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| Item Type: | Article |
|---|---|
| Title: | Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses |
| Creators Name: | Lebedin, M. and Ratswohl, C. and Garg, A. and Schips, M. and Vazquez Garcia, C. and Spatt, L. and Thibeault, C. and Obermayer, B. and Weiner, J. and Moreno Velásquez, I. and Gerhard, C. and Stubbemann, P. and Hanitsch, L.G. and Pischon, T. and Witzenrath, M. and Sander, L.E. and Kurth, F. and Meyer-Hermann, M. and de la Rosa, K. |
| 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. |
| Source: | iScience |
| ISSN: | 2589-0042 |
| Publisher: | Cell Press |
| Volume: | 27 |
| Number: | 3 |
| Page Range: | 109330 |
| Date: | 15 March 2024 |
| Official Publication: | https://doi.org/10.1016/j.isci.2024.109330 |
| PubMed: | View item in PubMed |
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