SARS-CoV-2-infected primary human airway epithelia illustrate mucus hypersecretion.

To monitor first SARS-CoV-2 interactions with primary, fully differentiated, ciliated, and mucus-producing epithelial tissue models, infection with clinical isolates derived from patients with SARS-CoV-2 was performed and monitored after 2 days by using confocal microscopy (Fig 1 [right]). Mock-treated, uninfected (UI) cultures served as negative controls (left). Immunofluorescence analyses revealed a significant infection of the tissue model with SARS-CoV-2 (pink [right]) and significant destruction, as recently described by us and as observed by high fragmentation of nuclei (blue) in particular within mucous areas (orange [right]). Infection with SARS-CoV-2 of both ciliated (green [right]) and mucus-producing cells (orange [right]) was detected. These analyses, which were performed by using the MUC5AC antibody for goblet cell staining in SARS-CoV-2–infected and UI tissues, revealed that infected human airway tissues showed an exaceberated mucus hypersecretion and mucus plugs (orange [right]), whereas in UI tissues no such plugs were monitored (left). UI tissues illustrated goblet cell staining (orange [left]) and intact, multilayered epithelia (blue [left]). Mucus plug formation was described when critically ill COVID-19 patients with airway obstruction and respiratory failure were analyzed (reviewed in Khan et al), and mucus hypersecretion in combination with proinflammatory cytokine activation, which we recewntly illustrated in our model, and reduced mucociliary clearance shape a vicious circle resulting in airway tissue destruction. Of note, these clinical manifestations were not only reported in COVID-19 but also during other viral infections, colonization by pathogenic opportunistic bacteria, or asthma (reviewed in Khan et al).

Fig 1

SARS-CoV-2 causes exaceberated mucus hypersecretion and plug formation. Visualization of mock-treated, uninfected or SARS-CoV-2 infected human airway tissues were analyzed after 2 days by immunofluorescence analyses (nuclei [blue], ciliated cells [green], mucous-producing cells [orange], SARS-CoV-2 [pink]).