tetano
Editor, Senior Moderator
iScience
. 2024 Feb 24;27(3):109330.
doi: 10.1016/j.isci.2024.109330. eCollection 2024 Mar 15. Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses
Mikhail Lebedin[SUP] 1 2 [/SUP], Christoph Ratswohl[SUP] 1 3 [/SUP], Amar Garg[SUP] 4 [/SUP], Marta Schips[SUP] 4 [/SUP], Clara Vázquez García[SUP] 1 2 [/SUP], Lisa Spatt[SUP] 1 [/SUP], Charlotte Thibeault[SUP] 5 [/SUP], Benedikt Obermayer[SUP] 6 [/SUP], January Weiner[SUP] 6 [/SUP], Ilais Moreno Velásquez[SUP] 7 [/SUP], Cathrin Gerhard[SUP] 1 [/SUP], Paula Stubbemann[SUP] 5 [/SUP], Leif-Gunnar Hanitsch[SUP] 5 [/SUP], Tobias Pischon[SUP] 2 7 8 [/SUP], Martin Witzenrath[SUP] 5 9 10 [/SUP], Leif Erik Sander[SUP] 5 9 11 [/SUP], Florian Kurth[SUP] 5 9 [/SUP], Michael Meyer-Hermann[SUP] 4 12 [/SUP], Kathrin de la Rosa[SUP] 1 2 11 [/SUP]
Affiliations
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.
Keywords: Human specimen; Immune response; In silico biology; Properties of biomolecules.
. 2024 Feb 24;27(3):109330.
doi: 10.1016/j.isci.2024.109330. eCollection 2024 Mar 15. Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses
Mikhail Lebedin[SUP] 1 2 [/SUP], Christoph Ratswohl[SUP] 1 3 [/SUP], Amar Garg[SUP] 4 [/SUP], Marta Schips[SUP] 4 [/SUP], Clara Vázquez García[SUP] 1 2 [/SUP], Lisa Spatt[SUP] 1 [/SUP], Charlotte Thibeault[SUP] 5 [/SUP], Benedikt Obermayer[SUP] 6 [/SUP], January Weiner[SUP] 6 [/SUP], Ilais Moreno Velásquez[SUP] 7 [/SUP], Cathrin Gerhard[SUP] 1 [/SUP], Paula Stubbemann[SUP] 5 [/SUP], Leif-Gunnar Hanitsch[SUP] 5 [/SUP], Tobias Pischon[SUP] 2 7 8 [/SUP], Martin Witzenrath[SUP] 5 9 10 [/SUP], Leif Erik Sander[SUP] 5 9 11 [/SUP], Florian Kurth[SUP] 5 9 [/SUP], Michael Meyer-Hermann[SUP] 4 12 [/SUP], Kathrin de la Rosa[SUP] 1 2 11 [/SUP]
Affiliations
- PMID: 38496296
- PMCID: PMC10940809
- DOI: 10.1016/j.isci.2024.109330
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.
Keywords: Human specimen; Immune response; In silico biology; Properties of biomolecules.