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Ask an Infectious Disease Expert: What Do We Know About COVID-19 Mutations?

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Makeda Robinson, MD, PhD, is an infectious disease specialist currently studying virus-host interactions in emerging viruses at Stanford University. Each week, Dr. Robinson breaks down complicated COVID-19 topics and addresses pressing public health concerns.

As scientific efforts to wipe out SARS-CoV-2 intensify, so do the structure and activities of the virus. We are doing everything we can to keep SARS-CoV-2 off the map, so it is doing everything in its power to stay on it. Primarily: it is mutating.

What do these mutations mean? Will they prove more harmful to us than the original virus, or are they benign occurrences? Most importantly, how will these mutations affect our current treatment and vaccine efforts? Dr. Robinson spoke with Verywell Health about the science behind viral mutations and what they mean for the future of SARS-CoV-2, as well as efforts to identify and eradicate it.

Verywell Health: Why does a virus mutate? 

Dr. Robinson: Viruses, like humans, are under constant evolutionary pressure, so the goal of a virus is to survive and multiply. The mutations that occur in a virus are often a response to the different efforts of our immune system to identify and neutralize it. Each time a virus replicates, random mutations are made in its genome. This occurs more frequently in RNA viruses like SARS-CoV-2 compared to DNA viruses like herpes viruses, which we’ve been living with for longer.

Viruses like SARS-CoV-2 and the original SARS virus jumped into humans from other animal hosts. When they first infected humans, it was like a whole new world for them. They had to learn how to adapt and change in an environment that is trying to search out and kill them, triggering a “survival of the fittest” scenario. Each virus will have its own abilities to navigate the human immune system, and the strains with the best evasion tactics will become dominant. 

If the mutation leads to an infection that is rapidly lethal, it will do too much harm to the host, losing the opportunity to infect others in the community. In this way, the virus can quickly go extinct and is unlikely to cause a global pandemic.

On the other hand, if the virus is too weak, our immune systems will rapidly detect and kill it, preventing the virus from replicating and spreading to others as well.

There is a sweet spot for a virus where it can infect and spread as efficiently as possible. The longer amount of time it has to evolve with us, the better it becomes at adapting to our defenses.  

Verywell Health: Are virus mutations always a bad thing?

Dr. Robinson: Virus mutations don't necessarily have to be a bad thing; they’re a natural process that occurs during the viral lifecycle. In fact, many of the mutations are completely benign changes. Viruses go through the process of natural selection, where the viral strains best equipped to thrive in a new environment will win out. Tracking these changes, in a way, is like putting together a family tree and understanding how each branch is different, but related to the other. 

However, as a virus begins to drift from its original sequence, we do have to be more cautious about the prevention methods and treatments that we’re providing. If those interventions are directed at the virus itself, they may not all work as uniformly as they would have earlier on. As the virus becomes more deeply acquainted with its host, its defenses change accordingly. So we will have to be even more thoughtful about how we design therapies than we may have had to be earlier on when the virus was more homogenous. A treatment that may have worked well in April may not have the same effect in October, because the virus has evolved.

Verywell Health: Have there been any mutations in SARS-CoV-2?

Dr. Robinson: The virus has developed several mutations that are circulating in the population right now. A recent study that sequenced over 7,000 genomes identified 198 different recurrent mutations.

While many of the mutations are harmless, researchers did find a specific mutation in the spike protein—the part of the virus that latches on to human cells—which has now become the dominant global strain of the virus. This means that when we’re looking back at the original genome that was sequenced from Wuhan, China, that particular genome sequence is no longer the most common, and this new spike protein is now the dominant strain. The mutation has been named G614, meaning there was a change in the amino acid at the 614th position. 

Many of the vaccines being developed right now are targeting the spike protein, so if we’re seeing a true shift in the sequence of the target, we have to be incredibly cautious about what we label as a "sufficiently neutralizing response" in vaccine clinical trials.

