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

• DOI: 10.1016/j.isci.2024.109330
• Publication Date: 2024-02-24T17:06:02Z
• Authors: Mikhail Lebedin; Christoph Ratswohl; Amar Garg; Marta Schips; Clara Vázquez García; Lisa Spatt; Charlotte Thibeault; Benedikt Obermayer; January Weiner; Ilais Moreno Velá...; Cathrin Gerhard; Paula Stubbemann; Leif-Gunnar Hanitsch; Tobias Pischon; Martin Witzenrath; Leif Erik Sander; Florian Kurth; Michael Meyer-Her...; Kathrin de la Rosa
• Keywords: 0301 basic medicine; Cancer Research; In silico biology; Science; Q; Article; 03 medical and health sciences; Cardiovascular and Metabolic Diseases; Integrative Biomedicine [Topic 3]; Properties of biomolecules; Technology Platforms; Immune response; Human specimen

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.