Abstract
Urticarial eruptions and angioedema are the most common cutaneous reactions in patients undergoing mRNA COVID-19 vaccinations. The vasoactive peptide bradykinin has long been known to be involved in angioedema and recently also in urticaria. Bradykinin is mainly catabolized by angiotensin-converting enzyme (ACE), which is inhibited by ACE inhibitors, a commonly employed class of antihypertensive drugs. We evaluated the risk of developing urticaria/angioedema after inoculation with the BNT162b2 mRNA COVID-19 vaccine in a population of 3586 health care workers. The influences of ACE inhibitors and selected potential confounding variables (sex, age, previous SARS-CoV-2 infection, and allergy history) were evaluated by fitting univariate and multivariable Poisson regression models. The overall cumulative incidence of urticaria/angioedema was 1.8% (65 out of 3586; 95% CI: 1.4–2.3%). Symptoms were mild, and no subject consulted a physician. Subjects taking ACE inhibitors had an adjusted three-fold increased risk of urticaria/angioedema (RR 2.98, 95% CI: 1.12–7.96). When we restricted the analysis to those aged 50 years or more, the adjusted RR was 3.98 (95% CI: 1.44–11.0). In conclusion, our data indicate that subjects taking ACE inhibitors have an increased risk of urticaria/angioedema after vaccination with the BNT162b2 mRNA COVID-19 vaccine. Symptoms are mild and self-limited; however, they should be considered to adequately advise subjects undergoing vaccination.
Highlights
After vaccination with the BNT162b2 mRNA COVID-19 vaccine, the main adverse events are short-term, mild-to-moderate pain at the injection site, fatigue, and headache [1]
The B-2 receptors are constitutively expressed in vascular endothelial and smooth muscle cells whereas the B-1 receptors, which are expressed in the microcirculation only at a very low level, are induced by interleukin 1 (IL-1) and tumor necrosis factor-α (TNF-α) during inflammation [17]
Data on previous SARS-CoV-2 infections were extracted from the laboratory databases, which contained results of real-time reverse transcriptase polymerase chain reaction (RTPCR) tests performed on nasopharyngeal swabs (NPSs)
Summary
After vaccination with the BNT162b2 mRNA COVID-19 vaccine, the main adverse events are short-term, mild-to-moderate pain at the injection site, fatigue, and headache [1]. Cutaneous reactions have been described in subjects undergoing mRNA COVID19 vaccinations and urticarial eruptions or angioedema were among the most common ones [2] It has been known for more than twenty years that the increase in vascular permeability that leads to angioedema, in several cases, is due to the potent vasoactive peptide bradykinin [3,4,5] and recent data indicate that increased bradykinin production is not limited to patients with angioedema and occurs in patients with urticaria [6]. The second pathway, which is present in plasma, leads to bradykinin generation through the cleavage of high-molecular-weight kininogen by plasma kallikrein during contact system activation [8,9]. We performed a cohort study of vaccinated health care workers of a large university hospital in Milan, Italy to calculate the cumulative incidence (risk) of urticaria/angioedema after completion of BNT162b2 COVID-19 vaccination and the impact of ACE inhibitors on this risk
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