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 (AUC ROC 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 (AUC ROC 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.
【저자키워드】 COVID-19, Molecular biology, Innate immunity, 【초록키워드】 Treatment, Baricitinib, Mortality, Tocilizumab, Innate immunity, SARS-COV-2 infection, severity, Remdesivir, Favipiravir, drug, Symptoms, MUC1, Clinical outcome, COVID-19 treatment, Critically ill, Symptomatic patients, ROC, Sensitivity and specificity, mRNA, symptomatic, management, Patient, Mild, epithelial cells, mucin, respiratory, mucins, university, disease, expression, COVID-19 symptoms, Critical, parameters, secondary infections, Blood, association, symptomatic COVID-19, Respiratory Support, COVID-19 patient, AUC, Organ failure, critical cases, critically ill COVID-19 patients, pulmonary epithelial cells, MUC4, Critical case, healthy control, mild cases, foundation, lung tissue, healthy controls, RT-PCR assays, component, overexpression, diagnosing, mRNA expression, MUC13, MUC16, MUC2, MUC20, MUC21, MUC6, difference, transcriptional, expression profile, ENhance, Course, analyzed, investigated, correlated, induce, suppress, Antwerp, mild case, patients with COVID-19, patients without COVID-19, symptomatic patient, with COVID-19, 【제목키워드】 severity, mRNA, disease, with COVID-19,