A dynamic mucin mRNA signature associates with COVID-19 disease presentation and severity
Annemieke Smet, … , Philippe G. Jorens, Benedicte Y. De Winter
Annemieke Smet, … , Philippe G. Jorens, Benedicte Y. De Winter
Published August 27, 2021
Citation Information: JCI Insight. 2021;6(19):e151777. https://doi.org/10.1172/jci.insight.151777.
View: Text | PDF
Clinical Research and Public Health COVID-19

A dynamic mucin mRNA signature associates with COVID-19 disease presentation and severity

Abstract

BACKGROUND SARS-CoV-2 infection induces mucin overexpression, further promoting disease. Given that mucins are critical components of innate immunity, unraveling their expression profiles that dictate the course of disease could greatly enhance our understanding and management of COVID-19.METHODS Using validated RT-PCR assays, we assessed mucin mRNA expression in the blood of patients with symptomatic COVID-19 compared with symptomatic patients without COVID-19 and healthy controls and correlated the data with clinical outcome parameters. Additionally, we analyzed mucin expression in mucus and lung tissue from patients with COVID-19 and investigated the effect of drugs for COVID-19 treatment on SARS-CoV-2–induced mucin expression in pulmonary epithelial cells.RESULTS We identified a dynamic blood mucin mRNA signature that clearly distinguished patients with symptomatic COVID-19 from patients without COVID-19 based on expression of MUC1, MUC2, MUC4, MUC6, MUC13, MUC16, and MUC20 (AUCROC of 91.8%; sensitivity and specificity of 90.6% and 93.3%, respectively) and that discriminated between mild and critical COVID-19 based on the expression of MUC16, MUC20, and MUC21 (AUCROC of 89.1%; sensitivity and specificity of 90.0% and 85.7%, respectively). Differences in the transcriptional landscape of mucins in critical cases compared with mild cases identified associations with COVID-19 symptoms, respiratory support, organ failure, secondary infections, and mortality. Furthermore, we identified different mucins in the mucus and lung tissue of critically ill COVID-19 patients and showed the ability of baricitinib, tocilizumab, favipiravir, and remdesivir to suppress expression of SARS-CoV-2–induced mucins.CONCLUSION This multifaceted blood mucin mRNA signature showed the potential role of mucin profiling in diagnosing, estimating severity, and guiding treatment options in patients with COVID-19.FUNDING The Antwerp University Research and the Research Foundation Flanders COVID-19 funds.

Authors

Annemieke Smet, Tom Breugelmans, Johan Michiels, Kevin Lamote, Wout Arras, Joris G. De Man, Leo Heyndrickx, Anne Hauner, Manon Huizing, Surbhi Malhotra-Kumar, Martin Lammens, An Hotterbeekx, Samir Kumar-Singh, Aline Verstraeten, Bart Loeys, Veronique Verhoeven, Rita Jacobs, Karolien Dams, Samuel Coenen, Kevin K. Ariën, Philippe G. Jorens, Benedicte Y. De Winter

×

Figure 5

Peripheral mucin mRNA expression levels as variables associated with COVID-19 severity and presentation.

Options: View larger image (or click on image) Download as PowerPoint
Peripheral mucin mRNA expression levels as variables associated with COV...
(A) ROC curve and AUC for the prediction model of COVID-19 severity, i.e., critical COVID-19 (n = 50) or mild COVID-19 (n = 35) obtained by LASSO logistic regression. Included predictors were age and mRNA expression of MUC16, MUC20, and MUC21, with an AUC of 89.1% (95% CI: 80.4%–96.1%), a sensitivity of 90.0% (95% CI: 79.3%–96.2%), and a specificity of 85.7% (95% CI: 71.2%–94.6%). (B) ROC curve and AUC for the prediction model of COVID-19 presentation: COVID-19 positive (n = 85) or COVID-19 negative (n = 30) obtained by the LASSO logistic regression. Included predictors were age and mRNA expression of MUC1, MUC2, MUC4, MUC6, MUC13, MUC16, and MUC20, with an AUC of 91.8% (95% CI: 85.2%–97.1%), a sensitivity of 90.6% (95% CI: 83.0%–95.5%), and a specificity of 93.3% (95% CI: 79.7%–98.9%).