Many Covid-19 cases are asymptomatic - but how does this happen?

• Data shows a large number of people infected with SARS-CoV-2 don't experience any symptoms.
• However, these individuals are still capable of passing on the virus, so understanding how this happens is important.
• According to a new study, the answer may lie in the virus' ability to prevent its genome from being recognised.

People who become infected with Covid-19, the disease caused by the SARS-CoV-2 virus, experience mild to severe illness, or even death – and then there are those who have no symptoms at all.

A recent study, published in PLOS Medicine, estimated that 20% of SARS-CoV-2 infections are asymptomatic (displaying no symptoms) but still contagious, begging the question, how does this happen?

According to new research by Aarhus University and Aarhus University Hospital in Denmark, the virus has the ability to prevent its genome (its genetic material) from being recognised.

The findings were published in EMBO Reports.

Immune cells and SARS-CoV-2

To gain an in-depth understanding of the phenomenon, the researchers looked at specialised immune cells, called alveolar macrophages (AMs), found in our lungs. They form an important defence against pathogens in the lungs.

According to a research article published in the American Journal of Respiratory and Critical Care Medicine, AMs clear out the air spaces of infectious particles that have evaded the mechanical defences of the respiratory tract, such as the nasal passages.

Since the lungs contain a significant number of these immune cells, they are likely the first cell type an invading virus encounters, the researchers explained.

Digging deeper, the team then looked at interferons – a group of cytokines that are essential in fighting viruses. When our body recognises a viral infection, our immune system initiates the production of these interferons.

Previous research has shown that AMs produce large amounts of interferons upon infection with respiratory viruses, such as influenza.

According to a news release by Aarhus University, new research also shows that interferon production in the infected epithelial cells can be inhibited by the new coronavirus, which typically infects the epithelial layer – the outermost cell layer of the lungs.

However, although the epithelial layer is the target of the virus, the researchers suggest it must be assumed that the first cell type the virus encounters are the AMs. These cells, therefore, play an important role in how quickly an immune response to a SARS-CoV-2 infection can be initiated, they explain.

The process

Considering all of the above, the team set out to investigate how these cells react to SARS-CoV-2.

In order to do this, AMs obtained from bronchoalveolar lavages (BAL) – also known as lung lavage or lung washing – from donors diagnosed with non-infectious lung disorders were challenged with SARS-CoV-2.

Following this, they examined the activation of the immune system in these cells upon encountering the coronavirus.

New coronavirus can hide its genome from being recognised

Alveolar macrophages have the potential to produce large amounts of interferons during a viral infection, such as influenza, but the researchers saw no interferon production in the cells when the alveolar macrophages were exposed to the SARS-CoV-2 virus.

This, therefore, suggests that in some people, SARS-CoV-2 can prevent its genomic material from being recognised in the alveolar macrophages. As a result, it does not induce the production of interferons, the authors say.

This explains why there is no activation of the immune system in the early stages of a SARS-CoV-2 infection, which ultimately allows the virus to spread more widely in the community before symptoms occur in individuals, the researchers explained.

However, they added that more research was needed to understand how the virus can avoid being recognised by the immune system.

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