Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses

Autor: Mikhail Lebedin, Christoph Ratswohl, Amar Garg, Marta Schips, Clara Vázquez García, Lisa Spatt, Charlotte Thibeault, Benedikt Obermayer, January Weiner, 3rd, Ilais Moreno Velásquez, Cathrin Gerhard, Paula Stubbemann, Leif-Gunnar Hanitsch, Tobias Pischon, Martin Witzenrath, Leif Erik Sander, Florian Kurth, Michael Meyer-Hermann, Kathrin de la Rosa
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 3, Pp 109330- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.109330
Popis: Summary: Identifying immune modulators that impact neutralizing antibody responses against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is of great relevance. We postulated that high serum concentrations of soluble angiotensin-converting enzyme 2 (sACE2) might mask the spike and interfere with antibody maturation toward the SARS-CoV-2-receptor-binding motif (RBM). We tested 717 longitudinal samples from 295 COVID-19 patients and showed a 2- to 10-fold increase of enzymatically active sACE2 (a-sACE2), with up to 1 μg/mL total sACE2 in moderate and severe patients. Fifty percent of COVID-19 sera inhibited ACE2 activity, in contrast to 1.3% of healthy donors and 4% of non-COVID-19 pneumonia patients. A mild inverse correlation of a-sACE2 with RBM-directed serum antibodies was observed. In silico, we show that sACE2 concentrations measured in COVID-19 sera can disrupt germinal center formation and inhibit timely production of high-affinity antibodies. We suggest that sACE2 is a biomarker for COVID-19 and that soluble receptors may contribute to immune suppression informing vaccine design.
Databáze: Directory of Open Access Journals