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

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-021-23494-1

2041-1723

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

COVID-19 diagnosis using AI

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.