SARS-CoV-2 changes classic feature of virus becoming endemic: Shahid Jameel

SARS-CoV-2 changes classic feature of virus becoming endemic: Shahid Jameel

Shahid Jameel, former head of the Indian SARS-CoV-2 Genomics Consortium, speaks to DTE about how a virus mutates, the trajectory of COVID-19, concerns regarding re-infection

The novel coronavirus disease (COVID-19) pandemic is poised to enter its third year. The new Variant of Concern, Omicron, which has already spread in at least 70 countries in under a month, has sparked renewed fears across the globe.

With over 270 million cases and over 5.3 million deaths globally, no country has been spared. Vaccine efficacy too has come under question, with preliminary reports revealing a reduced neutralisation of the mutated virus.

What have we learned about the SARS-CoV-2 virus and its mutations till now?

Dr Shahid Jameel, eminent virologist and former head of the Indian SARS-CoV-2 Genomics Consortium (INSACOG), speaks to Down to Earth about how a virus mutates, the trajectory of COVID-19, concerns regarding re-infection in the backdrop of waning immunity and vaccine efficacy.

Taran Deol (TD): How does a virus traditionally behave?

Shahid Jameel (SJ): What happens when any genetic material multiplies? Our cell splits into two, the deoxyribonucleic acid (DNA) present in it also makes a copy of itself so that each cell gets the same information.

Viruses are the same. Whenever any genetic material is copied, it is copied by enzymes, whether it’s the genetic material of our cell or of a virus, and enzymes often make errors. Our cells have other enzymes that can detect this error and correct it. Viruses don’t have this proof-reading mechanism.

There’s also a difference between viruses that have DNA as their genetic material and those that have ribonucleic acid. The former depends on the enzymes that are present in our cells to multiply. Therefore, they can take advantage of the proofreading mechanisms.

When an RNA virus multiplies, it uses its own enzymes, and therefore can’t correct the errors.

Mutations happen at random because of errors in copying. These errors accumulate. And while these errors happen at random, what mutant virus gets selected depends on other factors. The only mutations we see are the ones that give some selective advantage to the virus.

TD: Is SARS-CoV-2 following this trajectory? When will it become endemic?

SJ: It’s not possible to predict when COVID-19 will become endemic. It depends on how much capacity this virus has to mutate and even that is very hard to predict.

I do think the virus is changing towards becoming more transmissible and less severe and that is a classic feature of viruses going from epidemic to endemic.

Omicron is more transmissible than Delta and as per initial data, it’s less severe also. It’s on its way to becoming endemic, but when that will happen cannot be predicted.

Whether another variant will emerge and replace Omicron on its way to becoming endemic is a possibility, but can’t be predicted.

TD: With COVID-19 entering its third year, it will become the longest-running pandemic since the 1918 Spanish flu outbreak. What have we understood about it so far?

SJ: I will make two comparisons. SARS-CoV-1 and SARS-CoV-2 are from the same family of viruses but have manifested very differently.

The key difference is that while SARS-CoV-1 was transmitted from one person to another when the person showed symptoms, SARS-CoV-2 spreads even before one starts to show symptoms.

This, to me, is the critical difference why SARS-CoV-2 has spread so much while SARS-CoV-1 did not, even though the latter was more lethal.

The 1918 Spanish Flu was caused by a virus with a genome size smaller than the COVID-19 virus. The flu virus has about 15,000 bases, while coronavirus has about 30,000, which means it has a greater capacity to mutate.

Just the mutational space on the virus tells us that coronavirus has much more capacity to change than a flu virus in normal times.

Coronavirus is likely to be in the flu category. We will need boosters frequently till this virus becomes so entrenched in the population that everyone has been exposed to it. And then if the virus changes a little bit, we’ll need either boosters every few years or it will infect us mildly.

COVID-19 will also become a cold-causing virus, but it’s not done yet. New variants will emerge, local spikes will continue to happen. As more and more people are vaccinated, the duration between those spikes will increase and the magnitude will reduce.

That’s how this virus will become endemic.

