Prognostic peripheral blood biomarkers at ICU admission predict COVID-19 clinical outcomes.

The COVID-19 pandemic continues to challenge the capacities of hospital ICUs which currently lack the ability to identify prospectively those patients who may require extended management. In this study of 90 ICU COVID-19 patients, we evaluated serum levels of four cytokines (IL-1ß, IL-6, IL-10 and TNFα) as well as standard clinical and laboratory measurements. On 42 of these patients (binned into Initial and Replication Cohorts), we further performed CyTOF-based deep immunophenotyping of peripheral blood mononuclear cells with a panel of 38 antibodies. All measurements and patient samples were taken at time of ICU admission and retrospectively linked to patient clinical outcomes through statistical approaches. These analyses resulted in the definition of a new measure of patient clinical outcome: patients who will recover after short ICU stays (< 6 days) and those who will subsequently die or recover after long ICU stays (≥6 days). Based on these clinical outcome categories, we identified blood prognostic biomarkers that, at time of ICU admission, prospectively distinguish, with 91% sensitivity and 91% specificity (positive likelihood ratio 10.1), patients in the two clinical outcome groups. This is achieved through a tiered evaluation of serum IL-10 and targeted immunophenotyping of monocyte subsets, specifically, CD11clow classical monocytes. Both immune biomarkers were consistently elevated ( ≥15 pg/ml and ≥2.7 x107/L for serum IL-10 and CD11clow classical monocytes, respectively) in those patients who will subsequently die or recover after long ICU stays. This highly sensitive and specific prognostic test could prove useful in guiding clinical resource allocation.

The Utility of Blood Based Biomarkers in Detecting Neurological Complications of COVID‐19 in Critically Ill Patients

Background Neurological and neuropsychiatric complications have been documented in patients with COVID‐19. This study aims to investigate the utility of two neurological blood‐based biomarkers to predict neurological complications and mortality due to COVID‐19 in the intensive care unit (ICU). Neurofilament light (NF‐L) is a marker of axonal damage and glial fibrillary acidic protein (GFAP) is a marker of astrocytic activation. Methods Patients with respiratory failure were prospectively enrolled from the ICU at Vancouver General Hospital. COVID‐19 patients were excluded if the diagnosis was an incidental secondary finding upon ICU admission or if their enrollment was >10 days after ICU admission. Control patients were excluded if their enrollment was >4 days after ICU admission or if their primary diagnosis was non‐respiratory. Plasma samples were collected upon admission study enrollment, with additional samples collected on day 7 and day 14 from COVID‐19 patients. Plasma NF‐L and GFAP were quantified using the Quanterix Simoa HD‐X analyzer. Group comparisons were performed using a Mann‐Whitney test. Trajectory analysis was performed using a Wilcoxon test or Friedman one‐way ANOVA. Area under receiver operating curve (AUROC) analysis was calculated to predict neurological complications and mortality during ICU stay. Results Of the 242 patients enrolled, 209 were confirmed positive for SARS‐CoV‐2 while 33 served as ICU controls. Median age was 61 years for the COVID‐19 group, 64 years for controls. Upon ICU admission, NF‐L was 32% lower and GFAP was 24% lower in those with COVID‐19 compared to controls after correcting for age. NF‐L concentrations increase by doubling each week of ICU stay, while GFAP remained stable. Over the course of their ICU stay, 16% COVID‐19 patients were diagnosed with a neurological complication and 17% died. Plasma NF‐L and GFAP demonstrated a moderate to strong ability to predict neurological complications (AUROC: NF‐L=0.702;GFAP=0.722) and mortality (AUROC: NF‐L=0.815;GFAP=0.809) during ICU stay. Conclusions Upon ICU admission, NF‐L and GFAP were lower in patients with COVID‐19 compared to controls. NF‐L, but not GFAP, increased over the course of ICU stay in patients with COVID‐19. Both markers were able to predict neurological complication or ICU mortality with moderate to strong accuracy.

Prognostic peripheral blood biomarkers at ICU admission predict COVID-19 clinical outcomes

The COVID-19 pandemic continues to challenge the capacities of hospital ICUs which currently lack the ability to identify prospectively those patients who may require extended management. In this study of 90 ICU COVID-19 patients, we evaluated serum levels of four cytokines (IL-1β, IL-6, IL-10 and TNFα) as well as standard clinical and laboratory measurements. On 42 of these patients (binned into Initial and Replication Cohorts), we further performed CyTOF-based deep immunophenotyping of peripheral blood mononuclear cells with a panel of 38 antibodies. All measurements and patient samples were taken at time of ICU admission and retrospectively linked to patient clinical outcomes through statistical approaches. These analyses resulted in the definition of a new measure of patient clinical outcome: patients who will recover after short ICU stays (< 6 days) and those who will subsequently die or recover after long ICU stays (≥6 days). Based on these clinical outcome categories, we identified blood prognostic biomarkers that, at time of ICU admission, prospectively distinguish, with 91% sensitivity and 91% specificity (positive likelihood ratio 10.1), patients in the two clinical outcome groups. This is achieved through a tiered evaluation of serum IL-10 and targeted immunophenotyping of monocyte subsets, specifically, CD11clow classical monocytes. Both immune biomarkers were consistently elevated ( ≥15 pg/ml and ≥2.7 x107/L for serum IL-10 and CD11clow classical monocytes, respectively) in those patients who will subsequently die or recover after long ICU stays. This highly sensitive and specific prognostic test could prove useful in guiding clinical resource allocation.