COVID-19 vaccine not linked to risk of HAE worsening, study finds

Single-center study showed infection didn't always affect HAE

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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The use of vaccines against SARS-CoV-2, the virus that causes COVID-19, was not linked to an increased risk of disease worsening in people with hereditary angioedema (HAE), according to a small, single-center study from Turkey.

The study also found that the viral infection was not always associated with disease worsening or activation.

The study was published as a letter to the editor titled, “COVID-19 and vaccination in hereditary angioedema: Single center experience,” in the World Allergy Organization Journal.

“It is good to see that it is safe to administer [COVID-19] vaccines in our patients,” the authors wrote.

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The physicians retrospectively tracked 10 HAE patients following infection with and/or vaccination for COVID-19.

The two main types of HAE, types 1 and 2, are caused by mutations in a gene called SERPING1, which provides instructions for making a protein called C1-inhibitor (C1-INH). In HAE type 1, mutations lower the production of C1-INH. In type 2, the protein’s production is normal, but its activity is reduced. In the absence of functional C1-INH, there’s an overproduction of a signaling molecule called bradykinin that’s involved in inflammation and blood pressure regulation, which is believed to drive HAE swelling attacks.

The SARS-CoV-2 virus or vaccination against COVID-19 “may increase the frequency and severity of attacks” in HAE, the study’s authors said. That could happen because the virus reduces the levels and activity of an enzyme that normally breaks down bradykinin, causing its levels to rise following infection.

Patients evaluated for the study had a mean age of 31.8. Seven were women. Four had been diagnosed with HAE type 1, and six had HAE type 2.

Half of the patients had been infected with SARS-CoV-2. These patients had mild illness and had been treated with favipiravir, a broad-spectrum antiviral medication that has also been used to treat COVID-19.

Two HAE type 2 patients, a mother and daughter, experienced angioedema attacks during COVID-19 infection, which affected their abdomens. In the mother, attacks also affected the extremities and larynx, or voice box.

C1-INH concentrate, which provides the missing or faulty C1-INH protein to patients, was administered to both these patients. Despite treatment, HAE continued to worsen, as assessed by the Angioedema Activity Score 7 (AAS7), a scale measuring angioedema disease activity over the course of seven consecutive days. Scores increased from zero to 45 in the mother and to 60 in the daughter.

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HAE type and risk

Another family, a father and two daughters with HAE type 1, had COVID-19 without any disease attacks.

It’s not clear whether different HAE types are associated with a distinct risk for SARS-CoV-2 infection, the physicians noted.

Six of the 10 patients received COVID-19 vaccines. Some received CoronaVac, developed by Sinovac Biotech in China, and others had Turkovac, developed in Turkey. Both contain an inactivated version of the whole SARS-CoV-2 virus. The Pfizer/BioNTech mRNA vaccine, which delivers instructions to make a viral protein in the form of messenger RNA (mRNA) — the template that cells use to make proteins — also was used.

No increases in vaccine-related attacks were reported during vaccination, in the 72 hours thereafter, or a year later. And there was no worsening in disease severity after vaccination, with no patient showing an increase in AAS7 score.

Overall, the findings from the single-center study support the safety of inactivated and/or mRNA vaccines in HAE patients, and indicate that “SARS-CoV-2 infection does not always lead to [HAE] exacerbation or activation,” the researchers wrote.