Disclaimer: I am not a physician or a virologist. I have a PhD in cell and molecular biology. I did research in medical schools and was part of a clinical trial in a biopharma company. I have grown several viruses, but none in the coronavirus family. I am not associated with any group making vaccines to SARS-CoV-2. I have performed most of the laboratory tests described in this blog to detect virus and antibodies. I have made monoclonal antibodies, but not for COVID.
Do SARS CoV-2 viruses have to enter your lungs before you get sick? Yes. This section uses one virus and one cell to illustrate viral entry. But how many viruses will make you sick? I will now use this virus and COVID for the disease.
How many SARS CoV-2 viruses do you have to breathe in before you are sick with COVID-19? I found this information on https://www.erinbromage.com/post/the-risks-know-them-avoid-them It has been proposed that one thousand (1,000) virus particles can give you COVID. Viruses can be from different people at different times. Some investigators think the more particles you take in, the worst your disease, but this has not been proven. However, someone with severe disease releases more virus and greatest amounts are released on days 3-5 of disease.
How many particles are in the air from breathing, talking and coughing/sneezing? Air from the nose and mouth is made of respiratory droplets. Droplets can be large or small. You can even see a big sneeze in the air. Most large droplets quickly fall to the ground (where the kids are), but small ones hang in the air. Normal breathing release twenty virus particles in the air each minute, so 50 minutes near him/her will infect you. Talking releases two hundred viruses a minute, so infecting you in five minutes. A cough or a sneeze can release up to 200,000,000 virus particles that can fill a room/restaurant.
How does this virus enter your cells? A virus particle enters a cell using a lock-and-key mechanism. The key on the outside of the virus is the Spike protein. The lock is the ACE-2 receptor. This receptor named Angiotensin-converting enzyme 2 is an enzyme attached to cells located in the lungs, heart, kidney, and intestines. ACE-2 lowers blood pressure. Once Spike is attached to ACE-2, the membrane door opens and allows the virus to enter the cell, and blood pressure control is lost.
What parts of the virus enter the cell? As the complete virus is entering, the outside membrane comes off, like taking off an overcoat. This releases the strand of RNA (in blue) that is its genetic material. This RNA form is called positive sense or +RNA for a virus. This is the same form of RNA you have called mRNA for messenger RNA.
How do your cells normally use mRNA? For example, how does a cell make insulin? Your DNA gene for insulin is in the nucleus (and stays there). An mRNA copy of the gene leaves the nucleus and the cell machinery translates the message into insulin. Multiple mRNAs can be used at the same time to make thousands of insulins.
What happens to the viral +RNA inside your lung cell? The virus has two goals: to make more copies of the +RNA and to make proteins from it, like spike. There is no thinking involved, these are automatic events based on the biology of the molecules present. Your lung cell will start making viral proteins from the +RNA, just as if it were one of your own mRNAs. The lung cell cannot tell that it is making something harmful. The virus has hijacked your cell. So as the viral proteins are being made, what is going on with the +RNA?
How does this virus make more copies of itself? Each virus has a tricky way to make copies of RNA. In the last post I said I was going to explain mechanisms of virus replication in cells, like going from RNA to DNA. However, that pathway is not necessary for SARS CoV-2 to replicate in human cells. I decided to switch to more information about this virus after Pfizer released their vaccine data. The Pfizer vaccine inoculates people with synthetic viral +RNA. In the next post the details will be given, but the RNA injected is used as mRNA just like in the lung infection.
This virus makes a –RNA copy. Why? Assume only one +RNA entered your lung cell. One of the tricky viral proteins made from the original +RNA is an enzyme that will start making –RNA strands using the +RNA as a template. The –RNA cannot be used as mRNA, however, yet another viral enzyme will go backwards to make LOTS of +RNA copies, using –RNA copies as templates. These new +RNA can be used as mRNA or to make new viruses. Parallel mechanisms are making all the parts for new virus particles—new +RNA and the parts like Spike.
How do the pieces of virus form actual virus? Viruses are unique because they can self-assemble very quickly. When the lung cell cytoplasm is filled with millions of the individual components listed above, in seconds they come together into new virus particles. Each new virus is a replica of the original virus.
How do the new viruses leave the cell? Once assembled, viruses leave the lung cell through the cell membrane. Within hours of infection, thousands of new viruses infect more lung cells. Many cells break apart and die. This is called lysis and it releases cell parts that can cause immune responses like fluid accumulation and inflammation in the lungs. Some cells stay alive, making more and more viruses. As virus spread to more cells, the response overwhelms the lungs.
Can the lungs recover from this viral infection? When human lungs are infected with just a few coronaviruses, the immune system can destroy them and the person can survive. As the viral load increases, the lungs can become inflamed which involves fluid and cell molecules called cytokines that can also cause more fluid and cellular responses or pneumonia can develop. You may have heard of cytokines like interferon and interleukin in cancer therapy. As the lungs fill with fluid, ventilation may be needed. The problem with the response is that the lungs are fragile and the pressure needed to increase oxygen into the lungs can result in damage to the cells. All of this time more lung cells are infected and falling apart. This is a deadly virus.
Diagram from free article: https://theconversation.com/what-is-the-ace2-receptor-how-is-it-connected-to-coronavirus-and-why-might-it-be-key-to-treating-covid-19-the-experts-explain-136928
The next post, in a few days I promise, will be about vaccines.