COVID: 'Treatment gets very challenging'

'When you are on these drugs, there is a possibility that you come to the hospital late, just by virtue of the fact that you believe that things are going to turn around, because you are on all these medicines.'

During the brutal second wave of the COVID-19 pandemic, at P D Hinduja Hospital, northcentral Mumbai, Dr Lancelot M Pinto distressingly saw many suffering patients brought in -- some of them, heartbreakingly, were very young -- who had mysteriously worsened rapidly from the disease.

Or there would be seriously ill patients, who arrived too late, already in later stages of deterioration.

Some of them would eventually die.

In both situations, he ultimately traced the cause back to inappropriate prescriptions.

Prescriptions that had unrequired or excessive drugs. That can directly or indirectly cost a patient his life.

The respiratory specialist and epidemiologist, who received his qualifications from Lokmanya Tilak Municipal Medical College, Sion, northcentral Mumbai, and McGill University, Montreal, Canada, has through social media, been dutifully, diligently campaigning to increase awareness about the drugs we do not need to survive COVID-19 and "disseminating the right kind of information" on the ones we do.

His has been a strong voice too in lobbying that the Indian Council of Medical Research radically rationalise its guidelines for COVID-19 treatment, that had many unrequired drugs.

• PART I: 'You don't need any of these 10 drugs'
• PART II: Received Both Doses? Be Careful Please

"When we sometimes ask them: 'Why have you come in so late? Why didn't you come a day or two before?' and they often tell you 'We were on this drug. We thought we were possibly getting a little better. We thought we would wait a day or two for the drug to take its effect'," Dr Pinto tells Rediff.com's Vaihayasi Pande Daniel in the final part of the interview.

There have also been so many vitamins prescribed during this pandemic.
Can over-prescription of vitamins (and minerals) harm us? We know about the dangers of excessive intake of oil-soluble vitamins, but other than that?
There's also this theory that black mucor has risen from an excessive intake of zinc.
But I don't think there's much conclusive information on that yet.

The dangers could sometimes be subtle. There's this false sense of security that you get from it.

This is obviously in the domain of speaking hypothetically, but let's say a person, who takes a bunch of vitamins, doesn't wear his mask as seriously as he otherwise would, because he thinks that he is protected by these vitamins.

And that's possible. Human behaviour works in interesting ways, right?

Like steaming? Everyone feels protected from COVID-19 because they are steaming*?

Exactly.

The thing with drugs especially, is that we are at the receiving end at the hospital. We have noticed there are a lot of individuals, who are on drugs, like favipiravir (which Dr Lancelot has stated in Part I of the interview does not work) for example, come in relatively late, because there is this constant belief that tomorrow will be better. 'I'm on this drug. I'm taking nine tablets in the morning, nine tablets at night, which is an expensive drug as well, so it must be doing something'.

Maybe had they not been on those drugs, they would have come to us at a slightly earlier date. We find some of them come at a very late stage, when the oxygen levels have already plummeted and they are in a pretty bad state.

When we sometimes ask them: 'Why have you come in so late? Why didn't you come a day or two before?' and they often tell you 'We were on this drug. We thought we were possibly getting a little better. We thought we would wait a day or two for the drug to take its effect'.

That's the other danger. The sense of hope that things will turn around, by virtue of the fact that you're on a certain drug -- that might cause the person to come late to the hospital, later than they would have otherwise.

Zinc, as you mentioned, it's interesting, a friend of mine was telling me that apparently, people who grow mushrooms, use zinc in the soil, in the spawn to help the mushroom grow.

Mushroom is another kind of fungus like mucor?

Yes, exactly. So apparently, fungal growth being enhanced by zinc is a very real thing, you know? So, that's interesting as well.

And what about the secondary effects? What about all the packaging that goes into all these crazy amounts of vitamins that are being sold (during the pandemic)? What about all the waste that is generated out of that? At a macro (level) you have to think about all that as well.

To summarise, number one danger is this false sense of security when you are using these vitamins prophylactically. And if that causes you to compromise on preventive behaviors, that's a problem.

Number two, is, as part of treatment, when you are on these drugs, there is a possibility that you come to the hospital late, just by virtue of the fact that you believe that things are going to turn around, because you are on all these medicines.

Any thoughts on how black mucor has risen?

If you look at the CDC report, which was just published, last week, from India, which is about close to 300 cases, it does look like a significant proportion of individuals did have diabetes.

It looks like about 20 per cent of individuals were newly diagnosed. So, they weren't aware of the fact that they had diabetes.

We know that the SARS-CoV-2 virus (responsible for COVID-19) itself causes your sugar to rise. People have speculated on different mechanisms. There are receptors on the pancreas to which it (the virus) goes and binds apparently.

The uncontrolled sugars are clearly a contributor. Now, whether that's because a person had pre-existing diabetes, or whether the virus contributes to the high sugars, that could be multifactorial.

They found that in those individuals, who did not have classical risk factors, I think, two-thirds of those individuals received inappropriate doses of steroids -- either the doses were too high, or they were given for a too prolonged period.

