A 9-mRNA signature measured from whole blood by a prototype PCR panel predicts 28-day mortality upon admission of critically ill COVID-19 patients

Abstract

Immune responses affiliated with COVID-19 severity have been characterized and associated with deleterious outcomes. These approaches were mainly based on research tools not usable in routine clinical practice at the bedside. We observed that a multiplex transcriptomic panel prototype termed Immune Profiling Panel (IPP) could capture the dysregulation of immune responses of ICU COVID-19 patients at admission. Nine transcripts were associated with mortality in univariate analysis and this 9-mRNA signature remained significantly associated with mortality in a multivariate analysis that included age, SOFA and Charlson scores. Using a machine learning model with these 9 mRNA, we could predict the 28-day survival status with an Area Under the Receiver Operating Curve (AUROC) of 0.764. Interestingly, adding patients’ age to the model resulted in increased performance to predict the 28-day mortality (AUROC reaching 0.839). This prototype IPP demonstrated that such a tool, upon clinical/analytical validation and clearance by regulatory agencies could be used in clinical routine settings to quickly identify patients with higher risk of death requiring thus early aggressive intensive care.

Differentiation of COVID-19 from other emergency infectious disease presentations using whole blood transcriptomics then rapid qPCR: a case-control and observational cohort study

“…A number of investigators have applied whole blood transcriptomics to identify predictive scores for deterioration in COVID-19 (20,(22)(23)(24)(25)(26). We did not attempt this in our cohort as the number of COVID-19 patient RNA samples that successfully underwent RNA-seq was relatively small (n=88) and all stemmed from the first (Wuhan) wave of COVID-19, prior to specific treatments being available, with limited access to intensive care or non-invasive ventilation, and at a time when inpatient mortality was very high, just under 30%.…”

“…Host blood transcriptomic signatures are well-recognised for their ability to differentiate infections based on aetiology, severity and even symptomatology (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(20)(21)(22)(23)(24)(25). Although there are useful existing gene expression signatures that can differential acute viral infections from bacterial sepsis, more granular differentiation of COVID-19 from other viral infections such as influenza, RSV, or rhinovirus may be crucial to ongoing patient management, both in terms of infection control decisions as well as treatment.…”

Joint modeling of monocyte HLA‐DR expression trajectories predicts 28‐day mortality in severe SARS‐CoV‐2 patients

“…Between March 2020 and May 2022, critically ill patients admitted to five ICUs from Lyon academic hospitals (Hospices Civils de Lyon, Lyon, France) who presented with pulmonary infection with SARS‐CoV‐2 were prospectively included in RICO clinical study. Preliminary results from subgroups of the cohort were published previously 12–16 . This study was approved by an ethics committee (Comité de Protection des Personnes Ile de France 1 – N°IRB/IORG #: IORG0009918) under agreement number 2020‐A01079‐30.…”

“…Preliminary results from subgroups of the cohort were published previously. 12 , 13 , 14 , 15 , 16 This study was approved by an ethics committee (Comité de Protection des Personnes Ile de France 1 – N°IRB/IORG #: IORG0009918) under agreement number 2020‐A01079‐30. This clinical study was registered at ClinicalTrials.gov (NCT04392401).…”