Coronavirus Replication

The genetic code for the SARS-COV-2 virus is RNA rather than DNA. RNA can make copies of itself just like DNA, so the coronavirus can make copies of its RNA genetic code using the machinery of the cell that it infects. In fact, when the spike protein of the virus attaches to the ACE2 receptor on the surface of the cell, it injects only the viral RNA into the cell. The viral RNA then begins to use the cell machinery to make thousands of copies of itself. At the same time, the new viral RNA starts to make the proteins that form the capsule and the spike proteins. These assemble themselves into new complete virus particles that can go on to infect other cells.

The “alphabet” that makes up the viral RNA molecule has only 4 different “letters” (called nucleotides). These are adenine (A), guanine (G), cytosine (C) and uracil (U). These nucleotides are combined in different sequences in the viral RNA. SARS-COV-2 has about 30,000 nucleotides. Different segments of these 30,000 letters code for all the virus proteins, including the spike protein that allows the virus to attach to the ACE2 receptors on the surface of human cells.

Mutations

SARS-COV-2 RNA makes some enzymes that ensure that the RNA is copied exactly. The letters for the RNA copies are in exactly the same sequence as the original RNA. This “safety check” is not perfect, but it’s pretty close. It probably works 99.99% of the time. Every now and then though the copying process accidentally substitutes one letter for another, say a G instead of an A. This is a completely random process. The virus does not “try” to make these mistakes (in fact it does not “try” to do anything). Even though these mistakes happen only .01% of the time, .01% of billions of virus particles ends up being a lot! The vast majority of these mistakes (mutations) either have no effect on the code for the proteins, or they adversely affect the proteins that the RNA makes and makes the virus less able (or unable) to infect other cells. Once in a blue moon, however, the mistake changes the spike protein in such a way that it attaches more efficiently to the ACE2 receptor on the cell surface. That means that this particular version of the virus becomes more infectious. Since it is easier for this new version to infect cells, it quickly proliferates and eventually replaces the original version of the virus. It then becomes what is called a variant.

When the virus is infecting lots of people there are more opportunities for variants to occur. In fact, the virus that started the epidemic in New York City was a variant that came from Europe and was much more contagious than the original version of the virus that originated in Wuhan, China.

We only find variants when we look for them. Some countries do a much better job of doing genetic sequencing on a significant percentage of positive coronavirus tests. The UK, for example does genetic sequencing on 10% of their positive tests. The U.S has taken a hit or miss approach, but it looks like we are soon going to get our act together and set up a system similar to that of the UK.

Current Variants

There is no commonly agreed upon convention for naming SARS-COV-2 variants. They are often identified by where they were first discovered. This is not a great way to name variants (witness the attacks on people of Asian descent caused by the term “China Virus”). I will use a naming convention that is most commonly used that names variants in relation to others.

D614G This was the first major variant identified in March of 2020. It was more transmissible than the original virus sequenced in Wuhan, China. It was the major variant in Europe and also caused the original epidemic in New York City. The current vaccines approved in the US work well against this variant. Monoclonal antibodies, which prevent serious disease if given within 10 days of getting COVID-19, also work well against this variant.

B.1.1.7 This variant was first identified in the UK. It is also more infectious and more transmissible. It has been identified in the US and is rapidly replacing the D614G variant. Vaccines and monoclonal antibodies also work against this variant,.

Cal.20C This is a more transmissible variant that has been identified in California. It has only recently been identified and it is not clear yet whether vaccines or monoclonal antibodies work as well against this variant

B.1.351 This variant first appeared in South Africa. It is the most worrisome, because it shows some resistance to currently available vaccines, and monoclonal antibodies don’t seem to work at all. It has been identified in the US.

P.1 This variant is circulating in Brazil. Not as much is known about it, but it seems to have the same mutation as the B.1.351 South African strain. It is apparently causing re-infection in people who had COVID-19 previously and recovered.

HOW MUCH SHOULD WE WORRY ABOUT VARIANTS?

The major concern about these variants is that they are more contagious and spread faster than the original form of the virus. The B.1.351 and P.1 strains are of particular concern because the monoclonal antibodies that worked so well for people at risk with early COVID-19 do not seem to work at all with these two variants. That means that people who get infected with these variants are more likely to get seriously ill and more likely to die.

The vaccines currently approved for use in the U.S. seem to work slightly less well at preventing infection from these two variants, but they still protect nearly 100% in preventing hospitalization and death. Vaccine companies are working on a booster shot that will work better against the resistant variants. Such a booster can be developed rapidly and does not have to be tested in thousands of people like the original vaccines. Such booster shots could be available in a few months. The problem is that currently only 9% of the U.S. population has received two doses of vaccine and only about 2% have had COVID-19 and recovered. Even that 2% may still be at risk of reinfection with B.1.351 and P.1.That means that 91% of Americans are still susceptible to infection with these variants, which are likely to spread rapidly.

We can prevent another surge of hospitalizations and deaths if we continue masking and social distancing for a few more months at which time we should be close to herd immunity from vaccinations. The actions of Texas and Mississippi in eliminating all restrictions are very worrisome (and very unwise). A surge in these states will not be limited to residents of those states. People travel and people congregate. Texas and Mississippi are essentially putting the whole country at risk of another surge. More people will be hospitalized and more people will die. I expect we will start to see an increase in cases in these two states in about 3-4 weeks. Hospitalizations will start to increase in about 6 weeks and deaths in about 2-3 months. I would love to be proved wrong, but we have played this tune before several times, and we know the outcome.

Bottom Line

The new variants are more transmissible and harder to treat. The three vaccines approved for use in the U.S. do not prevent infection quite as well with the new variants, but are still very effective at preventing hospitalization and death. Developing booster shots that work better against the new variants will be a fairly rapid process. In the meantime, until you can be vaccinated, masking and social distancing are essential to prevent another surge in cases, hospitalizations and deaths. Texas and Mississippi are putting the whole country at risk. If you live in those states please continue to wear masks in public, maintain social distance, and avoid closed indoor spaces until you can be vaccinated. Any of the three vaccines will keep you out of the hospital and keep you from dying of COVID-19.