COVID-19 can be divided into three clinical stages, and one can speculate that these stages correlate with where the infection resides. For the asymptomatic phase, the infection mostly resides in the nose, where it elicits a minimal innate immune response. For the mildly symptomatic phase, the infection is mostly in the pseudostratified epithelium of the larger airways and is accompanied by a more vigorous innate immune response. In the conducting airways, the epithelium can recover from the infection, because the keratin 5 basal cells are spared and they are the progenitor cells for the bronchial epithelium. There may be more severe disease in the bronchioles, where the club cells are likely infected. The devastating third phase is in the gas exchange units of the lung, where ACE2-expressing alveolar type II cells and perhaps type I cells are infected.
The first phase of the disease is in the nose. Here the virus likely infects ciliated and secretory cells, replicates, but apparently does not induce a vigorous innate immune response.
The second phase of COVID-19 takes place along the conducting airways, the bronchi and bronchioles. The virus infects ciliated cells as the disease progresses deeper into the lung. SARS-CoV-1 infects ciliated but not mucus cells in air-liquid interface cultures.
The third phase of the disease is the lethal phase, as the infection spreads into the gas exchange portion of the lung and infects alveolar type II cells.
