Abstract
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.
Highlights
Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19)
Demographics and clinical characteristics of COVID-19 patients. 474 blood samples were available for analysis (Fig. 1, Supplementary Fig. 1): 295 longitudinal samples from ICU patients with COVID-19 admitted to two university hospitals (GSTT; n = 62 and King’s College Hospital (KCH); n = 16) and samples from hospitalized, non-ICU COVID-19 patients for comparison (n = 45); ICU and non-ICU patients without COVID-19 served as controls (n = 55)
The primary outcome measure was defined as mortality 28 days after ICU admission
Summary
Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). It is increasingly apparent that conventional prognostic scores for patients admitted to intensive care units (ICUs) such as the Acute Physiology and Chronic Health Evaluation (APACHE II) score[1] and Sequential Organ Failure Assessment (SOFA) score[2], are unsuitable for outcome prediction in COVID-19 ICU patients[3,4,5,6] In this context, circulating SARS-CoV-2 RNA (RNAemia) has been highlighted as a promising prognostic marker in hospitalized COVID-19 patients, as it is associated with disease severity[7] and mortality[8,9,10], with an estimated prevalence of 10% (95% CI: 5–18%, random-effects model)[7]. In the context of RNAemia, we explored the plasma protein interactions with the SARS-CoV-2 spike glycoprotein, identifying galectin-3-binding protein (LGALS3BP) as a novel binding partner with antiviral activities
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