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| Item Type: | Article |
|---|---|
| Title: | Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses |
| Creators: |
Lebedin, M.  ORCID: https://orcid.org/0000-0002-3877-7195, Ratswohl, C. ORCID: https://orcid.org/0000-0001-5413-0730, Garg, A., Schips, M., Vazquez Garcia, C. ORCID: https://orcid.org/0000-0003-4583-7616, Spatt, L., Thibeault, C., Obermayer, B. ORCID: https://orcid.org/0000-0002-9116-630X, Weiner, J. ORCID: https://orcid.org/0000-0003-1438-7819, Moreno Velásquez, I. ORCID: https://orcid.org/0000-0001-6058-8983, Gerhard, C. ORCID: https://orcid.org/0000-0001-6956-7249, Stubbemann, P., Hanitsch, L.G., Pischon, T. ORCID: https://orcid.org/0000-0003-1568-767X, Witzenrath, M., Sander, L.E., Kurth, F., Meyer-Hermann, M. and de la Rosa, K. ORCID: https://orcid.org/0000-0003-4809-3157
|
| 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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