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| Item Type: | Article |
|---|---|
| Title: | Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses |
| Creators Name: | Lebedin, M., Ratswohl, C., Garg, A., Schips, M., Vazquez Garcia, C., Spatt, L., Thibeault, C., Obermayer, B., Weiner, J., Moreno Velásquez, I., Gerhard, C., Stubbemann, P., Hanitsch, L.G., Pischon, T., Witzenrath, M., Sander, L.E., Kurth, F., 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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