SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care
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| Titel: | SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care |
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| Autoren: | Stefan R. Bornstein, Umar Niazi, Torsten Tonn, Ella Reed, Mark J. W. McPhail, Adam Nabeebaccus, Rafael Fernandez-Leiro, Francesca Trovato, Ajay M. Shah, Konstantina Dimitrakopoulou, Georg Auzinger, Adrian Hayday, Manu Shankar-Hari, Blair Merrick, Jonathan D. Edgeworth, Manuel Mayr, Xiaoke Yin, Konstantinos Theofilatos, Salvatore Napoli, Kaloyan Takov, Mauro Giacca, Sean A. Burnap, Salma F Mujib, Barnaby Sanderson, Katie J. Doores, Mansoor Saqi, Matthew Fish, Romy Kronstein-Wiedemann, Christian Cassel, Kevin O'Gallagher, Hashim Ali, Bhawana Singh, Clemens Gutmann, Silke Braun, Marieke Rienks, Maria Hasman, Lukas E Schmidt |
| Weitere Verfasser: | British Heart Foundation, NHS Foundation Trust, UK Research & Innovation (UKRI), Medical Research Council UK (MRC), Unión Europea. Comisión Europea. European Research Council (ERC), Unión Europea, Leducq Foundation, Wellcome Trust, Cancer Research UK, DSpace at Cambridge pro (8.1) |
| Quelle: | Nat Commun Repisalud Instituto de Salud Carlos III (ISCIII) Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021) Gutmann, C, Takov, K, Burnap, S A, Singh, B, Ali, H, Theofilatos, K, Reed, E, Hasman, M, Nabeebaccus, A, Fish, M, McPhail, M J, O'Gallagher, K, Schmidt, L E, Cassel, C, Rienks, M, Yin, X, Auzinger, G, Napoli, S, Mujib, S F, Trovato, F, Sanderson, B, Merrick, B, Niazi, U, Saqi, M, Dimitrakopoulou, K, Fernández-Leiro, R, Braun, S, Kronstein-Wiedemann, R, Doores, K J, Edgeworth, J D, Shah, A M, Bornstein, S R, Tonn, T, Hayday, A C, Giacca, M, Shankar-Hari, M & Mayr, M 2021, 'SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care', Nature Communications, vol. 12, no. 1, 3406. https://doi.org/10.1038/s41467-021-23494-1 Gutmann, C, Takov, K, Burnap, S A, Singh, B, Ali, H, Theofilatos, K, Reed, E, Hasman, M, Nabeebaccus, A, Fish, M, McPhail, M J, O'Gallagher, K, Schmidt, L E, Cassel, C, Rienks, M, Yin, X, Auzinger, G, Napoli, S, Mujib, S F, Trovato, F, Sanderson, B, Merrick, B, Niazi, U, Saqi, M, Dimitrakopoulou, K, Fernández-Leiro, R, Braun, S, Kronstein-Wiedemann, R, Doores, K J, Edgeworth, J D, Shah, A M, Bornstein, S R, Tonn, T, Hayday, A C, Giacca, M, Shankar-Hari, M & Mayr, M 2021, ' SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care ', Nature Communications, vol. 12, no. 1, 3406 . https://doi.org/10.1038/s41467-021-23494-1 Gutmann, C, Takov, K, Burnap, S A, Singh, B, Ali, H, Theofilatos, K, Reed, E, Hasman, M, Nabeebaccus, A, Fish, M, McPhail, M J, O'Gallagher, K, Schmidt, L E, Cassel, C, Rienks, M, Yin, X, Auzinger, G, Napoli, S, Mujib, S F, Trovato, F, Sanderson, B, Merrick, B, Niazi, U, Saqi, M, Dimitrakopoulou, K, Fernández-Leiro, R, Braun, S, Kronstein-Wiedemann, R, Doores, K J, Edgeworth, J D, Shah, A M, Bornstein, S R, Tonn, T, Hayday, A C, Giacca, M, Shankar-Hari, M & Mayr, M 2021, ' SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care ', Nature Communications, vol. 12, no. 1, pp. 3406 . https://doi.org/10.1038/s41467-021-23494-1 |
| Verlagsinformationen: | Springer Science and Business Media LLC, 2021. |
| Publikationsjahr: | 2021 |
| Schlagwörter: | Male, Proteomics, 0301 basic medicine, HEPARAN-SULFATE PROTEOGLYCANS, Kaplan-Meier Estimate, Viral/blood, DISEASE, ACTIVATION, Tumor/metabolism, 2. Zero hunger, Serum Amyloid P-Component/metabolism, 0303 health sciences, COVID-19/metabolism, Antigens, Neoplasm/metabolism, GLYCOPROTEIN, Middle Aged, Viral Load, Antibodies, Neutralizing/immunology, Spike Glycoprotein, 3. Good health, Serum Amyloid P-Component, Neoplasm/metabolism, C-Reactive Protein, Spike Glycoprotein, Coronavirus, RNA, Viral, Female, Proteomics/methods, Adult, Critical Care, Science, INHIBITION, Antibodies, Article, 03 medical and health sciences, SARS-CoV-2/genetics, Antigens, Neoplasm, MANNOSE-BINDING LECTIN, Biomarkers, Tumor, LONG PENTRAXIN PTX3, Animals, Humans, RNA, Viral/blood, Antigens, SEPSIS, SARS-CoV-2, C-Reactive Protein/metabolism, Viral Load/immunology, INTERNATIONAL CONSENSUS DEFINITIONS, Critical Care/statistics & numerical data, SEPTIC SHOCK, COVID-19, Coronavirus/immunology, Antibodies, Neutralizing, Neutralizing/immunology, HEK293 Cells, Biomarkers, Tumor/metabolism, RNA, Spike Glycoprotein, Coronavirus/immunology, Biomarkers |
