COVID-19: What happens within the body?

How does your body respond when the SARS-CoV-2 virus infects it? Which physiological processes help or hinder us in eliminating the virus, and which processes make certain that we have a mild sort of COVID-19, the condition that the virus causes? In this Special Feature, we investigate.

The more we find out about COVID-19, the more we must question our assumptions about it.

Early on in the COVID-19 pandemic, our details about the disease came from clinical case reports of COVID-19 and what we knew about influenza pandemics and the serious acute respiratory syndrome (SARS) caused by SARS-CoV.

SARS-CoV is a coronavirus that shares 82% of its genome with SARS-CoV-2. In 2003, it caused an international SARS epidemic.

It quickly became clear that COVID-19 was very different than seasonal influenza, with higher mortality and infectivity, but it took longer to understand that there were important dissimilarities and similarities with SARS.

For example, COVID-19 is infectious even through the presymptomatic phase. Also, physiological processes that are harmful in a single phase of the disease may become helpful later. For example, the angiotensin converting enzyme 2 (ACE2) receptor, which allows the virus to enter your body, can also be key to the protection of the lungs in the later phases of the disease.

This feature describes what we realize up to now about COVID-19. To explain different processes that occur in the body, we have split the disease into four separate phases that roughly match the different degrees of severity: mild, moderate, severe, and critical.

However, in reality, the physiological processes underlying these phases overlap. People with COVID-19 may or might not exactly show features of earlier or later phases.

Phase 1: Cell invasion and viral replication in the nose 

Both SARS-CoV-2 and SARS-CoV gain entry with a receptor called ACE2.

More commonly known because of their role in controlling blood circulation pressure and electrolytes, these receptors are also present in the lungs, back of the throat, gut, heart muscle, and kidneys.

In 2004, researchers from the University Medical Center Groningen in the Netherlands reported that ACE2 receptor cells weren't present on the top layer of cells in the nose and were, therefore, not an essential site for SARS-CoV viral replication.

In SARS, there are almost no upper respiratory tract symptoms, and viral units are rarely present beyond your lungs. This fact primarily took the focus from continuing to consider ACE2 receptors in the nose.

Recently, a global team of researchers has found the ACE2 receptors on goblet (secretory) cells in and on ciliated (hairy) cells in the nose.

More recently, scientists have found ACE2 receptors in the mouth and tongue, potentially indicating a hand-to-mouth route of transmission.

Researchers also found a plentiful way to obtain a protease called TMPRSS2, which chemically splits off the very best of the coronavirus spike to permit the SARS-CoV-2 RNA to enter the nasal cells.

Once in the cell, the virus’s genetic material directs the cell to manufacture an incredible number of new copies of itself.

According to a paper that has not yet undergone peer review, the protease TMPRSS2 can act easier to remove the very best section of the coronavirus spike because a genetic difference between SARS-CoV and SARS-CoV-2 means that there is now an easily broken section known as the furin-cleavage site.

Consequently, SARS-CoV-2 can bind 10 times more tightly to insert its RNA into the cell, starting to explain why COVID-19 spreads so rapidly.

A small but careful study of viral samples from nine people admitted to hospital following contact tracing - as part of a cluster of COVID-19 cases in Germany - has proven the value of replication in the nose for the early spread of the virus.

On average, there were 676,000 copies of the virus per swab from the upper respiratory system through the first 5 days of symptoms. The levels of the virus in six out of your nine participants were undetectable in the nose and throat by day 10. Samples were available from day 1 of symptoms.

In all but one of the nine individuals, the viral load in the upper respiratory system swabs was dropping from day 1, suggesting that the peak preceded the onset of symptoms. It has clear implications for protecting against the transmission of the virus.

In a preliminary report by Menni and colleagues, which includes yet to undergo peer review, lack of sense of smell occurred 6.6 times additionally in persons with other symptoms of COVID-19 who continued to possess a positive COVID-19 PCR test (59%) than in those that had symptoms of COVID-19 but tested negative (18%).

The ACE2 receptors and the protease TMPRSS2 have also been within the supporting structures for the sheet of nerve cells in the upper part of the nose, which transmit signals about smell to the mind.

This is the first research to provide a potential explanation for this important symptom of COVID-19. However, this study can be awaiting peer review.

According to Menni’s study, lack of smell was the most commonly reported upper respiratory system symptom in those testing positive for COVID-19, affecting 59% of individuals. It was more prevalent when compared to a persistent cough (58%) or a hoarse voice (32.3%).

Interestingly, data from the first description of 99 people who tested positive for COVID-19 in Wuhan, China, suggests that some symptoms you may be prepared to see from a respiratory virus aren't that common in COVID-19. For example, only 4% had a runny nose, and 5% had a sore throat.