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.
ABSTRACT
Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.