"Mutations are Normal, Many Of Them Die Too": Dr Jeremy Kamil

To understand COVID-19 mutants and explain how they work we spoke with Dr Jeremy Kamil, Associate Professor of Microbiology and Immunology at the Louisiana State University Health Sciences Center at Shreveport.

The number of COVID-19 cases continue to rise dramatically across India with close to 54,000 fresh cases as of March 30.

Some states have been worse hit as have been cities like Mumbai where cases almost hit 7,000, a record since the start of the pandemic.

A question increasingly being asked is if and whether new mutants of the coronavirus are driving this rise?

And if so, where are they coming from, how do they get created and how will they behave, and most importantly, are they more lethal than their `parentage'?

To understand COVID-19 mutants and explain how they work, BOOM's Govindraj Ethiraj spoke with Dr Jeremy Kamil, Associate Professor of Microbiology and Immunology at the Louisiana State University Health Sciences Center at Shreveport. Dr Kamil is also a Director of the COVID-19 viral sequencing project and holds post doctoral fellowships from Harvard and Cornell Medical Schools.

Full transcript of the interview follows

Govindraj Ethiraj: Let me start off with a very simple question so that we can lay the foundations. What is a mutation and what do we understand of the term mutation in the context of a virus like COVID-19?

Dr Jeremy Kamil: The simple thing is that everyone should be reassured that mutations are normal, they happen every time the virus replicates and most of those mutations are meaningless from a danger standpoint.

The things get interesting and newsworthy perhaps when you talk about things called 'variants of concern' or 'variants under investigation'. And this refers specifically almost always to mutations in what is called the spike protein of the virus, the gene that encodes the spike protein to be more specific.

So, I would say most viewers should not be too alarmed when they hear about a new variant in the newspaper. It just reminds us that the pandemic is not yet over, the virus is, always, every once in a while, a mutation will happen and it is like the virus won the lottery…….I told you that most of those mutations are meaningless.

But every once in a while the virus will explore sequence space, by chance it will find a mutation that will help it get into the human cells a little bit better or to escape an antibody that was made against an early wave pandemic infection. But keep in mind that the virus is not a super virus, it has no magical abilities compared to the other viruses that can make us sick. So this is all normal stuff that we should expect to see. The important thing is to keep in mind to wear masks, to socially distance whenever possible from people outside your household, and to get a vaccine as soon as you're able. Those are the same messages that were sent in the beginning of the pandemic.

Govindraj Ethiraj: So any virus will and can mutate--a flu virus for instance, will also do the same thing..?

Dr Jeremy Kamil: Yes, everytime. Everytime they replicate they make mutations. It is just like a typo, like when someone asks you to copy a book by hand, very, very quickly, you may misspell a letter or two. No matter how good you are at copying. And the virus is no different; it has to copy its genome and it does it only somewhat faithfully. It makes little mistakes every time it copies. Some of those mistakes kill the virus.

A lot of the mutations are lethal to the virus and you do not see those because they die. So the ones you see are either neutral, they ride the coattails of the rest of the virus' genome or mutations that are a little bit more fit. And these are small differences.

The virus isn't evolving magically to drill a hole in your mask or to do things it could not do before really. So there is nothing to be so alarmed about except do have some awareness that there are variants like B117 (B.1.1.7) that was first described in the United Kingdom, and of course it has made its way to India, and lots of part of the world and in some countries it is the major virus around.

Because it has some significant advantage over the parental virus in spreading from person-to-person. But again it is not such a big deal.

GE: And you said that in the case of some mutations that causes the virus to die, so is that also happening with COVID-19. Would that be a safe assumption?

JK: Happens every time the virus replicates. There are defective viruses that are unable to infect another person or complete the replication cycle. But those are not selected for, they are selected against. So you do not see them so much; in the sequencing you do not detect those.

GE: Now tell us about how viruses or their mutations behave when it comes to geography. So why is it that some mutations seem to gather more steam in some countries or geographies or maybe it is some other factor that you could tell us about..

JK: I think that the most important factor that influences all this is something called undersampling or disparate sampling. And that is a scientific work/word for some places are doing a better job sequencing and sharing their data in real time than others. So it is a really important initiative, GISAID (a global initiative to promote rapid sharing of data from all influenza viruses and coronavirus in an open access format) and is for sharing pathogen sequence data in real time. And they really protect the rights of the authors and the scientists in countries like Bangladesh, Brazil, India, South Africa but even in states like Louisiana.

