Despite the progress in the understanding how COVID-19 infection may impact immunocompromised patients, the data on inborn errors of immunity (IEI) remain limited and ambiguous. Therefore, we examined the risk of severe infection course and hospital admission in a large cohort of patients with IEI. In this multicenter nationwide retrospective survey-based trial, the demographic, clinical, and laboratory data were collected by investigating physicians from 8 national referral centers for the diagnosis and treatment of IEI using a COVID-19-IEI clinical questionnaire. In total, 81 patients with IEI (including 16 with hereditary angioedema, HAE) and confirmed SARS-CoV-2 infection were enrolled, and were found to have a 2.3-times increased (95%CI: 1.44–3.53) risk ratio for hospital admission and a higher mortality ratio (2.4% vs. 1.7% in the general population). COVID-19 severity was associated with the presence of clinically relevant comorbidities, lymphopenia, and hypogammaglobulinemia, but not with age or BMI. No individuals with HAE developed severe disease, despite a hypothesized increased risk due to perturbed bradykinin metabolism. We also demonstrated a high seroconversion rate in antibody-deficient patients and the safety of anti-spike SARS CoV-2 monoclonal antibodies and convalescent plasma. Thus, IEI except for HAE, represent significant risk factors for a severe COVID-19. Therefore, apart from general risk factors, immune system dysregulation may also be involved in the poor outcomes of COVID-19. Despite the study limitations, our results support the findings from previously published trials.

<b><i>Introduction:</i></b> Acquired angioedema with C1 inhibitor deficiency (AAE-C1-INH) is rare but a potentially life-threatening disease. There are no official prevalence data, nor approved therapies for this condition. <b><i>Objective:</i></b> In this study, we aimed to collect and analyze clinical data on patients with AAE-C1-INH in the Czech Republic. <b><i>Methods:</i></b> We have conducted a retrospective analysis of AAE-C1-INH patients from Czech referral centers for the treatment of hereditary angioedema with C1 inhibitor deficiency. The inclusion criteria involved recurrent episodes of angioedema with the first manifestation at or after the age of 40, negative family history of angioedema, and C1 inhibitor function 50% or less. <b><i>Results:</i></b> A total of 14 patients (7 males and 7 females) met the inclusion criteria for AAE-C1-INH. The median age of the symptom onset was 59.5 years, and the median diagnosis delay was 1 year. The most common clinical manifestation was facial edema (100%) and upper airway swelling (85.7%). All patients responded to the acute attack treatment with icatibant and plasma-derived or recombinant C1 inhibitor concentrate. Lymphoid malignancy was identified in 9 patients (64%), monoclonal gammopathy of uncertain significance in 3 (21%), and in 1 patient autoimmune disease (ulcerative colitis) was considered causative (7%). We were not able to identify any underlying disease only in 1 patient (7%). In 6 of 7 patients (86%) treated for lymphoma, either a reduction in the frequency of angioedema attacks or both angioedema symptoms’ disappearance and complement parameter normalization was observed. <b><i>Conclusions:</i></b> The prevalence of AAE-C1-INH in the Czech Republic is about 1:760,000. This rare condition occurs in approximately 8% of the patients with angioedema with C1 inhibitor deficiency. AAE-C1-INH is strongly associated with lymphoproliferative disorders, and treating these conditions may improve the control of angioedema symptoms.

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Hereditární angioedém je vzácné onemocnění, jehož projevem jsou rekurentní angioedémy v různých lokalitách. Nejčastěji bývá podmíněn deficitem C1 inhibitoru. Za hlavní mediátor otoků považujeme u této diagnózy bradykinin. Lanadelumab je plně humánní monoklonální protilátka namířená proti plazmatickému kalikreinu, který z vysokomolekulárního kininogenu bradykinin vyštěpuje. Aktuálně je lanadelumab registrován pro dlouhodobou profylaktickou terapii hereditárního angioedému a představuje velmi účinnou a dobře tolerovanou léčebnou alternativu pro pacienty s častými a závažnými otoky.

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RATIONALE: Patients with hereditary angioedema due to C1 esterase inhibitor deficiency (C1-INH-HAE) are at risk for an attack during and after medical procedures; short-term prophylaxis may minimize this risk. This analysis evaluated recombinant C1-INH (rhC1-INH) as short-term prophylaxis prior to dental procedures. METHODS: Patients with angioedema received rhC1-INH prior to dental procedures; angioedema attacks were recorded through 2 days and >2-7 days postprocedure. RESULTS: 29 patients (median age, 44 years [range, 17.5-73.1 years]; 72.4% female; 89.7% HAE type I; median of 17 attacks/year [range, 0-90]) were treated for 37 procedures. More than half (56.8%) of the 37 dental procedures were extractions. A median rhC1-INH prophylactic dose of 3550 IU (range, 2100-4200 IU) was administered a median of 60 minutes prior to the dental procedure. Twenty-five (67.6%) cases had rhC1-INH administered 30-60 minutes preprocedure. Nine (24.3%) cases were also receiving long-term prophylaxis (danazol [n58]; tranexamic acid [n51]). Overall, 97.3% (36/37) of cases did not have an attack within 2 days postprocedure; 91.9% (34/37) during >2-7 days postprocedure. For the 1 attack occurring within 2 days, rhC1-INH (4200 IU; 37.5 IU/kg) was administered 230 minutes preprocedure; the patient experienced mild knee edema and required no treatment. No adverse events were reported. In a retrospective self-control subgroup, 15 (93.8%) of 16 dental procedures (no long-term/short-term prophylaxis preprocedure) were followed by an attack within 2 days after the procedure. CONCLUSIONS: Short-term prophylaxis with rhC1-INH, administered within ;60 minutes before a dental procedure, was efficacious and safe in patients with angioedema/C1-INH-HAE and reduced the risk of an attack postprocedure.

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