Academic Journal
Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses
| Title: | Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses |
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| Authors: | 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., de la Rosa, K. |
| Publisher Information: | Cell Press |
| Publication Year: | 2024 |
| Collection: | Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository |
| Subject Terms: | Cardiovascular and Metabolic Diseases, Cancer Research, Technology Platforms, Topic 3: Integrative Biomedicine |
| Description: | 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. |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf; other |
| Language: | English |
| Relation: | https://edoc.mdc-berlin.de/id/eprint/24167/1/24167oa.pdf; https://edoc.mdc-berlin.de/id/eprint/24167/7/24167suppl.zip; Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses. 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. iScience 27 (3): 109330. 15 March 2024; PMID:38496296; https://doi.org/10.1016/j.isci.2024.109330 |
| DOI: | 10.1016/j.isci.2024.109330 |
| Availability: | https://edoc.mdc-berlin.de/id/eprint/24167/ https://edoc.mdc-berlin.de/24167/ https://doi.org/10.1016/j.isci.2024.109330 |
| Rights: | cc_by_nc_nd_4 |
| Accession Number: | edsbas.587F2C43 |
| Database: | BASE |
| DOI: | 10.1016/j.isci.2024.109330 |
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