TY - JOUR
AU - Gutmann, Clemens
AU - Takov, Kaloyan
AU - Burnap, Sean A
AU - Singh, Bhawana
AU - Ali, Hashim
AU - Theofilatos, Konstantinos
AU - Reed, Ella
AU - Hasman, Maria
AU - Nabeebaccus, Adam
AU - Fish, Matthew
AU - McPhail, Mark J.W.
AU - O'Gallagher, Kevin
AU - Schmidt, Lukas E
AU - Cassel, Christian
AU - Rienks, Marieke
AU - Yin, Xiaoke
AU - Auzinger, Georg
AU - Napoli, Salvatore
AU - Mujib, Salma F
AU - Trovato, Francesca
AU - Sanderson, Barnaby
AU - Merrick, Blair
AU - Niazi, Umar
AU - Saqi, Mansoor
AU - Dimitrakopoulou, Konstantina
AU - Fernández-Leiro, Rafael
AU - Braun, Silke
AU - Kronstein-Wiedemann, Romy
AU - Doores, Katie J.
AU - Edgeworth, Jonathan D.
AU - Shah, Ajay M
AU - Bornstein, Stefan R
AU - Tonn, Torsten
AU - Hayday, Adrian C
AU - Giacca, Mauro
AU - Shankar-Hari, Manu
AU - Mayr, Manuel
PY - 2021
DA - June
TI - SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care
JO - Nature Communications
VL - 12
IS - 1
DO - https://doi.org/10.1038/s41467-021-23494-1
AB - 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.
PB - Elsevier
UR - https://www.research.ed.ac.uk/en/publications/2a4e4ea8-5731-47f9-9de4-c3457f254c5c
KW - Coronavirus (COVID-19)
ER