COVID-19 disease in patients with hereditary and acquired angioedema with C1 inhibitor deficiency -a retrospective Czech Republic study

ABSTRACT

Background: Hereditary (HAE-C1- INH) and acquired (AAE C1-INH) angioedema with C1 inhibitor (C1 INH) deficiency are rare but potentially life-threatening conditions associated with bradykinin overproduction and recurrent episodes of angioedema without wheals. Increased susceptibility to infections or infection-associated fatal outcomes has not been previously described in this condition. However, in 2020 novel theories suggesting bradykinin as a potential mediator involved in lung injury in COVID-19 disease have been proposed. Therefore, a more severe course of COVID-19 infection in C1 INH deficient should be considered. Method(s) In September 2021, we performed a retrospective analysis of COVID-19 disease courses in HAE C1-INH and AAE C1-INH patients from Czech referral centers for the treatment of hereditary angioedema with C1 INH deficiency. Collected data involved basic demography, comorbidities, previous immunosuppressive treatment, COVID-19 symptoms and treatment, HAE symptoms during infection. Result(s) We identified 17 patients (10 females, 7 males) with C1 INH deficiency with COVID-19 positivity from March 2020 until September 2021 with median age of 45 years (10-80 years). Our cohort consisted of 16 HAE C1-INH patients (94%, HAE-1 15/ 16 -94%, HAE-2 1/16 -6%) and 1 AAE C1-INH patient (6%). Only 8 (47%) of the patients were receiving HAE prophylaxis. Most common comorbidity was obesity (4/17, 24%) followed by autoimmune disease (3/17, 18%), hypertension (3/17, 18%), immunodeficiency (3/ 17, 18%), prior immunosuppressive treatment (3/ 17, 18%) and malignancy (2/17, 12%). COVID-19 infection was asymptomatic in 3 of them (18%). Symptomatic patients reported most commonly fever (10/14, 67%), anosmia and ageusia (8/14, 53%) and headache (3/14, 20%). Only 2 symptomatic patients (14%) had pneumonia treated with antibiotics. None of our patients were treated with monoclonal antibodies or referred to the hospital. All the patients recovered. Two patients reported long-lasting symptoms more than 3 months after infection. Five patients (29%) experienced HAE attacks and in two of them, increased attack frequency lasted several weeks after recovery. Conclusion(s) According to our findings, we do not assume C1 INH deficiency to be a risk factor for a severe course of COVID-19 disease. However, as other infections, COVID-19 might trigger angioedema attacks and may cause increased attack frequency after recovery.