For instance, COVID-19 is infectious even during the presymptomatic phase. Also, physiological processes that are harmful in one phase of the disease may become helpful later. For example, the angiotensin converting enzyme 2 (ACE2) receptor, which allows the virus to enter the body, may also be key to the protection of the lungs in the later phases of the disease.
However, in reality, the physiological processes underlying these phases overlap. People with COVID-19 may or may not show features of earlier or later phases.
Phase 1: Cell invasion and viral replication in the nose
More commonly known for their role in controlling blood 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 were not present on the surface layer of cells in the nose and were, therefore, not an important site for SARS-CoV viral replication.
In SARS, there are hardly any upper respiratory tract symptoms, and viral units are rarely present outside the lungs. This fact initially took the focus away from continuing to look for ACE2 receptors 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 supply of a protease called TMPRSS2, which chemically splits off the top of the coronavirus spike to allow the SARS-CoV-2 RNA to enter into the nasal cells.
Once inside the cell, the virus’s genetic material directs the cell to manufacture millions of new copies of itself.
According to a paper that has not yet undergone peer review, the protease TMPRSS2 can act more easily to remove the top 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.
As a result, 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 very 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 shown the importance 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 tract during the first 5 days of symptoms. The levels of the virus in six out of the 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 tract swabs was dropping from day 1, suggesting that the peak preceded the onset of symptoms. This has clear implications for preventing the transmission of the virus.
In a preliminary report by Menni and colleagues, which has yet to go through peer review, loss of sense of smell occurred 6.6 times more commonly in people with other symptoms of COVID-19 who went on to have a positive COVID-19 PCR test (59%) than in those who had symptoms of COVID-19 but tested negative (18%).
The ACE2 receptors and the protease TMPRSS2 have also been found in the supporting structures for the sheet of nerve cells in the upper part of the nose, which transmit signals about smell to the brain.
This is the first research to provide a potential explanation for this important symptom of COVID-19. However, this study is also awaiting peer review.
According to Menni’s study, loss of smell was the most commonly reported upper respiratory tract symptom in those testing positive for COVID-19, affecting 59% of people. It was more common than 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 might expect to see from a respiratory virus are not that common in COVID-19. For instance, only 4% had a runny nose, and 5% had a sore throat.