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. Here the authors use RT-qPCR and mass spectrometry to analyze longitudinal blood samples from intensive care unit (ICU) COVID-19 patients and controls. They find that viral RNA and pentraxin-3 predict 28-day ICU mortality and that galectin-3-binding protein is an interaction partner of SARS-CoV-2 spike glycoprotein with antiviral properties.
【저자키워드】 SARS-CoV-2, mass spectrometry, Prognostic markers, 【초록키워드】 COVID-19, coronavirus disease, severe acute respiratory syndrome coronavirus 2, Coronavirus disease 2019, coronavirus, mass spectrometry, Mortality, intensive care, complement system, machine learning, Antibody Response, spike glycoprotein, intensive care unit, Sepsis, complement, predictors, in vitro, severe acute respiratory syndrome Coronavirus, ICU, RNA, innate immune system, risk stratification, Protein, serum, RT-qPCR, survival, Viral, Characteristics, SARS-CoV-2 spike glycoprotein, Patient, galectin-3, trajectory, plasma, ICU Patients, Viral RNA, cell-cell fusion, respiratory, predict, proteomic, Neutralizing antibody response, binding, hospitalized COVID-19 patient, COVID-19 patient, best, Non-COVID-19, Complement pathway, acute respiratory syndrome, hospitalized COVID-19 patients, acute respiratory syndrome coronavirus, Blood samples, healthy control, hazard ratio, blood sample, Comparisons, antiviral properties, mannose, healthy controls, machine, overexpression, Ptx3, interaction partner, LGALS3BP, controls, ICU patient, inhibit, adjusted, comparable, age and sex, sepsis patient, 【제목키워드】 intensive care, trajectory, proteomic, COVID-19 patient,