.4%) (Fig. 1a); papulosquamous reactions [i.e. pityriasis rosea (PR)‐like] (n = 8; 3.6%) (Fig. 1b); herpes infection (n = 4; 1.8%) consisting of herpes zoster (HZ) (n = 2) and herpes simplex (HS) (n = 2); angio‐oedema (n = 3; 1.4%), Type IV hypersensitivity reactions such as erythema multiforme, lichenoid drug eruption and drug hypersensitivity syndrome (n = 3; 1.4%); palmar erythema (n = 2; 0.9%) (Fig. 1c); anaphylaxis (n = 1; 0.5%); conjunctivitis (n = 1; 0.5%); and small vessel vasculitis (n = 1; 0.5%) (Fig. 1d).

Figure 1.

(a) Urticaria‐like lesions on the flanks; (b) pityriasis rosea‐like lesions on the trunk; (c) bilateral palmar erythema; (d) small vessel vasculitis on the extensor surface of the leg.

Of the 37 patients with relevant personal/family history, 36 had a personal history of allergy, of whom 13 (36.1%) developed cutaneous reactions following vaccination, particularly urticaria (n = 10), which was significantly (P < 0.001) more common than other reactions. Eight responders (7.2%; all women) reported exacerbation of their pre‐existing chronic atopic condition, which was controlled with short‐course systemic therapies.

Additionally, 21 responders had a personal history of COVID‐19‐related skin findings, of whom 12 (57.1%) developed skin rash after vaccination, mostly urticaria (n = 6) (P < 0.001), and 17 responders reported having relatives with COVID‐19‐related skin findings. Of these 17 responders, 10 developed skin rash after vaccination; 3 of these had urticaria (P < 0.001). Interestingly, constitutional symptoms occurring after vaccination were reported by 77 responders (34.8%) (Table 1).

Table 1.

Cutaneous and systemic reactions secondary to inactivated SARS‐CoV‐2 vaccine in healthcare workers who had received the first dose of the vaccine.

Vaccine‐induced reactions	Patients		P
	Male (N = 110), n (%)	Female (N = 111), n (%)
Skin findings	6 (5.5)	19 (17.1)	< 0.01
Flare‐up of chronic skin diseases	0 (0.0)	8 (7.2)	< 0.01
Injection‐site pain	20 (18.2)	42 (37.8)	0.001
Urticaria	2 (1.8)	10 (9.0)	0.02
Herpes reactivation	1 (0.9)	3 (2.7)	0.62
Angio‐oedema	0 (0.0)	3 (2.7)	0.25
Type IV allergic cutaneous rash	0 (0.0)	3 (2.7)	0.25
Papulosquamous/pityriasiform lesions	2 (1.8)	6 (5.4)	0.28
Anaphylaxis	0 (0.0)	1 (0.9)	1.00
Conjunctivitis	1 (0.9)	0 (0.0)	0.50
Vasculitic lesions	0 (0.0)	1 (0.9)	1.00
Palmar erythema	0 (0.0)	2 (1.8)	0.50
Systemic findings	32 (29.1)	45 (40.5)	0.07
Headache	25 (22.7)	28 (25.2)	0.66
Fever	0 (0.0)	6 (5.4)	0.03
Nausea. vomiting or diarrhoea	1 (0.9)	8 (8.1)	0.02
Fatigue/muscle pain/joint pain	8 (7.3)	34 (30.6)	< 0.001
Loss of taste or smell	1 (0.9)	2 (1.8)	1.00

Most of these reactions were improved without treatment within a few weeks of onset. Data on the safety, tolerability and immunogenicity of the inactivated SARS‐CoV‐2 vaccine (Coronavac) in healthy adults aged ≥ 60 years have been reported in the literature, ¹ stating that the Coronavac vaccine is safe and well‐tolerated in older adults. Adverse reactions were observed within 28 days of either the first or second dose of the vaccine with no significant cutaneous reactions. In our study, we noted that urticaria was the most frequently observed cutaneous reaction. Injection‐site pain, cutaneous reactions and constitutional symptoms related to the vaccine were observed mainly in female participants, which might be related to their immunological background. ² We also noted, in addition to development of PR, cases with reactivation of HS and HZ, supporting a causal link between the SARS‐CoV‐2 vaccine and herpesvirus reactivation. ³

Based on our observations, this inactivated SARS‐CoV‐2 vaccine was safe in terms of cutaneous and allergic reactions, except for one case of anaphylaxis. Although most of the reported reactions were transient in nature, reports of any reactions following SARS‐CoV‐2 vaccination may open a new horizon for case‐selected vaccines and precisely reach the clinical significance of these reactions. Further studies are warranted to answer the question of whether all or some of these reactions are markers of the degree of vaccine efficiency. Finally, physicians should be aware that SARS‐CoV‐2 vaccines have been approved for emergency use in the pandemic and long‐term efficacy and the related adverse effects are not yet fully clear.