Recently, some news services have been quoting a few physicians who have posited that “COVID-19 is losing its strength.” Additionally, there is a lot of talk about how the virus is mutating. I thought it might be valuable to look into these statements a little bit deeper.
MUTATION
All living things mutate. That is the underlying principle of evolution. Mutations can be destructive as in cancer, or beneficial as in the acquisition of HIV resistance or lactose tolerance. Most mutations go unnoticed. So, what is a mutation and how does it occur?
To understand mutations, we need to have a little background from your biology or chemistry class (sorry). In the cell is RNA. This is the “genetic messenger” molecule and is like the blueprint that the cell uses to build proteins. Think of the RNA molecule as a string of beads. Imagine that you have a cord with a knot at one end. You have a bowl of beads; the beads come in 4 colors, Red, Blue, Green and Black. You randomly take one bead at a time and string it onto the cord. When the cord is full, you have a long string of beads, randomly organized. You have created a perfect model of the RNA molecule.
Now, we can start to “read” the string of beads. We do this by starting at the knot and then counting the beads by groups of three. Each group of three beads is a “word” that tells the cell what protein to add to a new protein. For example, let’s say that the first three beads are Black, Green, Black; that is the genetic instruction word to the cell to add the amino acid “Glutamic Acid” to the protein chain. Black, Red, Black would tell the cell to add the amino acid “Valine” instead. And so, on and on, reading each group of 3 beads (or in scientific parlance, the RNA “Codon”) until the full chain of the protein is completed. At the end of the sentence of RNA words is a special codon, such as Red, Black, Green which the cell reads as “STOP”.
WHAT IS A MUTATION?
Mutations happen when, during replication, a change occurs within the bead sequence in the DNA or the RNA. With respect to our topic here, RNA, mutations occur when one of the beads in the RNA string is replaced by a different bead. So, maybe when a new RNA molecule is made, a “typo” occurs in the string of beads. Maybe the first codon we looked at above, Black, Green Black, is changed to Black, Red, Black. Now, the amino acid in the protein will be changed from Glutamic Acid to Valine. These types of single bead changes are termed “point mutations” because they are singular replacement events.
WHAT CAN CAUSE MUTATIONS?
Mutations can be caused by many types of things. For example, UV light can cause a change, and that is why we are careful when we expose ourselves or our children to sunlight. Some other chemicals that we inhale can also cause mutations, things like cigarette smoke, smog and dangerous chemicals. Stress, viruses and pharmaceuticals can all catalyze mutations in RNA or DNA.
WHAT HAPPENS WHEN A MUTATION OCCURS?
For many, if not most mutations nothing happens. The change in the protein is so small that it goes unnoticed. Sometimes the change is significant and can cause disease, sometimes it can result in a benefit.
In the example above, we talked about a SINGLE point mutation in the RNA string that resulted in the change of ONE amino acid in a protein chain from Glutamic Acid to Valine. This specific change is a particularly historic example of a point mutation. Here is the rest of the story.
This specific mutation occurred in the RNA coding for one of the 4 protein chains that goes to form human Hemoglobin, the molecule that carries oxygen around in the body; and it occurred in one particular group of the world’s population.
The mutation resulted in a great benefit for that population as the new hemoglobin molecule was quite effective in preventing infection from the parasite that causes malaria. This, as you would expect, produced an evolutionary benefit to those people who had the mutation, as it gave them a greater chance of living longer, avoiding the ravages of malaria.
Unfortunately, this mutation also caused an associated problem. The change in the amino acid sequence in that protein resulted in a stiffening of the protein, and this resulted in a change to the shape of the red blood cell, making it stiffer and more brittle. We call the condition “sickle cell anemia”, because the red blood cells no longer have their round shape, but a sickle shape, and because they are brittle, they tend to break, reducing the amount of oxygen that can be shipped around the body, resulting in decreased available oxygen, or “anemia”.
A single, point mutation in the genetic material coding for just one of the 146 amino acids in one of the 4 protein chains that make up hemoglobin provided both a very significant benefit and very significant problem for those people. In Africa, the value of protection from malaria exceeded the problems associated with anemia. Today, with malaria less prevalent, sickle cell anemia is a more important problem in the African American population.
VIRUSES ARE NOT INTELLIGENT
Viruses have no “motivation”; they do not “try” to become more infectious or less infectious, more lethal or less lethal, more or less anything. We often fall into the trap of ascribing motivation to something when there is no motivation, anthropomorphism to non-sentient objects.
We know that mutations are occurring in COVID-19, but we don’t have good evidence that those mutations have had positive or negative effects. These mutations DO provide us with a “passport” of the virus. When small mutations occur, we can easily track from where the virus came. This is how we know that the viruses in New York came from Italy, not from China. Although the original location of the virus was Wuhan, it was transmitted to multiple countries. At some point there was a point mutation in the RNA. That new variant spread through Italy, and then came to the East Coast of the US. The mutation has allowed us to track and identify its “nationality”.
IS LETHALITY DECREASING?
Possibly, but not likely.
But, you say, “there are now increasing infections and decreasing deaths.”
This is true. However, why is still up for debate.
- It could be that the virus has mutated and is less lethal, although this is really quite unlikely.
- It could be that deaths lag behind hospitalizations and hospitalizations lag behind cases. This is likely and we will know more as we move into July. (increased testing is a minor element in detecting increasing infections. The infection percentages are also increasing; the testing is still restricted to a subset of the population, not to the general public; and the increases seen outpace the increase in testing.)
- It could be that physicians and hospitals have learned quite a lot over the past 3 months regarding patient care, infection protocols and treatments. This is VERY possible. We have moved away from a random application of things like hydroxy-chloroquine and zinc, to medically demonstrated agents like dexamethasone and high-volume oxygen. These protocols and agents will continue to evolve over the next couple of months, and we can be optimistic that death rates will continue to decrease. Dexamethasone may eventually be replaced with other anti-inflammatory steroids; we may find that dosing needs to be changed up or down, applied earlier or later, in conjunction with other agents, etc.
As I have repeatedly said, I hope that by the end of August we will see a significant decrease in lethality. Let me add to that the optimistic hope that we will also see a decrease in the hospital stay times, which are currently above 10 days on average.
The combination of decreased mortality and decreased hospital stays will free up hospital and ICU space, increase everyone’s sense of safety and readjust the risk equation that we all use every day to decide what we are willing to do or not do.