SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care

Clemens Gutmann, Kaloyan Takov, Sean A Burnap, Bhawana Singh, Hashim Ali, Konstantinos Theofilatos, Ella Reed, Maria Hasman, Adam Nabeebaccus, Matthew Fish, Mark Jw McPhail, Kevin O'Gallagher, Lukas E Schmidt, Christian Cassel, Marieke Rienks, Xiaoke Yin, Georg Auzinger, Salvatore Napoli, Salma F Mujib, Francesca TrovatoBarnaby Sanderson, Blair Merrick, Umar Niazi, Mansoor Saqi, Konstantina Dimitrakopoulou, Rafael Fernández-Leiro, Silke Braun, Romy Kronstein-Wiedemann, Katie J Doores, Jonathan D Edgeworth, Ajay M Shah, Stefan R Bornstein, Torsten Tonn, Adrian C Hayday, Mauro Giacca, Manu Shankar-Hari, Manuel Mayr

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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.

Original languageEnglish
Article number3406
JournalNature Communications
Issue number1
Publication statusPublished - Dec 2021


  • Adult
  • Animals
  • Antibodies, Neutralizing/immunology
  • Antigens, Neoplasm/metabolism
  • Biomarkers, Tumor/metabolism
  • C-Reactive Protein/metabolism
  • COVID-19/metabolism
  • Critical Care/statistics & numerical data
  • Female
  • HEK293 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proteomics/methods
  • RNA, Viral/blood
  • SARS-CoV-2/genetics
  • Serum Amyloid P-Component/metabolism
  • Spike Glycoprotein, Coronavirus/immunology
  • Viral Load/immunology


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