ABSTRACT
Background: The pandemic of Coronavirus disease 19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2), has become a global challenge in the last two years. SARS-CoV- 2 enters the cells of the infected subjects through angiotensin converting enzyme 2 (ACE-2), leading to its depletion on cell surface. ACE-2 activity is involved in the catabolism of des-Arg( 9)-bradykinin and increases the expression of angiotensin converting enzyme (ACE) in animal models. ACE in turn inactivates bradykinin. The infection has therefore the potential to cause a deregulation of the contact system and its pro-inflammatory activity, which could also contribute to the pathogenesis of COVID-19. Since bradykinin-mediated angioedema is generally thought to be the result of a poorly regulated contact system, it has been speculated that these patients are prone to severe SARS-CoV- 2 infection and that COVID-19 can in turn elicit angioedema attacks. We examined these hypotheses in a large group of bradykinin-mediated angioedema patients. Method(s): W e c onducted a m ulticenter r etrospective s tudy t argeting all the patients with hereditary angioedema (HAE) or acquired angioedema due to C1 inhibitor deficiency followed up by the centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA). All accessible patients underwent a telephone interview between January 1st and March 31st 2021;we collected data about demographic and angioedema features, the occurrence of SARS-CoV- 2 positivity and COVID-19 outcomes from the beginning of the pandemic until March 31st 2021. A digital diary of attacks developed by ITACA helped us to collect attacks data. 15 centers participated in the survey. Result(s): 677 patients were included;52/677 reported SARS-CoV- 2 positivity (48 with hereditary and 4 with acquired C1 inhibitor deficiency). The incidence was 7.68% (confidence interval 5,79-9,95%), similar to the general population (6.04%). 4/52 patients (7.7%) reported severe COVID-19;the median disease duration was 15 days. One patient suffered a pulmonary thromboembolism;no deaths were reported. 27/52 patients (51,9%) had angioedema attacks during the infection, with a median of 1 attack per patient;severity of COVID-19 predicted more frequent and more severe angioedema attacks in a multivariate analysis (p < 0.001). Conclusion(s): COVID-19 does not seem more severe in bradykinin-mediated angioedema than in the general population. SARS-CoV- 2 infection can elicit angioedema attacks.