Decreased GLUT1/NHE1 RNA expression in whole blood predicts disease severity in patients with COVID-19.

Abstract

AIMS:

We aimed to assess whether expression of whole-blood RNA of sodium proton exchanger 1 (NHE1) and glucose transporter 1 (GLUT1) is associated with COVID-19 infection and outcome in patients presenting to the emergency department with respiratory infections. Furthermore, we investigated NHE1 and GLUT1 expression in the myocardium of deceased COVID-19 patients.

METHODS AND RESULTS:

Whole-blood quantitative assessment of NHE1 and GLUT1 RNA was performed using quantitative PCR in patients with respiratory infection upon first contact in the emergency department and subsequently stratified by SARS-CoV-2 infection status. Assessment of NHE1 and GLUT1 RNA using PCR was also performed in left ventricular myocardium of deceased COVID-19 patients. NHE1 expression is up-regulated in whole blood of patients with COVID-19 compared with other respiratory infections at first medical contact in the emergency department (control: 0.0021 ± 0.0002, COVID-19: 0.0031 ± 0.0003, P = 0.01). The ratio of GLUT1 to NHE1 is significantly decreased in the blood of COVID-19 patients who are subsequently intubated and/or die (severe disease) compared with patients with moderate disease (moderate disease: 0.497 ± 0.083 vs. severe disease: 0.294 ± 0.0336, P = 0.036). This ratio is even further decreased in the myocardium of patients who deceased from COVID-19 in comparison with the myocardium of non-infected donors.

CONCLUSIONS:

NHE1 and GLUT1 may be critically involved in the disease progression of SARS-CoV-2 infection. We show here that SARS-CoV-2 infection critically disturbs ion channel expression in the heart. A decreased ratio of GLUT1/NHE1 could potentially serve as a biomarker for disease severity in patients with COVID-19.

• Authors: Julian Mustroph, Julian Hupf, Frank Hanses, Katja Evert, Maria J Baier, Matthias Evert, Christine Meindl, Stefan Wagner, Ute Hubauer, Gabriela Pietrzyk, Simon Leininger, Stephan Staudner, Manuel Vogel, Stefan Wallner, Markus Zimmermann, Samuel Sossalla, Lars S Maier, Carsten Jungbauer
• Journal: ESC heart failure (ESC Heart Fail) Vol. 8 Issue 1 Pg. 309-316 (02 2021) ISSN: 2055-5822 [Electronic] England
• PMID: 33215884 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Chemical References

• Glucose Transporter Type 1
• RNA, Messenger
• SLC2A1 protein, human
• SLC9A1 protein, human
• Sodium-Hydrogen Exchanger 1

Topics

• COVID-19 (blood, diagnosis, metabolism)
• Case-Control Studies
• Emergency Service, Hospital
• Female
• Glucose Transporter Type 1 (blood, metabolism)
• Humans
• Male
• Middle Aged
• Polymerase Chain Reaction
• Predictive Value of Tests
• Prospective Studies
• RNA, Messenger (blood)
• Severity of Illness Index
• Sodium-Hydrogen Exchanger 1 (blood, metabolism)