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'COVID-19 is deadly in 0.1 per cent people'

By VAIHAYASI PANDE DANIEL
Last updated on: October 20, 2020 11:04 IST
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'Some of the longer-term implications of COVID-19 are not related to the virus itself.'
'They are actually related to immune responses from the virus.'

IMAGE: Professor Ravindra Kumar Gupta of Cambridge University was recently honoured for his brilliant work on HIV. Photograph: Kind courtesy Ravindra Kumar Gupta
 

Cambridge physician and microbiologist Professor Ravindra Kumar Gupta is one of six persons of Indian-origin on the latest Time 100 Most Influential People 2020 list.

He received this honour for 'functionally' curing the previously HIV-afflicted London Patient who came to him for treatment in 2015.

The London Patient is the second HIV-suffering individual to be declared 'cured' after the Berlin Patient, proving that there was hearteningly a road to recovery for HIV and the Berlin case was not a fluke.

According to the London Patient, who wrote about him in the Time citation, Professor Gupta was 'thoughtful', 'compassionate' and accomplished and was responsible for using 'stem-cell treatments I received from a donor with a rare gene mutation, which led to my remission' and he was 'humbled' to know the professor.

IMAGE: The London Patient is the second HIV-suffering individual to be declared 'cured'. He revealed his identity earlier this year. He hails from Venezuela, he is of Spanish and Dutch descent and his name is Adam Castillejo. Photograph: Kind courtesy Ravindra Kumar Gupta

Those days many years ago when the mysterious, deadly and untreatable HIV virus popped up on the scene, in the early 1980s, were not that different from the present murky COVID-19 era.

HIV, which causes AIDS, gave rise to an epidemic of fear.

The chilling unknowability of HIV and the scores of deaths it caused to the rich and the poor alike, and populations in every country, brought panic in its wake and changed lives forever.

That situation isn't unlike what the world is facing today as it confronts the shadowy COVID-19.

IMAGE: Timothy Ray Brown, was known as the Berlin Patient and was the first person to have been 'cured' of AIDS. He recently died in California of leukemia at the age of 54. Photograph: T.J. Kirkpatrick/Getty Images

Professor Gupta, who continues to work on HIV, has turned his focus to COVID-19 as well.

SARS-CoV-2 is from a family of viruses of the future and Professor Gupta's years and experience grappling with anti-viral therapy for HIV came in very handy when he joined the army of scientists, doctors and epidemiologists across the globe in the War Against COVID-19.

As he puts it: 'I've spent the last decade studying HIV. The work I've done has been useful preparation for the COVID-19 pandemic, so it felt like the team was in the right place at the right time'.

Professor Gupta is presently studying the immune response to SARS-CoV-2, the virus that causes COVID-19.

He and his team have also reengineered a platform used for HIV testing to use for testing for SARS-CoV-2 and the Samba II machine has been born, which is being used in hospitals in the UK.

Professor of clinical microbiology at the Cambridge Institute of Therapeutic Immunology and Infectious Disease, Professor Gupta studied medicine at Cambridge, did his clinical degree and later his infectious diseases training at Oxford, his masters in public health from Harvard School of Public Health and his PhD in virology from University College London.

He is also attached to Africa Health Research Institute in Durban, South Africa.

In Part I of an interview to Vaihayasi Pande Daniel/Rediff.com, the soft-spoken, modest-mannered Professor Gupta speaks of the parallels between HIV and SARS-CoV-2.

There is a lot of similarity between the advent of COVID-19 and HIV.
COVID-19 when it began, first appeared to be a lung disease and now doctors are talking about neurological symptoms, heart damage, liver damage etc.
But the havoc it wreaks has been a gradually emerging picture.
That was that how it was for HIV.
You have said HIV is an enigmatic disease.
It is still early stages for COVID-19, but does it also seem enigmatic?

It certainly is enigmatic.

I think, it's going to remain that way.

That's one of great parallels between the two diseases.

This is not a typical respiratory infection, where you get a lung disease and then you get better. Or you die.

It's actually a multi-system disease.

Not that many infections cause multi-system diseases, especially viruses in this sort of way.

I definitely think there are huge parallels between the two.

The HIV virus never leaves your body.
So far it seems, it does not look that way for the virus that causes COVID-19.
Being a respiratory virus, experts say it does not linger?

In some people you do get viruses coming out of the patient for weeks, sometimes months.

But yes, in general, it disappears.

Because it's not a retrovirus, it doesn't have the ability to make DNA and therefore it can't become part of your chromosomes.

So, it is much less stable.

And therefore, it's not going to be a lifelong thing.

We think that some of the longer-term implications of COVID-19 are not related to the virus itself.

They are actually related to immune responses from the virus.

Could you elaborate a little bit about what you mean by immune responses to the virus?

There is some speculation that actually, sometimes what's happening is that certain cells in the body are becoming overstimulated by either the virus or something the virus is doing -- the inflammation that is created by the virus.

And this creates a kind of chain reaction, which is then difficult to control.

That's not really been proven yet, but that's one of the thoughts as to why some people continue to get sick, even though the virus becomes less detectable or disappears from the nose and throat.

And it potentially could be related to the fact that some people have developed blood clots, for example, in the lungs, or in other places.

That could be directly due to the excessive inflammation.

Blood clots is not something that happens very often with infections.

It seems to be something that might be somewhat unique to COVID-19, something in the way that it stimulates the immune system.

There are two parts to the immune system.

One part to the immune system is something that cells do.

Every cell is programmed in a way to detect foreign invaders.

That's innate immune response.

There is a quite strong innate immune response, as far as we think.

But then there is the other side, which is antibodies, the cells which are specialised to deal with a specific pathogen threat.

