Here, we identified a mucin mRNA signature associated with COVID-19 presentation and severity along with the ability of baricitinib (JAK inhibitor), tocilizumab (IL-6R inhibitor), favipiravir (RNA-dependent RNA polymerase [RdRp] inhibitor), and remdesivir (nucleoside triphosphate analogue inhibiting [RdRp]) to suppress mucin hypersecretion and more specifically the mucins defining this dynamic signature. Here, IL6R is linked to COVID-19.