I work in a state in the United States that is not as wealthy as Masscheuttes or California. And if it wasn't for GISAID, me sharing that data in real time...I wouldn't have had all the news coverage and the scientific paper that came from collaboration with other scientists who saw my data on GISAID. But they knew when they saw my data that they were bound by the same data user agreement that I am, which says, I cannot release sequences or use someone else's data, they trusted the community, they shared it real time, they shared it under an agreement.

So that means that when you share in real time you get rewarded because no one can share your data without attributing it to you and you are encouraged very strongly to collaborate with others and share. So the problem is we are hearing all news reports that this virus came from England, or this one emerged, this double mutant from India but there are viruses coming in from everywhere.

Some places are either not sequencing, not sampling, or are not releasing their data in real time. So if you sit on your data for 2-3 months, your data is less valuable. It is not news anymore. Who wants to read the newspaper from three months ago, when you could read today's. And you need to release the data as soon as possible to understand the virus.

GE: You are saying from your experience and concluding that because we see data only from some places, it does not mean that there are no mutants or mutations swirling in other places and it is only because we do not have the data we do not know?

JK: Exactly right. It is like turning a light on. If 90% of the world is dark and you are looking at only 10%, you see a scary insect or something you will say Oh My Gosh..where the light is, it is a scary insect. But there is a whole universe of insects in the dark that you are not seeing, because you do not sequence there, or share that , or maybe people are hiding in the dark holding on to their little treasure, the special little thing that they think is so cool.

So they want to look at your data but do not want to share theirs. You know who loses from that? The person who thinks they are better off holding their data. And public health, people do not find out about a new variant. Let us say, there is a new scary virus, it got sequenced, but someone who understands what that means maybe they are in Brazil, maybe they are indifferent country that might collaborate with and help you understand that all the mutation on your spike is similar to the one we saw in our village and let us talk, let us collaborate, and you can have a paper in Nature, or Science….itself. But if you sit on your data you lose that. And someone else finds it later.

GE: I am guessing that you are also saying that there are countries or geographies that are not sharing clearly as much data as they could because sharing the data may actually create a sense of..

JK: Ya, no exactly. Sharing in real time makes the pie/pipe bigger. Often in science, and I do not blame scientists, we are all used to this economy or the ecosystem of competition. So we all think, if I share this right away, someone else may take it because I am competing for the same grants with them, I am trying to get into the same journals that they are.

But with this rapid data sharing, it is really a situation where you can make the pie/pipe bigger. You can have more to share because the public understands more than ever before, that the viruses are around, we need to know how they look like and how they are evolving to protect human health and also to inform when your child goes to school and come home with a fever, often times you do not know what virus that was. But we are now knowing, world leaders in India, Europe, in South Africa, in Brazil...everyone agrees now.

The US, the rich and the lower middle income countries…..quote unquote, poor countries, developing countries everyone is going to call them, everyone is going to be sequencing like utility. Sequencing should not be research, it should be a utility like the weather. Like you should know when you wake up in the morning, you should be able to see a number that says here is Infection Risk Score and I can tap that number and see that, Oh the risk of this respiratory virus is Number 4 and the way to protect against it is to wear a mask.

And if some child goes to school and find out that their cousin had a fever and they sequenced it and they can look on their computer, and say oh this is the virus that made my cousin sick; and we all share it under some kind of cooperative agreement so that no one is having their data taken from them and publish about.

If you sequence in India, and you find a cold virus, and someone in London should not publish it without involving you as an author.So that is what GISAID is all about. This real time data sharing is about equity and being fair and honouring everyone's contribution.

GE: And that is critical to understanding the spread of the disease...So in India, we peaked towards the end of September 2020 and it was on a steady and downward trend and suddenly last month, it started picking up. In the month of February it started picking up and now as we enter April it is skyrocketing once again. Do mutants play a role in this and if not, what could from your understanding drive this sudden spurt, apart from the obvious changes in behaviour which is people taking it easy….

JK: People's behavior is the number one driver. The other is you do have variants now that do two things. One they are inherently able to spread faster, the archetype or prototype …… of that, the best example of that is B117. It definitely spreads faster and is actually a little more dangerous. However, B117 can be easily controlled by all the current vaccines. The other category that might be leading to a surge are viruses that have mutations in the spike, that allow them to escape or resist antibodies that were elucidated or came when people recovered from a case of COVID-19 early in the pandemic.