| Beschreibung: | Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia is associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). RNAemia is comparable in performance to the best protein predictors. Mannose binding lectin 2 and pentraxin-3 (PTX3), two activators of the complement pathway of the innate immune system, are positively associated with mortality. Machine learning identified ‘Age, RNAemia’ and ‘Age, PTX3’ as the best binary signatures associated with 28-day ICU mortality. In longitudinal comparisons, COVID-19 ICU patients have a distinct proteomic trajectory associated with mortality, with recovery of many liver-derived proteins indicating survival. Finally, proteins of the complement system and galectin-3-binding protein (LGALS3BP) are identified as interaction partners of SARS-CoV-2 spike glycoprotein. LGALS3BP overexpression inhibits spike-pseudoparticle uptake and spike-induced cell-cell fusion in vitro. |
| Publikationsart: | Article Other literature type |
| Dateibeschreibung: | application/pdf |
| Sprache: | English |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-021-23494-1 |
| DOI: | 10.17863/cam.90132 |
| Zugangs-URL: | https://www.nature.com/articles/s41467-021-23494-1.pdf https://pubmed.ncbi.nlm.nih.gov/34099652 https://hdl.handle.net/20.500.12105/23565 https://doaj.org/article/4473e05193134fe3b894751bffb9a062 https://kclpure.kcl.ac.uk/portal/en/publications/sarscov2-rnaemia-and-proteomic-trajectories-inform-prognostication-in-covid19-patients-admitted-to-intensive-care(8d565478-1e85-4136-b417-ba1f33437946).html https://www.nature.com/articles/s41467-021-23494-1 https://europepmc.org/article/MED/34099652 https://pubmed.ncbi.nlm.nih.gov/34099652/ https://www.nature.com/articles/s41467-021-23494-1.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184784/ https://kclpure.kcl.ac.uk/ws/files/153943399/SARS_CoV_2_RNAemia_and_proteomic_trajectories_inform_prognostication_in_COVID_19_patients_admitted_to_intensive_care_Nature_Communications_07.06.2021.pdf https://www.pure.ed.ac.uk/ws/files/263687109/s41467_021_23494_1.pdf https://hdl.handle.net/20.500.11820/2a4e4ea8-5731-47f9-9de4-c3457f254c5c |
| Rights: | CC BY URL: http://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) . |
| Dokumentencode: | edsair.doi.dedup.....c9b54981bd87b0451c4c66e6cc9dea4d |
| Datenbank: | OpenAIRE |
| Abstract: | Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia is associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). RNAemia is comparable in performance to the best protein predictors. Mannose binding lectin 2 and pentraxin-3 (PTX3), two activators of the complement pathway of the innate immune system, are positively associated with mortality. Machine learning identified ‘Age, RNAemia’ and ‘Age, PTX3’ as the best binary signatures associated with 28-day ICU mortality. In longitudinal comparisons, COVID-19 ICU patients have a distinct proteomic trajectory associated with mortality, with recovery of many liver-derived proteins indicating survival. Finally, proteins of the complement system and galectin-3-binding protein (LGALS3BP) are identified as interaction partners of SARS-CoV-2 spike glycoprotein. LGALS3BP overexpression inhibits spike-pseudoparticle uptake and spike-induced cell-cell fusion in vitro. |
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| ISSN: | 20411723 |
| DOI: | 10.1038/s41467-021-23494-1 |
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