In our study, LASSO regression modeling determined a dynamic blood mucin mRNA signature that clearly distinguished patients with symptomatic COVID-19 from symptomatic non–COVID-19 patients based on expression of MUC1, MUC2, MUC4, MUC6, MUC13, MUC16, and MUC20 and distinguished between mild and critically ill COVID-19 patients based on expression of MUC16, MUC20, and MUC21 with high sensitivity and specificity for both models. Here, MUC13 is linked to COVID-19.