Background: Patients with
hereditary angioedema (HAE) have been postulated to be at increased risk for
coronavirus disease 2019 (COVID-19)
infection due to inherent dysregulation of the
plasma kallikrein-
kinin system. Only limited data have been available to explore this hypothesis. Objective: To assess the interrelationship(s) between
COVID-19 and HAE. Methods: Self-reported
COVID-19 infection, complications, morbidity, and mortality were surveyed by using an online questionnaire. The participants included subjects with HAE with C1 inhibitor (C1INH) deficiency (HAE-C1INH) and subjects with HAE with normal C1-inhibitor (HAE-nl-C1INH), and household controls (normal controls). The impact of HAE medications was examined. Results: A total of 1162 participants who completed the survey were analyzed, including: 695 subjects with HAE-C1INH, 175 subjects with HAE-nl-C1INH, and 292 normal controls. The incidence of reported
COVID-19 was not significantly different between the normal controls (9%) and the subjects with HAE-C1INH (11%) but was greater in the subjects with HAE-nl-C1INH (19%; p = 0.006).
Obesity was positively correlated with
COVID-19 across the overall population (p = 0.012), with a similar but nonsignificant trend in the subjects with HAE-C1INH. Comorbid
autoimmune disease was a risk factor for
COVID-19 in the subjects with HAE-C1INH (p = 0.047).
COVID-19 severity and complications were similar in all the groups. Reported
COVID-19 was reduced in the subjects with HAE-C1INH who received prophylactic subcutaneous C1INH (5.6%; p = 0.0371) or on-demand
icatibant (7.8%; p = 0.0016). The subjects with HAE-C1INH and not on any HAE medications had an increased risk of
COVID-19 compared with the normal controls (24.5%; p = 0.006). Conclusion: The subjects with HAE-C1INH who were not taking HAE medications had a significantly higher rate of reported
COVID-19 infection. Subcutaneous C1INH and
icatibant use were associated with a significantly reduced rate of reported
COVID-19. The results implicated potential roles for the
complement cascade and
tissue kallikrein-
kinin pathways in the pathogenesis of
COVID-19 in patients with HAE-C1INH.