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.

Organ-Dysfunction Markers in Mild-to-Moderate COVID-19 Convalescents

“…Its activity leads to the release of several proinflammatory agents that contribute to endothelial damage and atherosclerosis [30]. The majority of published studies indicate that patients infected with SARS-CoV-2, especially those with a severe course of the disease, express an increased concentration of Lp-PLA2 [31][32][33]. Lp-PLA2 has also been considered to be a prognostic marker for the course of COVID-19 [10].…”

Diagnostic Accuracy of Septicyte Rapid to Discriminate Sepsis From Sterile Inflammation in Patients Meeting Sepsis Criteria According to Sepsis-3 Definition at ICU Admission

“…Since SeptiCyte® RAPID scores are based on gene activation, the SeptiScore value depends on the presence of an invasive infection and is not affected by disease severity. In contrast, two recent studies [25,26] have described the ability of SeptiCyte® RAPID to stratify COVID-19 cases according to clinical severity by predicting the need for ICU admission. In all probability, the in ammatory response associated with COVID-19 patients is different from the response in bacterial sepsis [27,28].…”

Plac8-ERK pathway modulation of monocyte function in sepsis

“…Inflammation is a complex process involving multiple signaling pathways and cell types, and balancing pro-inflammatory and anti-inflammatory signals is crucial [ 43 , 44 ]. However, further exploration is needed to understand how Plac8 maintains this balance in sepsis, which could have important implications for developing new treatment strategies [ 24 ].…”

“…Preliminary research indicates that Plac8 plays a role in the regulation of immune cell functions; however, the exact mechanism by which it operates in this capacity is not fully comprehended [ 22 , 23 ]. The involvement of this protein in autophagy, cell cycle control, and apoptosis implies its potential key role in sepsis pathogenesis [ 24 ]. Particularly in the context of monocytes, understanding how Plac8 influences their activity by modulating intracellular signaling is crucial [ 23 , 25 ].…”