These viruses like B1351 and another one called P1, they can infect people who already have antibodies. They do not make people who already have antibodies very sick, but I would call the….herd immunity. Because now this virus can hop between people who already can resist B117 and all the earlier viruses until they find someone who has never gotten infected. And that person has the risk of getting pneumonia, or getting into the hospital or dying. So, that could also play a role in the surge of these infections.

And we know we see all over the world now. Just like this double mutant that was identified in India, it has a mutation called E484Q, and the 484 position on the spike is known when it changes to a K..that escapes the antibodies quite well and it is also know that when it changes to a Q-- in laboratory experiments-- that escapes antibodies quite well. It does not mean it escapes all antibodies, so if someone gets infected with a virus that already has a Q or K there, their antibodies will protect them again from being infected.

But if they were infected by the parent virus, or older virus, that mutation can help the virus maybe infect a few cells in their mouth and the nose. They will again not be likely to be very sick, but they could transmit the virus from person to person. So the second wave, I would say, is probably contributed by variants of two types. Ones that transmit more rapidly like B117 and ones that escape antibody responses. And the double mutant that was found in India, has also been seen in a lot of other countries by now.

And that will have some advantage in escaping from antibodies. Maybe it spreads a little faster too. I think WHO has a list now they may …..and some people think that P1, and B1 and E….not only escape antibodies but also spread a little faster. So yes, variants are probably contributing.

GE: In your understanding and studies are there any external factors that contribute to it for instance, you know, last year in summer, like it is right now in India, we thought that maybe as temperatures rise the virus would not transmit at the same intensity. Though clearly that seems not to be the case, as it is summer once again here and the virus seems to be spreading. So, are there any external factors in your mind that work to spread the distribution or curtail it?

JK: I think the seasonality of corona virus probably in large parts is driven by what we generally call human behaviour. Because in the United States...look this virus likes to spread indoors, in crowded areas that do not have great ventilation. So anytime that people like to get together in restaurants, or religious holidays or cultural events, people are gathering together indoors and are doing the things that they love to do.

We like to socialise, we like to see our families. And India is a populous country with people who have big families and big communities and any time of the year whether it is summer or winter people are gathering together indoors, or crowding on a bus with the windows closed that is going to be a perfect environment for the virus to spread.

And the variants like B117 that will probably spread even faster and need less of the confinement, less ventilation than maybe the older strain….but still they are all going to benefit a lot from people gathering together indoors. If you are gathering together indoors with people who you do not live with , I recommend that you wear a mask. And you ask others to wear one as well.

That just protects everyone until we get vaccines.Once we have everyone vaccinated , the case numbers go down, we can relax the masking. No one likes wearing a mask all day, it is not fun. But we like it even worse when someone who we like is very ill. So I think do what is best for your family and friend.

GE: Dr Kamil as we look ahead now, we are maybe depending on which country we are, maybe somewhere one third of the way to vaccination, or atleast being in a better position to control the medical outcomes of people falling ill and even going into, say, the ICU. So what are you looking at and how are things looking to you at this stage of either vaccination and the spread of the disease?

JK: The thing that worries me the most is not the situation in Europe, or especially the United States. The US can be greedy about protecting itself. We are doing a great job vaccinating our people. What I worry about most is about countries that have no access to vaccines. We are all in this together, the virus is a pandemic, a worldwide virus and we need to make sure that everyone all around the world has access to the best of vaccines.

This is not the time when one country should be trying to be ahead of the others. We should all be trying to protect humanity here because we depend on each other. So what I worry about the most is that the pandemic is going to go longer than it needs to because people can't come around a table and agree to share and solve the problem together. Because we need to make sure that the vaccines are available in Africa, Bangladesh, in India, in Russia, all over.

And what scares me is that the vaccine rollout is much slower in some countries than others. Brazil is really in a bad situation right now from everything I hear. And I vaccine will stop the pandemic, we already see that. The case numbers are coming down. There are little spikes in the US but every indication I have is that the vaccine will control the pandemic. They will not eliminate the virus. They will eliminate the disease.

Updated On: 2021-03-31T21:46:15+05:30
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