Protease-anti-protease compartmentalization in SARS-CoV-2 ARDS: Therapeutic implications
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Mc Elvaney, O.F, et al. Protease-anti-protease Compartmentalization In Sars-cov-2 Ards: Therapeutic Implications. 2022. https://doi.org/10.17615/7ee9-9s90APA
Mc Elvaney, O., Asakura, T., Meinig, S., Torres Castillo, J., Hagan, R., Gabillard, C., Murphy, M., Thorne, L., Borczuk, A., Reeves, E., Zumwalt, R., Mikami, Y., Carroll, T., Okuda, K., Hogan, G., Mc Elvaney, O., Clarke, J., Mc Evoy, N., Mallon, P., Mc Carthy, C., Curley, G., Wolfgang, M., Boucher, R., & Mc Elvaney, N. (2022). Protease-anti-protease compartmentalization in SARS-CoV-2 ARDS: Therapeutic implications. https://doi.org/10.17615/7ee9-9s90Chicago
Mc Elvaney, O.F., T Asakura, S.L Meinig, J.L Torres Castillo, R.S Hagan, C Gabillard, M.P Murphy et al. 2022. Protease-Anti-Protease Compartmentalization In Sars-Cov-2 Ards: Therapeutic Implications. https://doi.org/10.17615/7ee9-9s90- Creator
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McElvaney, O.F.
- Other Affiliation: Beaumont Hospital
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Asakura, T.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Meinig, S.L.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Torres-Castillo, J.L.
- Affiliation: School of Medicine, Department of Medicine
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Hagan, R.S.
- Affiliation: School of Medicine, Department of Medicine
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Gabillard, C.
- Other Affiliation: Beaumont Hospital
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Murphy, M.P.
- Other Affiliation: Beaumont Hospital
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Thorne, L.B.
- Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine
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Borczuk, A.
- Other Affiliation: Weill Cornell Medicine
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Reeves, E.P.
- Other Affiliation: Beaumont Hospital
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Zumwalt, R.E.
- Other Affiliation: University of New Mexico School of Medicine
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Mikami, Y.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Carroll, T.P.
- Other Affiliation: Beaumont Hospital
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Okuda, K.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Hogan, G.
- Other Affiliation: Royal College of Surgeons in Ireland
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McElvaney, O.J.
- Other Affiliation: Beaumont Hospital
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Clarke, J.
- Other Affiliation: Beaumont Hospital
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McEvoy, N.L.
- Other Affiliation: Beaumont Hospital
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Mallon, P.W.
- Other Affiliation: University College Dublin
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McCarthy, C.
- Other Affiliation: University College Dublin
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Curley, G.
- Other Affiliation: Beaumont Hospital
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Wolfgang, M.C.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Boucher, R.C.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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McElvaney, N.G.
- Other Affiliation: Beaumont Hospital
- Abstract
- Background Interleukin-6 (IL-6) is elevated in SARS-CoV-2 infection. IL-6 regulates acute-phase proteins, such as alpha-1 antitrypsin (AAT), a key lung anti-protease. We investigated the protease-anti-protease balance in the circulation and pulmonary compartments in SARS-CoV-2 acute respiratory distress syndrome (ARDS) compared to non-SARS-CoV-2 ARDS (nsARDS) and the effects of tocilizumab (IL-6 receptor antagonist) on anti-protease defence in SARS-CoV-2 infection. Methods Levels and activity of AAT and neutrophil elastase (NE) were measured in plasma, airway tissue and tracheal secretions (TA) of people with SARS-CoV-2 ARDS or nsARDS. AAT and IL-6 levels were evaluated in people with moderate SARS-CoV-2 infection who received standard of care +/- tocilizumab. Findings AAT plasma levels doubled in SARS-CoV-2 ARDS. In lung parenchyma AAT levels were increased, as was the percentage of neutrophils involved in NET formation. A protease-anti-protease imbalance was detected in TA with active NE and no active AAT. The airway anti-protease, secretory leukoprotease inhibitor was decreased in SARS-CoV-2-infected lungs and cleaved in TA. In nsARDS, plasma AAT levels were elevated but TA samples had less AAT cleavage, with no detectable active NE in most samples. Induction of AAT in ARDS occurred mainly through IL-6. Tocilizumab down-regulated AAT during SARS-CoV-2 infection. Interpretation There is a protease-anti-protease imbalance in the airways of SARS-CoV-2-ARDS patients. This imbalance is a target for anti-protease therapy. Funding NIH Serological Sciences Network, National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases.
- Date of publication
- 2022
- Keyword
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- License
- Attribution 4.0 International
- Journal title
- eBioMedicine
- Journal volume
- 77
- Page start
- 103894
- Language
- English
- Version
- Publisher
- ISSN
- 2352-3964
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