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Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses

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Title: Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses
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
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  – Url: https://edoc.mdc-berlin.de/id/eprint/24167/#
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  Data: Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses
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  Data: <searchLink fieldCode="AR" term="%22Lebedin%2C+M%2E%22">Lebedin, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Ratswohl%2C+C%2E%22">Ratswohl, C.</searchLink><br /><searchLink fieldCode="AR" term="%22Garg%2C+A%2E%22">Garg, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Schips%2C+M%2E%22">Schips, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Vazquez+Garcia%2C+C%2E%22">Vazquez Garcia, C.</searchLink><br /><searchLink fieldCode="AR" term="%22Spatt%2C+L%2E%22">Spatt, L.</searchLink><br /><searchLink fieldCode="AR" term="%22Thibeault%2C+C%2E%22">Thibeault, C.</searchLink><br /><searchLink fieldCode="AR" term="%22Obermayer%2C+B%2E%22">Obermayer, B.</searchLink><br /><searchLink fieldCode="AR" term="%22Weiner%2C+J%2E%22">Weiner, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Moreno+Velásquez%2C+I%2E%22">Moreno Velásquez, I.</searchLink><br /><searchLink fieldCode="AR" term="%22Gerhard%2C+C%2E%22">Gerhard, C.</searchLink><br /><searchLink fieldCode="AR" term="%22Stubbemann%2C+P%2E%22">Stubbemann, P.</searchLink><br /><searchLink fieldCode="AR" term="%22Hanitsch%2C+L%2EG%2E%22">Hanitsch, L.G.</searchLink><br /><searchLink fieldCode="AR" term="%22Pischon%2C+T%2E%22">Pischon, T.</searchLink><br /><searchLink fieldCode="AR" term="%22Witzenrath%2C+M%2E%22">Witzenrath, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Sander%2C+L%2EE%2E%22">Sander, L.E.</searchLink><br /><searchLink fieldCode="AR" term="%22Kurth%2C+F%2E%22">Kurth, F.</searchLink><br /><searchLink fieldCode="AR" term="%22Meyer-Hermann%2C+M%2E%22">Meyer-Hermann, M.</searchLink><br /><searchLink fieldCode="AR" term="%22de+la+Rosa%2C+K%2E%22">de la Rosa, K.</searchLink>
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  Label: Publisher Information
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  Data: Cell Press
– Name: DatePubCY
  Label: Publication Year
  Group: Date
  Data: 2024
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  Data: Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository
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  Data: <searchLink fieldCode="DE" term="%22Cardiovascular+and+Metabolic+Diseases%22">Cardiovascular and Metabolic Diseases</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+Research%22">Cancer Research</searchLink><br /><searchLink fieldCode="DE" term="%22Technology+Platforms%22">Technology Platforms</searchLink><br /><searchLink fieldCode="DE" term="%22Topic+3%3A+Integrative+Biomedicine%22">Topic 3: Integrative Biomedicine</searchLink>
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  Data: 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.
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  Data: 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
– Name: DOI
  Label: DOI
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  Data: 10.1016/j.isci.2024.109330
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  Data: https://edoc.mdc-berlin.de/id/eprint/24167/<br />https://edoc.mdc-berlin.de/24167/<br />https://doi.org/10.1016/j.isci.2024.109330
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