Laurence Bouillet

Long COVID-19 syndrome appears after Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection with acute damage to microcapillaries, microthrombi, and endothelialitis. However, the mechanisms involved in these processes remain to be elucidated. All blood vessels are lined with a monolayer of endothelial cells called vascular endothelium, which provides a the major function is to prevent coagulation. A component of endothelial cell junctions is VE-cadherin, which is responsible for maintaining the integrity of the vessels through homophilic interactions of its Ca++-dependent adhesive extracellular domain. Here we provide the first evidence that VE-cadherin is a target in vitro for ACE2 cleavage because its extracellular domain (hrVE-ED) contains two amino acid sequences for ACE2 substrate recognition at the positions 256P-F257 and 321PMKP-325L. Indeed, incubation of hrVE-ED with the active ectopeptidase hrACE2 for 16 hrs in the presence of 10 μM ZnCl2 showed a dose-dependent (from 0.2 ng/μL to 2 ng/μL) decrease of the VE-cadherin immunoreactive band. In vivo, in the blood from patients having severe COVID-19 we detected a circulating form of ACE2 with an apparent molecular mass of 70 kDa, which was barely detectable in patients with mild COVID-19. Of importance, in the patients with severe COVID-19 disease, the presence of three soluble fragments of VE-cadherin (70, 62, 54 kDa) were detected using the antiEC1 antibody while only the 54 kDa fragment was present in patients with mild disease. Altogether, these data clearly support a role for ACE2 to cleave VE-cadherin, which leads to potential biomarkers of SARS-CoV-2 infection related with the vascular disease in “Long COVID-19”.

Angioedema (AE) is a reason for emergency care when it is severe. Care is difficult when the diagnostic is not known before the attack: mast cell (MC) or bradykinin (BK) mediated. One is very common but often benign, the other rare but potentially fatal. The French national reference center of angioedema (CREAK) provides emergency physicians with a hotline and a guideline to help them manage their patients. This study aimed to describe the clinical features of AE episodes prompting a call on the CREAK hotline and classify patients depending on the suspected cause of the AE. This is a retrospective study between March and August 2019. Each physician calling on the CREAK hotline was asked to fill a clinical description form for the AE emergency. Known patients of CREAK was excluded. Eighty four patients were included. Forty one (48.8%) in the angiotensin converting enzyme inhibitors induced acquired angioedema (ACEi-AAE), 39 (46.4%) in the mast cell induced angioedema, and 4 (4.8%) in the Bradykinin mediated angioedema. The mast cell induced angioedema patients have more history of hives (29.3%) than ACEi-AAE (2.4%, P = .0004). ACEi-AAE mainly affected the tongue (58.5% vs 25.6%, P = .003) and larynx (29.3% vs 13%, P = .001). In 65.5% of cases, the etiological diagnosis was not mentioned by the appellant, but made by the hotline. In 31% of cases, the hotline suggested the administration of a specific treatment not previously provided by the caller. All the doctors who called the hotline appreciate this tele-expertise especially in case of ACEi-AAE presumptions. In addition to providing rapid AE expertise, this service also allows to educate physicians in the management of AE irrespective of its origin.