SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care
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Published:2021-06-07
Issue:1
Volume:12
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Gutmann ClemensORCID, Takov KaloyanORCID, Burnap Sean A.ORCID, Singh BhawanaORCID, Ali Hashim, Theofilatos KonstantinosORCID, Reed Ella, Hasman Maria, Nabeebaccus Adam, Fish MatthewORCID, McPhail Mark JW., O’Gallagher Kevin, Schmidt Lukas E.ORCID, Cassel Christian, Rienks MariekeORCID, Yin XiaokeORCID, Auzinger Georg, Napoli Salvatore, Mujib Salma F., Trovato Francesca, Sanderson BarnabyORCID, Merrick BlairORCID, Niazi UmarORCID, Saqi Mansoor, Dimitrakopoulou Konstantina, Fernández-Leiro RafaelORCID, Braun SilkeORCID, Kronstein-Wiedemann Romy, Doores Katie J.ORCID, Edgeworth Jonathan D., Shah Ajay M., Bornstein Stefan R.ORCID, Tonn TorstenORCID, Hayday Adrian C.ORCID, Giacca MauroORCID, Shankar-Hari ManuORCID, Mayr ManuelORCID
Abstract
AbstractPrognostic 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.
Funder
British Heart Foundation Fondation Leducq
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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