Prevalence and Mechanisms of Mucus Plugging in COVID-19 Lung Disease

Purpose: To investigate molecular mechanisms of SARS-CoV-2-induced mucin expression and synthesis and test candidate countermeasures. Methods: Bulk RNA-seq was performed on well-differentiated human bronchial epithelial (HBE) cell culture lysates with/without SARS-CoV-2 inoculation. Results: SARS-CoV-2-infected HBE cultures exhibited peak titers 3 days post inoculation, whereas induction of MUC5B/MUC5AC peaked 7-14 days post inoculation. Conclusions: SARS-CoV-2-infection to HBE culture causes mucus goblet cell metaplasia and increased expression of MUC5B-dominated mucin overproduction. HBE cells were maintained >4 weeks on air-liquid interface culture until they were well-differentiated. Then the cells were inoculated with SARS-CoV-2 (D614G strain) apically at MON=0.5 for two hours. Cell lysates for bulk RNA-seq were obtained at 1-, 3- 7- and 14-day post inoculation from mock- and virus-inoculated cultures.