COVID-19 and vaccination in hereditary angioedema: Single center experience

Like many microbial agents, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccination may increase the frequency and/or severity of attacks. We aimed to observe/evaluate patients with hereditary angioedema (HAE) followed by Sakarya University Research/Training Hospital pediatric allergy unit, Sakarya, Türkiye, for the effects of SARS-CoV-2 infection and COVID-19 vaccination. Ten HAE patients—3 males and 7 females—were evaluated retrospectively. Their mean age was 31.80 ± 19.15 (min. 12 – max. 66) years. Four of 10 patients were diagnosed with type 1 HAE and 6 with type 2 HAE. Two out of 6 patients (mother and daughter) diagnosed with type 2 HAE had angioedema attacks during COVID-19 disease. Six out of 10 HAE patients received different COVID-19 vaccines available in Türkiye up to third and fourth doses. There was no increase in COVID-19 vaccine-related attacks during, after 72 hours, and up to the year after vaccination. As a result, we consider it safe to administer inactivated and/or mRNA vaccines in our patients with HAE. In addition, catching SARS-CoV-2 infection was not always associated with disease exacerbation or activation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells via angiotensinconverting enzyme 2 (ACE2) and diminishes ACE2 expression, essential for bradykinin metabolism.Consequently, the accumulation of bradykinin occurs, which affects bradykinin receptors and causes vasodilation. 1,2Like many microbial agents, SARS-CoV-2 and its vaccination may increase the frequency and/or severity of hereditary angioedema (HAE) attacks. 3,4This study aimed to observe/evaluate HAE patients followed by Sakarya University Research/Training Hospital pediatric allergy unit, Sakarya, Türkiye, for the effects of SARS-CoV-2 infection and COVID-19 vaccination.
Ten patients with HAE-3 males and 7 femaleswere evaluated retrospectively (Table 1) with a mean age of 31.80AE 19.15 (min.12max.66) years (4 type 1 HAE and 6 type 2 HAE).Five out of 10 HAE patients have had a SARS-CoV-2 infection.The 4 patients who contracted SARS-CoV-2 had a mild illness.One (mother with type 2 HAE) had a mild-to-moderate disease due to her older age and co-morbidity such as hypertension.These patients had taken no other medication other than favipiravir, which was routinely used in the country for 5 days at the time.Two out of 5 patients (mother and her daughter) diagnosed with type 2 HAE had angioedema attacks during COVID-19 disease.While the mother had abdominal, extremity, and laryngeal attacks, her daughter had an abdominal attack.C1-INH concentrate was administered in repeated doses for the patients.Two patients with infection-related HAE attacks were evaluated with angioedema activity score (AAS) À7 scoring (Table 2).Despite the use of C1-INH replacement therapies during the attack, the score of the mother with type 2 HAE increased from 0 before the attack to 45 and that of her daughter to 60.However, another family (father and 2 daughters) diagnosed with type 1 HAE also had COVID-19 disease without any attack.Our 3 patients (Type 1 HAE) had no attacks, and 2/6 type 2 HAE patients had an attack during infection, which might be associated with the SARS-CoV-2 variant and a more significant C1-INH functional deficiency in these patients. 5We are unsure whether there is a difference between HAE types for getting SARS-CoV-2 infection since HAE types occur due to a different pathophysiology. 1 Six out of our 10 HAE patients received various COVID-19 vaccines [mRNA: BioNTechÒ and inactivated: SinovacÒ (CoronaVacÒ), and TurkovacÒ] available in Türkiye up to third and fourth doses.There was no increase in vaccine-related attacks during and after 72 hours and up to the year after vaccination. 5After vaccination, none of the patients showed an increase in AAS-7 scoring compared to before.COVID-19 vaccine-related angioedema attack development was previously described in patients with HAE.Although a slight increase in attacks has been reported, some study groups had no intense exacerbations. 1,6In a study, 5/31 patients (16.1%) experienced angioedema attacks 72 hours after the first dose. 7Another study demonstrated that one angioedema attack (1.2%) was found to be associated with the vaccination in Case #  a total of 86 doses.There was a slight increase in the typical amount of attacks in the year after vaccination. 4The authors found that 7.4% of vaccine doses intensified HAE attacks after the first vaccinations. 6Fijen et al, 8 and Ieven et al, 9 respectively, demonstrated 10% and 6.3% percentages of the first 2 vaccine doses followed by an HAE attack.

Gender
The possible interaction between COVID-19 vaccinations and long-term prophylaxis (LTP) agents, eg, attenuated androgens / Danazol, should be briefly mentioned in these patients.Danazol was used irregularly as LTP in a couple of our 10 HAE patients.Two of our 10 HAE patients used tranexamic acid as LTP as well.Furthermore, some of our HAE patients needed on-demand utilization of Icatibant and plasma-derived C1-INH concentrate.There have been concerns about the use of attenuated androgens, eg, Danazol, owing to its capacity to prevent the antiviral immune response to SARS-CoV-2 or modify the expression of the TMPRSS2 (Transmembrane Serine Protease 2) receptor, the SARS-CoV-2 utilizes. 2Some authors suggested putting HAE patients on short-term prophylaxis before vaccination. 4We did not observe any specific adverse effect linked with LTP (eg, Danazol or tranexamic acid) utilization during or after SARS-CoV-2 infection and vaccination, which is similar to some literature. 7 a result, it is good to see that it is safe to administer inactivated and/or mRNA vaccines in our patients.In addition, we have also observed that catching SARS-CoV-2 infection does not always lead to disease exacerbation or activation.

Table 1 .
Hereditary angioedema patients followed in our center during SARS-CoV-2 infection and vaccination.pd C1-INH: plasma derived C1-INH concentrate subjects were questioned on clinical manifestations and scheduled for a follow-up visit.

Table 2 .
Angioedema activity score (AAS)-7 of our hereditary angioedema patients followed in our center during SARS-CoV-2 infection and COVID-19 vaccination.AAS -7: angioedema activity score for daily scoring for 7 days