And so, both sides can be triggered.

Maybe antibodies -- although we think they are protective -- there's a speculation that antibodies themselves may be involved with some of this.

But that's not been proven yet.

IMAGE: Professor Ravindra Kumar Gupta at work. Photograph: Kind courtesy Ravindra Kumar Gupta

Are the antibodies to COVID-19 lasting?
How long does the immunity to COVID-19 last?
Can the cellular type of immunity be more lasting?

Well, we know that in patients even with mild or severe disease, you do get cellular responses, antibody responses, and T cell (a type of lymphocyte) responses to the virus.

It's not clear why some people get better and why some people get worse.

That they still really haven't figured out.

But when people get worse, it does lead to damage to the immune system.

For example, your T cells die down and can become very low.

And it's further damage to the immune system or immune response.

In a way that's kind of similar to what HIV does, which is just destroying T cells for example.

And to make you more susceptible to infections.

We haven't seen any evidence and there's nothing obvious in terms of whether COVID-19 makes you more susceptible to other infections yet.

It is something people are looking at, because if you can lower the levels of T cells in the blood it will have some consequences.

Some people take quite some time to recover their blood cell counts.

Supposing you are suffering HIV, are you more susceptible to COVID-19?
And if you have suffered COVID-19 are you more susceptible to HIV?

It is not clear at the moment.

There was one report from South Africa suggesting that for patients with HIV, who have got COVID-19, it is worse clinically.

It's not published yet, so we haven't been able to properly review it.

Of course, anything that damages your immunity will reduce your ability to fight infections. We know that.

We can see already from the COVID-19, that people with damaged immune system, they do worse than those with normal immune systems.

New facts are coming in all the time on COVID-19.
But it is very evident that it has brought a lifestyle change.
When HIV first arrived, it was memorable for bringing a lifestyle change too.
In your view, does COVID-19 look worse than HIV?
It's a much bigger lifestyle change with COVID-19 and it's a public health nightmare.

Clearly, it is worse.

Because it is spread by the respiratory route, not the sexual route, its infectiousness is much higher and its probability of transmission.

So, yes, it is much worse from that point of view.

Once you have the disease, of course, HIV was a deadly disease in 90 per cent of people, or 95 per cent of people, whereas COVID-19 is deadly in 0.1 per cent people -- 1 in a 1000.

Your chances of surviving are much higher in COVID-19.

But now, of course, with HIV, and treatment, we have, you know, very high survival rates of HIV now.

The death rate from HIV is lower than it used to be. For sure.

I guess for COVID-19 we will develop treatment eventually that will enable us to treat people properly.

IMAGE: An illustration of a pseudovirus. Photograph: Kind courtesy Ravindra Kumar Gupta

In an interview, on your Web site, you mention using pseudo viruses to study COVID-19.
How exactly does that work?

We are trying to understand, whether people have antibodies in their blood to the virus.

If you want to use the SARS-CoV-2 virus (which causes COVID-19), you can use the whole virus, the fully infectious virus.

But that is quite dangerous.

You have to do that in special containment (areas/procedure).

And it's more complicated.

We are doing that as well, but it takes much more time.

A much simpler way of testing some things is in a modified pseudo virus system.

For example, we make our special viruses which are actually HIV on the inside and coronavirus (SARS-CoV-2) on the outside.

These are very, very useful system for testing for example, properties of the spike protein, the protein which is on the surface of the virus, of the coronavirus (SARS-CoV-2).

Most of the antibodies that we develop in people are directed against the spike protein.

If you want to test whether there are antibodies in someone's blood, you can make these pseudo viruses and mix them with the blood of a person and you can look for the ability of those antibodies to block infection by the virus in the cell.

If there are antibodies in the blood, they will block this virus from infecting the cells.

 

SEE: Cambridge physician and microbiologist Professor Ravindra Kumar Gupta talks about shifting the focus of his work from HIV to COVID-19. Video: Kind courtesy Ravindra Kumar Gupta

 

Since there's really no treatment yet for COVID-19 I understand you and your team have been looking at types of treatment for COVID-19s What have your studies thrown up so far?

Well, initially, we were interested in looking at drugs like lopinavir, etc because we had a lot of experience with them.

But really, by the time we started thinking about the experiments, a number of groups had already showed that it didn't work for patients.

So, there was no point really doing any in vitro work.

We were also were looking at antiviral, anti-inflammatory drugs like azithromycin.

We are moving towards trying to understand inflammation from COVID-19 in macrophages or these particular white blood cells that are part of our immune system.

We think that these cells are going out of control.

And if we can understand why, then there are lots of drugs available to treat parts of the inflammatory response.

Then we'll be able to say, that this particular drug or that particular drug should be used.

So, so that's where we're going with this.

We're trying to understand the disease process in order to figure out which the best drugs would be.

You can't replicate these things in the test tube very easily -- understanding how disease happens.

Is that the kind of approach taken when you were working with HIV?
Is it similar?

HIV drugs developed in a slightly different way.

People developed molecules to bind the HIV protein using computers.

The same is being done for the coronavirus (SARS-CoV-2).

It is just that it takes time for that to come to fruition.

The problem is, by the time they figure out what the right molecules are, they have tested it in animals and then humans, we know it might be a little bit too late.

So that's why people have been trying to use drugs for different diseases against coronavirus (SARS-CoV-2) in order to figure out if they can find an existing drug which is effective.

To date there isn't really anything that effective, except remdesivir, which is a little bit effective, but not hugely.

In Part II of the interview with Dr Ravindra Gupta, he speaks about the COVID-19 testing machine Samba II that he and his team created.

Feature Presentation: Ashish Narsale/Rediff.com

 

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The War Against Coronavirus

The War Against Coronavirus