The Immunology of SARS-CoV-2 (COVID-19)

First, some clarifications on nomenclature. The virus is named: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease this virus causes is coronavirus disease (COVID-19). It’s just like HIV is a virus that causes AIDS, and you can have the HIV virus without having AIDS, much like you can catch the coronavirus and be infectious without having symptoms ie, coronavirus disease.

So what makes this virus different from influenza? The answer boils down to how the virus gets into the cell. Viruses have something called a spike protein that has to bind to a receptor on the target cell to initiate viral entry into the cell. Influenza interacts with sialic acid to enter the cell, whereas SARS-CoV-2 binds with ACE2 receptors.

ACE2 receptors can be found abundantly in the epithelial cells of the lungs and the small intestine, but also the blood vessels, kidneys, and testes. This explains why that while most people with COVD-19 have respiratory issues, you may also develop symptoms like diarrhea and you can actively shed the virus through your stool.

Because these viruses bind to different receptors, the drugs that have been developed to block influenza cell entry will not work for SARS-CoV-2. Other classes of antiviral medications like the anti-retroviral drugs designed to combat HIV work on mechanisms that coronavirus doesn’t use. This is why there are currently no treatments for corona virus besides palliative care.

In addition, SARS-CoV-2 has the ability to undergo something called furin cleavage. Furin is a protein that functions as an enzyme, and is found in the majority of cells in the human body. SARS-CoV-2 uses the ACE2 receptor to get to the cell, and then furin cleaves the viral envelope to allow the viral components into the cell. 

SARS the first did not have furin cleavage, and so it was much more difficult for SARS to infect cells. This means that SARS-CoV-2 is more infectious than the original SARS. This also means that SARS-CoV-2 may present with atypical symptoms because it can impact most cells in the body.

Once SARS-CoV-2 is in the cell, it activates what we call the inflammasome. This is the collective name for complexes within a cell that initiate the inflammatory part of the innate immune system. They are plentiful within epithelial cells, which makes sense as these cells are often the first to come into contact with pathogens. 

SARS-CoV-2 interacts in particular with the inflammasome complex type NLRP3. This is what drives a lot of the symptoms of COVID-19, like fever, and if unchecked by the body, may develop into what is called cytokine storm. There are no drugs and herbs that put the body into cytokine storm, it is a process that is driven directly by the virus. There is research on herbs like elderberry showing that it increases cytokines, but it is within a normal and appropriate parameter and does not drive the body into cytokine storm.

The good news is that we already had research on NLRP3 before COVID-19 emerged. We know that vitamin C can help and so can rosmarinic acid. Rosmarinic acid can be found in the lamiaceae family, which includes herbs lemon balm, rosemary, thyme, oregano, lavender, peppermint and spearmint.

Melatonin levels tend to be higher in those who have less NLRP3 activation, but it is hard to say whether this is merely correlation or if it is causative. Children have higher levels of melatonin than adults do, which correlates with children being less affected by SARS-CoV-2. However, children also have lower levels of overall inflammation, and so this may be the more causative reason they are less likely to have symptoms from SARS-CoV-2.

The other action item here is working to decrease interleukin 6 (Il-6). Il-6 is associated with anxiety type behaviors, and so it is no surprise that many of the herbs that decrease this cytokine are traditionally used for calming the nerves. Lemon balm, passion flower, and ashwagandha all help decrease Il-6. Feverfew does as well, and this NLRP3 may be the mechanism by which it lowers fever.

Now that you understand the mechanisms by which SARS-CoV-2 impacts the body, it should be clear that it is a big deal insofar as we have no medical treatments for it, it is more infectious than other coronaviruses, and it has several mechanisms of virulence.