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

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

doi:10.1172/jci.insight.151777

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

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 AriënPhilippe G Jorens, Benedicte Y De Winter

Virology

Research output: Contribution to journal › A1: Web of Science-article › peer-review

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Abstract

BACKGROUNDSARS-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.METHODSUsing 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.RESULTSWe 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.CONCLUSIONThis 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.FUNDINGThe Antwerp University Research and the Research Foundation Flanders COVID-19 funds.

Original language	English
Article number	e151777
Journal	JCI insight
Volume	6
Issue number	19
ISSN	2379-3708
DOIs	https://doi.org/10.1172/jci.insight.151777
Publication status	Published - 2021

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2021jinse151777Final published version, 3.26 MBLicence: CC BY

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Smet, A., Breugelmans, T., Michiels, J., Lamote, K., Arras, W., De Man, J. G., Heyndrickx, L., Hauner, A., Huizing, M., Malhotra-Kumar, S., Lammens, M., Hotterbeekx, A., Kumar-Singh, S., Verstraeten, A., Loeys, B., Verhoeven, V., Jacobs, R., Dams, K., Coenen, S., ... De Winter, B. Y. (2021). A dynamic mucin mRNA signature associates with COVID-19 disease presentation and severity. JCI insight, 6(19), Article e151777. https://doi.org/10.1172/jci.insight.151777

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title = "A dynamic mucin mRNA signature associates with COVID-19 disease presentation and severity",

abstract = "BACKGROUNDSARS-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.METHODSUsing 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.RESULTSWe 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.CONCLUSIONThis 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.FUNDINGThe Antwerp University Research and the Research Foundation Flanders COVID-19 funds.",

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

note = "FTX; DOAJ; (CC BY 4.0)",

year = "2021",

doi = "10.1172/jci.insight.151777",

language = "English",

volume = "6",

journal = "JCI insight",

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publisher = "The American Society for Clinical Investigation",

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Smet, A, Breugelmans, T, Michiels, J, Lamote, K, Arras, W, De Man, JG, Heyndrickx, L , Hauner, A, Huizing, M, Malhotra-Kumar, S, Lammens, M, Hotterbeekx, A, Kumar-Singh, S, Verstraeten, A, Loeys, B, Verhoeven, V, Jacobs, R, Dams, K, Coenen, S, Ariën, KK, Jorens, PG & De Winter, BY 2021, 'A dynamic mucin mRNA signature associates with COVID-19 disease presentation and severity', JCI insight, vol. 6, no. 19, e151777. https://doi.org/10.1172/jci.insight.151777

TY - JOUR

T1 - A dynamic mucin mRNA signature associates with COVID-19 disease presentation and severity

AU - Smet, Annemieke

AU - Breugelmans, Tom

AU - Michiels, Johan

AU - Lamote, Kevin

AU - Arras, Wout

AU - De Man, Joris G

AU - Heyndrickx, Leo

AU - Hauner, Anne

AU - Huizing, Manon

AU - Malhotra-Kumar, Surbhi

AU - Lammens, Martin

AU - Hotterbeekx, An

AU - Kumar-Singh, Samir

AU - Verstraeten, Aline

AU - Loeys, Bart

AU - Verhoeven, Veronique

AU - Jacobs, Rita

AU - Dams, Karolien

AU - Coenen, Samuel

AU - Ariën, Kevin K

AU - Jorens, Philippe G

AU - De Winter, Benedicte Y

N1 - FTX; DOAJ; (CC BY 4.0)

PY - 2021

Y1 - 2021

N2 - BACKGROUNDSARS-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.METHODSUsing 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.RESULTSWe 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.CONCLUSIONThis 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.FUNDINGThe Antwerp University Research and the Research Foundation Flanders COVID-19 funds.

AB - BACKGROUNDSARS-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.METHODSUsing 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.RESULTSWe 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.CONCLUSIONThis 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.FUNDINGThe Antwerp University Research and the Research Foundation Flanders COVID-19 funds.

U2 - 10.1172/jci.insight.151777

DO - 10.1172/jci.insight.151777

M3 - A1: Web of Science-article

C2 - 34448730

SN - 2379-3708

VL - 6

JO - JCI insight

JF - JCI insight

IS - 19

M1 - e151777

ER -

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

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