I believe we also need to be thinking about combination therapy and continuing to develop other approaches in parallel. Identifying areas of the virus that are consistent between strains may provide our best chance at designing the best therapies and vaccines moving forward. If we are thinking about having only one specific target, then we need to ask ourselves if that approach will continue to work as the virus continues to adapt and change. 

Verywell Health: Have any of these mutations made the virus more lethal?

Dr. Robinson: We are still learning about the virulence factors associated with the emerging strains. Some of these mutations may lead to an increased rate of infection or reinfection.

The first reinfection case was recently described in Hong Kong. The patient was initially infected with a viral strain similar to the original Wuhan strain, and was then infected four and a half months later with a different viral strain. The strain of the reinfection contained the new spike protein mutation, which has been associated with more severe disease.

A recent Cell paper looked more closely at this specific mutation, referred to as G614, and found that those infected with a virus containing the G614 mutation had a longer duration of viral shedding. This means they were contagious for a longer period of time. Researchers also found that when infecting cells in the lab, the G614 virus demonstrated an up to a nine-fold increase in infectivity compared with the original spike protein sequence, called D614.

Verywell Health: If someone acquires SARS-CoV-2 immunity, is there a chance they won’t be immune to a mutated strain of the virus? 

Dr. Robinson: The reinfection case has brought up important questions about whether these new mutations may be affecting the way the virus triggers our B and T cells responses, which are the immune cells we need to fight off the virus and develop antibodies. Several of the mutations seen in the reinfection case have the ability to interact with the adaptive immune system. This raises concerns that the immune response that some people have developed to the initial SARS-CoV-2 virus in the spring may be different than the responses needed to mount an effective response to the SARS-CoV-2 virus that is currently circulating. This makes the development of an effective vaccine even more complex and vital. 

Verywell Health: Is this virus mutating at a normal pace compared to other viruses?

Dr. Robinson: SARS-CoV-2 seems to be accumulating about two mutations per month on average, a rate that is two to four times slower than influenza. The goal now is going to be learning how different strains respond to us and diving deeper into these variants. 

Verywell Health: One potential mutation identified by scientists has been linked to milder cases of COVID-19. Does this mean mutations can be good? 

Dr. Robinson: There has been a documented mutation which appears to in fact weaken the virus. Infection with a viral strain which contains a 29 nucleotide deletion may reduce the severity of the virus. It has been described as leading to a lower probability of patients requiring supplemental oxygen, and may also have lower rates of replication.

We are still learning why a weaker virus would not simply go extinct. Having a “weaker” version of a virus could have benefits and risks to us. The weaker virus may not make us super sick, but it increases the possibility of infecting more people. We also may not mount a strong enough immune response, preventing those who have been infected from creating sufficient antibodies.

Verywell Health: How do the mutations of SARS-CoV-2 affect vaccine developments? 

Dr. Robinson: This is an essential question when thinking about developing the best vaccine strategies. We are likely going to need a combination of approaches if the goal is to stop the spread of the virus. One vaccine targeting one specific viral antigen may not be enough.

We are also still learning about the safety and efficacy of the newer vaccine technologies which need to be vetted before being administered broadly. Finding ways to mount an immune response with the appropriate breadth and depth to overwhelm and neutralize the virus is going to be the key to developing adequate immunity to support herd immunity. We have to learn whether these new strains and mutations will weaken our response to vaccination. 

Verywell Health: What’s one important thing that people need to know regarding mutations? 

Dr. Robinson: We all need to keep living our lives like we are at risk for infection. Even if you’ve had a COVID-19 infection in the past, please continue to live your life as if you are at just as high a risk as anyone else. The emerging data about mutations and reinfections should make us wary about the idea of the immunity “certificates” or “passports,” where those who have been previously infected no longer need to adhere to the same guidelines as those who are still naive to the virus. We should all still be focused on using all the tools available to us to protect ourselves and our communities.

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