Patients with hereditary angioedema and patients with SARS-CoV-2-associated pneumonia – what can be similar?

INTRODUCTION: Hereditary angioedema (HAE) is a rare, autosomal dominant genetic disorder that leads to sporadic episodes of swelling, which can affect any part of the body. In most cases, HAE is caused by a deficiency (type I) or dysfunction (type II) of C1-inhibitor (C1-INH), with an estimated prevalence of 1:10.000–1:50.000. HAE type I characterized by low antigenic and functional C1-INH levels, HAE type II characterized by normal or elevated antigenic but low functional C1-INH levels. MATERIALS AND METHODS: Study groups included: patients with genetically confirmed HAE type I (group 1, n = 49); patients with genetically confirmed HAE type II (group 2, n = 13); patients with SARS-CoV-2-associated pneumonia with a median recovery period of 5 months (group 3, n = 11); patients with SARS-CoV-2 infection and without pneumonia with a median recovery period of 5 months (group 4, n = 41). The expression of the C1-INH gene was measured when HAE patients were not on prophylactic treatment. The results presented as a median (25%; 75%). C1-INH expression levels (normal range: 1.47 REU (1.07; 2.01)) were measured using real-time PCR and normalized to the level of GUS gene expression. All subjects consented to the study. RESULTS: The expression of the C1-INH gene in the first group was 0.31 REU (0.19; 0.60); in the second – 1.45 REU (1.26; 2.87); in the third – 0.47 REU (0.32; 0.88) and in the fourth – 0.76 REU (0.57; 1.29). We revealed that the third group had the similar range of C1-INH gene expression as in patients with HAE type I who have primary quantitative deficiency of C1-INH. Only in 27.3% (3/11) patients from group 3 and in 70.7% (29/41) patients from group 4 after recover from SARS-CoV-2 infection the expression level of the C1-INH gene have returned to the normal range. CONCLUSION: A recent studies displays that SARS-CoV-2 infection in human body directly causes a deficit in C1-INH, also there are evidences of the successful use of replacement therapy with a C1-INH in severe cases of COVID-19. However, the reason for the persistence of an acquired C1-INH deficiency in patients even with a several month recovery period remains to be elucidated.