Evaluation of the host immune response assay SeptiCyte RAPID for potential triage of COVID-19 patients

Abstract

Tools for the evaluation of COVID-19 severity would help clinicians with triage decisions, especially the decision whether to admit to ICU. The aim of this study was to evaluate SeptiCyte RAPID, a host immune response assay (Immunexpress, Seattle USA) as a triaging tool for COVID-19 patients requiring hospitalization and potentially ICU care. SeptiCyte RAPID employs a host gene expression signature consisting of the ratio of expression levels of two immune related mRNAs, PLA2G7 and PLAC8, measured from whole blood samples. Blood samples from 146 adult SARS-CoV-2 (+) patients were collected within 48 h of hospital admission in PAXgene blood RNA tubes at Hospital del Mar, Barcelona, Spain, between July 28th and December 1st, 2020. Data on demographics, vital signs, clinical chemistry parameters, radiology, interventions, and SeptiCyte RAPID were collected and analyzed with bioinformatics methods. The performance of SeptiCyte RAPID for COVID-19 severity assessment and ICU admission was evaluated, relative to the comparator of retrospective clinical assessment by the Hospital del Mar clinical care team. In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity: critical vs. mild (AUC = 0.93, p < 0.0001), critical vs. moderate (AUC = 0.77, p = 0.002), severe vs. mild (AUC = 0.85, p = 0.0003), severe vs. moderate (AUC = 0.63, p = 0.05). This discrimination was significantly better (by AUC or p-value) than could be achieved by CRP, lactate, creatine, IL-6, or D-dimer. Some of the critical or severe cases had "early" blood draws (before ICU admission; n = 33). For these cases, when compared to moderate and mild cases not in ICU (n = 37), SeptiCyte RAPID had AUC = 0.78 (p = 0.00012). In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity as defined by the WHO COVID-19 Clinical Management Living Guidance of January 25th, 2021. Measurements taken early (before a patient is considered for ICU admission) suggest that high SeptiScores could aid in predicting the need for later ICU admission.

Figure 1

Principal Component Analysis (PCA) biplot, for separation of patients with ICU admission vs. non-admission. A total of 45 variables were used to define the dimensions (“eigenvectors”) of the PCA plot. A total of n = 77 patients were analyzed, representing critical and severe COVID cases that needed ICU admission (red points; N = 40) vs. mild and moderate cases that did not need ICU admission (black points; N = 37). These were the two maximally different groups within the study cohort. The variables shown with blue dotted arrows are supplementary continuous variables which did not contribute to the construction of the PCA dimensions, but which are presented to aid in the interpretation in the PCA biplot. Additional details are provided in Supplementary Table 3.

Figure 2

(A) SeptiCyte RAPID scores across the COVID-19 severity categories defined in the WHO COVID-19 Guidance 2021, as assessed by the clinical care team at Hospital del Mar (n = 146). (B) SeptiCyte RAPID scores across the COVID-19 severity categories, after further stratification by ICU admission vs. non-admission. (C) SeptiCyte RAPID scores for differentiating COVID patients that needed ICU admission from the cases that did not need ICU admission.

Figure 3

Performance of SeptiCyte RAPID relative to IL-6, in discriminating COVID severities. Panel A: distribution of SeptiScores across the different COVID severity classes (n = 77; only those patients who also had IL-6 measurements were considered). Panel B: IL-6 levels in pg/ml, log2 transformed, for patients across the same severity classes (n = 77; all available data). Panel C: SeptiCyte RAPID for mild + moderate grouped together, vs. critical + severe grouped together. Panel D: IL-6 for mild + moderate grouped together, vs. critical + severe grouped together.

Figure 4

Predicting ICU admission using SeptiCyte RAPID (n = 146).

Figure 5

SeptiScore stratified by type of oxygen therapy closest to blood draw. A total of 146 patients are represented in this plot.