The pathogenesis finer details of COVID-19 are beyond the scope of this course, but it can be briefly summarized as follows. SARS-CoV-2 Virus is thought to enter the host's body through breathing in exhaled air containing mainly aerosol particles (ultrafine particles present in the air and remain suspended for several hours) containing the Virus, either droplets or fomites.

The inhaled Virus SARS-CoV-2 likely binds to epithelial cells in the nasal cavity and starts replicating. There is local propagation of the Virus but a limited innate immune response. At this stage, the Virus can be detected by nasal swabs. Although the viral burden may be low, these individuals are infectious.

Then the Virus propagates and migrates down the respiratory tract along the conducting airways, and a more robust innate immune response is triggered. Nasal swabs or sputum should yield the Virus (SARS-CoV-2) as well as early markers of the innate immune response. At this time, the disease COVID-19 is clinically manifest. Unfortunately, about 20% of the infected patients will develop pulmonary infiltrates, and some of these will develop very severe disease. Initial fatality rate estimates are around 2%, but this varies markedly with age and medical condition.

The Virus then reaches the "gas exchange units" and infects alveolar type II cells. SARS-CoV-2 preferentially infects type II cells compared to type I cells. SARS-CoV-2 propagates within type II cells, a large number of viral particles are released, and the cells undergo apoptosis and die. The pathological result of COVID-19 is diffuse alveolar damage with fibrin-rich hyaline membranes and a few multinucleated giant cells. The aberrant wound healing may lead to more severe scarring and fibrosis than other forms of ARDS. Elderly individuals are particularly at risk because of their diminished immune response and reduced ability to repair the damaged epithelium. The elderly also have reduced mucociliary clearance, which may allow the Virus to spread to the gas exchange units of the lung more readily.

The immune response of the infected host is impaired, leading to high concentrations of Virus and pro-inflammatory molecules.

Click on the button to view a summary diagram of this process.