Stratification of COVID-19 Severity Using SeptiCyte RAPID, a Novel Host Immune Response Test

Abstract

SeptiCyte^® RAPID is a gene expression assay measuring the relative expression levels of host response genes PLA2G7 and PLAC8, indicative of a dysregulated immune response during sepsis. As severe forms of COVID-19 may be considered viral sepsis, we evaluated SeptiCyte RAPID in a series of 94 patients admitted to Foch Hospital (Suresnes, France) with proven SARS-CoV-2 infection. EDTA blood was collected in the emergency department (ED) in 67 cases, in the intensive care unit (ICU) in 23 cases and in conventional units in 4 cases. SeptiScore (0-15 scale) increased with COVID-19 severity. Patients in ICU had the highest SeptiScores, producing values comparable to 8 patients with culture-confirmed bacterial sepsis. Receiver operating characteristic (ROC) curve analysis had an area under the curve (AUC) of 0.81 for discriminating patients requiring ICU admission from patients who were immediately discharged or from patients requiring hospitalization in conventional units. SeptiScores increased with the extent of the lung injury. For 68 patients, a chest computed tomography (CT) scan was performed within 24 h of COVID-19 diagnosis. SeptiScore >7 suggested lung injury ≥50% (AUC = 0.86). SeptiCyte RAPID was compared to other biomarkers for discriminating Critical + Severe COVID-19 in ICU, versus Moderate + Mild COVID-19 not in ICU. The mean AUC for SeptiCyte RAPID was superior to that of any individual biomarker or combination thereof. In contrast to C-reactive protein (CRP), correlation of SeptiScore with lung injury was not impacted by treatment with anti-inflammatory agents. SeptiCyte RAPID can be a useful tool to identify patients with severe forms of COVID-19 in ED, as well as during follow-up.

Keywords: COVID-19; gene expression; severity; viral sepsis.

Figure 1

Diagram of the flow of the patients in this study. (A) Sixty-seven patients sampled in ED. (B) Twenty-three patients sampled in ICU. (C) Four patients sampled by nasopharyngeal swab in the conventional unit, with subsequent SARS-CoV-2 (+) result from blood.

Figure 2

Variation of the SeptiScore in COVID-19 patients determined within 24 h after hospital admission according to the location of the patients. Comparison with SeptiScores of patients with culture-confirmed bacterial sepsis. COVID patients: Group 1—discharged within 24 h (n = 25, Figure 1A); Group 2—hospitalization in conventional unit, without subsequent admission to ICU (n = 33, Figure 1A); Group 3—transferred to ICU within 24 h (n = 16); Group 4—bacterial sepsis in ICU (n = 8).

Figure 3

SeptiCyte RAPID scores, stratified by COVID-19 severity as measured by chest CT scans within 24 h of SeptiCyte RAPID testing. (A) Stratification into critical, severe, extensive, moderate, mild, and absence groups based on chest CT scans. (B) Stratification with critical + severe combined, and moderate + mild combined.

Figure 4

Combining SeptiScore with other clinical variables. The variables CRP, D-dimer, lactate, monocytes, CD16-positive monocytes, and SeptiScore were examined alone and in combination. The patients included in this analysis were as follows: Critical + Severe in ICU (n = 11) versus Moderate + Mild not in ICU (n = 24), with only the first SeptiCyte RAPID measurement considered. The identities of the regression models are given in Supplementary Table S3. Error bars indicate the interquartile range of AUCs for 100 imputation replicates. (A) Combinations without SeptiScore. (B) Combinations with SeptiScore.

Figure 5

Hospital trajectory of patient with “critical” lung damage (male, 65 years, angor, dyslipidemia, >75% lung injury (critical), intubated with mechanical ventilation, died). In the CRP panel, the limit of detection (LoD) = 1 mg/L.