The most obvious clinical manifestations of SARS-CoV-2 infection are reminiscent of the flu. We have to say that the clinical picture of COVID-19 is much more complex: the most of the infected people recover from the infection without complications, but about 20% of the patients experience severe pneumonia and respiratory failure.

It is important to consider the four stages of the pathogenetic process to understand how the same virus can cause such a variety of clinical responses.

The different phases

In the first phase of the pathogenetic process the virus penetrates in the upper respiratory tract and it uses the ACE2 receptor (enzyme) to infect the cells of the nasal mucosa. During this stage the person is contagious but can be asymptomatic.

During the second phase the virus spreads in the respiratory tree descending along the airways, causing the first symptoms; in this phase the signals of the innate immune response often become evident.

In about 20% of patients the disease evolves towards the third stage, which is characterized by pneumonia and breathing difficulties. In fact, during this phase the virus reaches the pulmonary alveoli which is the site where the exchanges of respiratory gases between blood and air take place. The virus triggers an inflammatory response that leads to the release of inflammatory cytokines (mediating proteins) and invokes immune cells by infecting the cells that line the alveoli. This reaction can damage the epithelium that lines the alveoli favoring the entry of fluid from the capillaries that surround them and preventing respiratory exchanges: at this point breathing difficulties begin to appear.

During the fourth phase, the patient may develop the so-called “cytokine storm”, which is a syndrome characterized by the hyper-activation of immune responses and the uncontrolled release of inflammatory cytokines: the effects affect the whole organism, causing serious or even fatal damage to the organs.

There’s why some people are more vulnerable to the effects of the coronavirus

Elderly people with chronic or immunocompromised diseases are the most at risk. But in the case of coronavirus infection, environmental and behavioral or genetic factors could also come into play. Indeed the gene encoding the ACE-2 receptor is located on the X chromosome. Heterozygous women could be more protected when a particular polymorphism is responsible for an increased vulnerability to infection, because they have two copies of the gene, rather than just one as occurs in males.

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