Journal Article

Identification of two early blood biomarkers ACHE and CLEC12A for improved risk stratification of critically ill COVID-19 patients

Sylvester, Caroline, Brenner, Thorsten, Glanz, Karolina, Manoochehri, Mehdi, Sohn, Kai, Kattner, Simone, Berger, Marc Moritz, Müller, Jan, Vainshtein, Yevhen

2023

Overview

In order to identify biomarkers for earlier prediction of COVID-19 outcome, we collected blood samples from patients with fatal outcomes (non-survivors) and with positive clinical outcomes (survivors) at ICU admission and after seven days. COVID-19 survivors and non-survivors showed significantly different transcript levels for 93 genes in whole blood already at ICU admission as revealed by RNA-Seq. These differences became even more pronounced at day 7, resulting in 290 differentially expressed genes. Many identified genes play a role in the differentiation of hematopoietic cells. For validation, we designed an RT-qPCR assay for C-type lectin domain family 12 member A ( CLEC12A ) and acetylcholinesterase ( ACHE ), two transcripts that showed highest potential to discriminate between survivors and non-survivors at both time points. Using our combined RT-qPCR assay we examined 33 samples to accurately predict patient survival with an AUROC curve of 0.931 (95% CI = 0.814–1.000) already at ICU admission. CLEC12A and ACHE showed improved prediction of patient outcomes compared to standard clinical biomarkers including CRP and PCT in combination (AUROC = 0.403, 95% CI = 0.108–0.697) or SOFA score (AUROC = 0.701 95% CI = 0.451–0.951) at day 0. Therefore, analyzing CLEC12A and ACHE gene expression from blood may provide a promising approach for early risk stratification of severely ill COVID-19 patients.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/337/2019 / 692/308/53/2423 / Acetylcholinesterase / Biomarkers / Blood / Cell differentiation / Coronaviruses / COVID-19 / COVID-19 - genetics / Critical Illness / Gene expression / Hematopoietic stem cells / Humanities and Social Sciences / Humans / Intensive Care Units / Lectins, C-Type - genetics / multidisciplinary / Organ Dysfunction Scores / Patients / Prognosis / Receptors, Mitogen / Retrospective Studies / Risk Assessment / ROC Curve / Science / Science (multidisciplinary)