Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses
Authors
- M. Lebedin
- C. Ratswohl
- A. Garg
- M. Schips
- C. Vazquez Garcia
- L. Spatt
- C. Thibeault
- B. Obermayer
- J. Weiner
- I. Moreno Velásquez
- C. Gerhard
- P. Stubbemann
- L.G. Hanitsch
- T. Pischon
- M. Witzenrath
- L.E. Sander
- F. Kurth
- M. Meyer-Hermann
- K. de la Rosa
Journal
- iScience
Citation
- iScience 27 (3): 109330
Abstract
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.