TD: The World Health Organization (WHO) has warned of re-infection risks with Omicron, this is coming in the backdrop of waning immunity.

SJ: When everyone is talking about immunity, they are actually talking about antibodies. But immunity is more than antibodies.

When our body responds to a foreign object like a virus, it raises two kinds of immunity. One is called antibody-based immunity, which protects from infection. The other is called T cell-based immunity, which kills infected cells and protects them from disease.

Following an infection or vaccination, the level of antibodies will go down with time. But a memory response is developed, which triggers the body to produce antibodies and T cells when infected with a virus it remembers.

It’s very easy to look at antibodies, it’s much more difficult to look at the T cell responses, and these responses come downstream anyway. By saying that immunity wanes, what people mean is that with time, more and more of us will get a symptomatic infection. But it doesn’t mean that more of us will get the disease.

If the goal is to protect people from severe disease and not re-infection, that’s very doable. What is acceptable in each country or region would depend upon its healthcare system.

TD: What about booster doses? It raises not just clinical, but also ethical questions.

SJ: Giving boosters at this time in a country like India is really putting the cart before the horse. India has fully vaccinated only about 38 per cent of its population.

So, saying that you should allow boosters means that you’re taking those doses away from people who have had only one dose or none.

Our priority should be to get the second dose to people who already have one dose and two doses to people who have none. But that doesn’t mean we should not talk about boosters. We must plan and figure out who will get boosters, what vaccines will be used as boosters and when to administer them.

TD: What are India’s options for a booster dose?

SJ: Currently four vaccines have been approved in India — Covishield (90 per cent in circulation), Covaxin, Sputnik V and Zydus Cadila. Our capacity to make Covishield is high. Our capacity to make Covaxin is reasonable and increasing.

Somebody who got two doses of Covishield will not benefit very much from the third dose of Covishield, owing to the nature of the vaccine.

Covishield is made using a virus that causes the common cold in chimpanzees, which is used to make the COVID-19 virus spike protein. So, when you have given two doses of Covishield, you are not just raising immune response to the spike protein, you are also raising immune response to all the chimp proteins in the vehicle virus that are greater in number.

So, if you keep on giving that vaccine, you are preferentially boosting responses to the chimp virus proteins and not the COVID-19 virus spike protein.

The Sputnik V vaccine also uses a similar adenovirus.

Hyderabad-based Biological E’s Corbevax and Serum Institute of India’s Covovax — both of which are protein-based vaccines — are India’s best bet for a booster shot. They can be produced in large amounts and are perfect for booster doses.

In people who got Covishield, for instance, a protein vaccine will selectively boost just the spike response. Between the two companies, they can make about 1.5-2 billion doses annually.

Phase 3 trials have been done for both the vaccines and the data is with the regulator. We will have plenty of vaccines to give as boosters and also to maybe give as primary immunisations if they are approved.

TD: We have already experienced six contagious crises since the start of this century. How do you think a post-COVID-19 world would be? Do you see more infectious threats coming up? 

SJ: It does seem like infectious diseases are emerging more frequently now than they used to. Part of it could be because of our ability to detect their emergence better than we used to.

But I don’t think it’s just that. We are playing with the environment. Most infectious diseases start from animals and when the virus jumps into humans, they cause diseases.

As we increase interaction between wild animals, domestic animals and humans, these viruses will keep on jumping. By deforestation, we provide that opportunity. Much of deforestation happens to clear land for agriculture and for human habitation and that brings the forest closer to humans and domesticated animals.

The Nipah virus in Malaysia jumped from a bat into a pig that was on a farm next to a forest. The forest had been cleared for palm plantation. Bats started roosting on fruit trees in the plantation, their droppings and half-eaten fruits were eaten by pigs that got infected. The virus then jumped to humans.

Several diseases are spread by mosquitoes. As temperatures rise due to global warming, mosquitoes can survive at higher latitudes and can therefore spread disease to a larger population.

It is estimated that by 2080, more than 1 billion people, mainly in northern Europe, will have their first exposure to a mosquito-borne disease.

These examples underline the important role played by ecological practices.

Down To Earth