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Introduction

COVID-19 mortality is highly associated with sepsis [1]. SeptiCyte® RAPID is a CEmarked, cartridge-based, sample-to-answer gene expression assay in whole blood for assessing the probability of sepsis [2]. The test result (SeptiScore®) is reported as a value (0 to 15) in three interpretation bands, representing an increase in the risk of sepsis (Figure 1). Results are available within approximately 1 hour directly from blood samples, supporting its use in the risk stratification of COVID-19 patients. The objective of this study was to examine the utility of SeptiCyte® RAPID to assess the early recognition of viral sepsis and the subsequent risk of ICU admission in patients hospitalized with COVID-19.

METHODS

Patient samples (n=113) from COVID-19(+) cases were obtained within two days of hospital admission, after informed consent as part of a retrospective cohort collected at Hospital del Mar, Barcelona, Spain, between, July 28th – December 1st, 2020. The demographics of this cohort were: 47 (42%) Female, 66 (58%) Male, Age: 26-95 (IQR 54-75), 18 (16%) Asian, 78 (69%) White, 2 (2%) Black and 15 (13%) race not recorded. Clinical data was collected during patient standard of care and COVID-19 disease severity assessments were provided by the care team at Hospital del Mar. Patients were stratified into Critical, Severe, Moderate and Mild categories (Table 1) based on their COVID-19 disease clinical characteristics (Table 2). PAXgene® blood samples were tested with SeptiCyte® RAPID on the Biocartis Idylla™ platform. METHODS As shown in Figure 2, SeptiCyte® RAPID discriminated critical/severe (n=86) COVID-19 from moderate/mild (n=27) cases with an AUROC (area under a receiver operating characteristic curve) of 0.73. Test result values above a threshold value of 7.4 were highly specific (specificity = 85%) for critical/severe COVID-19. Test results were also predictive of ICU admission (AUROC = 0.77) in critical/severe COVID-19 cases (n=29) that needed ICU admission following blood draw relative to mild/ moderate cases (n=27) that were not admitted to ICU (Figure 3). Band 3 results maintain high specificity (85%) in predicting patients that require an escalation in care. Severe patients that did not progress to ICU admission were excluded from this analysis. SeptiCyte® RAPID outperformed commonly used clinical lab tests (Table 3) for COVID-19 patient management, including D-dimer and IL6 (p-value ≤ 0.05).

RESULTS

As shown in Figure 2, SeptiCyte® RAPID discriminated critical/severe (n=86) COVID-19 from moderate/mild (n=27) cases with an AUROC (area under a receiver operating characteristic curve) of 0.73. Test result values above a threshold value of 7.4 were highly specific (specificity = 85%) for critical/severe COVID-19. Test results were also predictive of ICU admission (AUROC = 0.77) in critical/severe COVID-19 cases (n=29) that needed ICU admission following blood draw relative to mild/ moderate cases (n=27) that were not admitted to ICU (Figure 3). Band 3 results maintain high specificity (85%) in predicting patients that require an escalation in care. Severe patients that did not progress to ICU admission were excluded from this analysis. SeptiCyte® RAPID outperformed commonly used clinical lab tests (Table 3) for COVID-19 patient management, including D-dimer and IL6 (p-value ≤ 0.05).

CONCLUSION

Early (within 48 hours of admission) SeptiScore® values:
– Differentiate critical/severe COVID 19 disease from mild/moderate disease
– Correlate with need for ICU level care

The SeptiScore® provided a statistically and clinically more accurate prediction of the risk of critical or severe COVID 19 disease than IL6

FIGURES

Figure 1

SeptiCyte® RAPID quantifies specific host immune genes to enable early identification of infection in suspected sepsis patients.

Figure 2

Increases in the SeptiCyte® RAPID test result (SeptiScore®) correlates with COVID-19 severity. Test results in Band 3 (>7.4) had high specificity (0.85) for critical/severe COVID-19 when compared to moderate/mild cases (p < 0.001).

Figure 3

SeptiCyte® RAPID results were predictive of subsequent ICU admission (AUC = 0.77, p < 0.005) for critical/severe patients (n=29) when compared to moderate/mild COVID-19 patients (n=27).

TABLES

Table 1

Scale and rating system employed by the study investigators to determine patient COVID-19 disease severity and alignment with WHO clinical management guidelines.

Table 2

Clinical characteristics of COVID-19 study patients.

Table 3

SeptiCyte® RAPID  performance compared to common lab parameters for the discrimination of critical/severe from moderate/mild COVID-19.

AUTHORS

Max Hardy-Werbin1,2, Soledad Gonzalez Gallardo2, Erica Torres3, Rebeca Rueda3, Irene Hannet4, James Kirk4, Thomas Yager4, Krupa Navalkar4, Maria del Mar Arenas2,5, Itziar Arrieta-Aldea2,5, Silvia Castañeda2,5, Joan Gómez-Junyent2,5, Silvia Gómez-Zorrilla2,5, Roberto Guerri2,5, Juan Pablo Horcajada2,5, Emili Letang2,5, Immaculada López-Montesinos2,5, Milagro Montero2,5, Ivan Pelegrín2,5, Elena Sendra2,5, Luisa Sorlí2,5, Judit Villar-García2,5, Beatriz Bellosillo2,3

1 Emergency Department, Hospital del Mar, Barcelona Spain, 2Hospital del Mar Medical Research Institute, Hospital del Mar, Barcelona Spain, 3Pathology Department, Hospital del Mar, Barcelona Spain 4Immunexpress, Seattle WA USA, 5Infectious Disease Department, COVID-MAR group, Hospital del Mar, Barcelona Spain

REFERENCES

[1] Chen et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ 2020; 368:m1091. doi: 10.1136/bmj.m1091. [2] Kirk et al. Clinical performance of a rapid sepsis test on a near-patient molecular testing platform. eISICEM 2020 #P481.

ACKNOWLEDGMENTS

This project has been supported in whole or in part by the Biomedical Advanced Research and Development Authority (BARDA), part of the HHS Office of the Assistant Secretary for Preparedness and Response under Contract No. 75A50120C00125.