The causes are obvious. In a majority of individuals, these three things: the virus itself, sugar and steroids would possibly explain (the occurrence of) mucor in a majority of individuals.

Now, there may be a minority of individuals in which it's not that straightforward, and there are other contributing factors.

People have been speculating a lot about it. People have been looking for all sorts of reasons, from industrial oxygen, to the water being used to humidify the oxygen.

I think, for a majority of individuals, you don't need to speculate beyond these three -- the virus, sugars and steroids.

What's your take on the revision of the ICMR COVID-19 treatment guidelines? Why did it take so long? It's going to take a long time for these drugs to go off prescriptions?

Since this is a disease that people are so scared of, they would rather take more, than take less (in terms of drugs).

Once a drug gets out there in the field, on people's radar, it's very difficult to take it off, because people were very happy to add more drugs to that list, than to subtract, right?

I think, we really need to work hard as soon as a drug gets launched.

Obviously, there's a market. There's a pharmaceutical company, which has high stakes in making sure the drug is sold to maximum number of individuals. There are definitely going to be subtle or overt ways in which drugs are going to be pushed.

That's part of practicing medicine. There are ways in which -- I wouldn't say incentivize -- but people (pharma people will approach doctors and) will advertise their drugs, people will subtly overstate the benefits of their drug.

Before that happens, before the wrong word gets out, we (doctors) really need to hit hard, in terms of disseminating the right kind of information.

For instance, within a week of the antibody cocktail** being launched, I put a thread (on Twitter) out there -- these are the details, this is when it's supposed to be used.

If you look at the headlines when the antibody cocktail got launched, the headlines everywhere said life-saving therapy. It saves lives in 70 per cent of individuals.

Then there was this headline which said: 'First patient to receive antibody cocktail gets discharged', which is as distorted as it can be. The person was admitted to get the antibody cocktail. Clearly, he is going to be discharged once he receives the cocktail. Whether the cocktail helped, or not, will be determined two weeks down the road. Deterioration can happen after two weeks.

A headline which says that the first individual to receive the antibody cocktail gets discharged, gives the impression that he got better, got discharged and it really worked for him.

To answer your question (about revisions of ICMR guidelines), yes, it is coming late. And it's going to take a lot of effort to make people stop doing what they've been doing for the past one year.

People are still prescribing plasma. As recent, as two days ago, I know somebody who was given plasma inappropriately.

It's not going to be easy to undo what has been done.

Why did the pandemic in India give rise to this whole phenomenon of handing out doxycycline, azithromycin and antibiotics, left, right and centre?
I have not seen a single prescription of someone who had COVID-19, where it didn't figure.
My daughter had a COVID-19 scare. She was promptly prescribed doxycycline. It's a different matter that I did not give it.
Why did the administration of doxycycline or an antibiotic become synonymous with COVID-19, a viral disease?

(Laugsh) I wish I had an answer to that.

But azithromycin is a very popular antibiotic to begin with. It's prescribed indiscriminately, without much thought at all.

Most of my patients, who come to me for the first time already know the drugs. They don't even wait for a doctor's prescription. They just go to the chemist and ask for azithromycin. It's that blatant.

For every second sore throat, azithromycin is just popped, very often without a doctor being part of the picture. It's a very popular antibiotic. That's one thing.

The second thing is that there were initial proponents for it. People, who said that the combination of hydroxychloroquine and azithromycin is going to get rid of this pandemic.

There was this French series (of messages) and there was a guy in New York. Those messages went viral on WhatsApp. Everybody was forwarding them.

I can't remember the name of the New York guy. But the French guy was Didier Raoult (a French microbiologist) who was the proponent of hydroxychloroquine.

It started off with hydroxychloroquine and then there was this US guy, someone in New York, if I remember, who claimed he had this mass series of patients, and with just the combination of azithromycin and hydroxychloroquine none of his patients deteriorated. It went viral.

Already azithromycin was a drug that people didn't hesitate to prescribe. And combined with this kind of messaging, it made it easier for people to prescribe.

Now where did doxycycline come into the picture I really don't know!

What about steroids? Even young people with very mild cases of COVID-19 are being given steroids, right at the onset of her illness. What kind of harm can that cause?

That was quite shocking. The number of people who we saw receive steroids very early in the disease.

And at the receiving end, at the hospital, we saw a number of people, who didn't fit the profile of the ones who should have deteriorated, coming in needing oxygen, and a lot of them had received steroids.

At the start of illness, you have this profile of high risk -- like who is relatively more likely to deteriorate.

This is clearly anecdotal -- we have not analysed this data -- but I've seen a bunch of patients, now, who did not fit that profile, and yet deteriorated. And when you looked at their prescriptions, you realised they were given high doses of steroids.

Any dose, low dose or high dose, but given to them on Day 2 or Day 3!

That's extremely worrying.

The hypothesis is that in the first week you are in a viremic phase -- the virus is multiplying in your body. The reason most individuals - 85 or 95 per cent or whatever the percentage is -- get better by the end of that first week is that your body's immune system sorts it out. Your body's antibodies get into play.

By the end of the first week, if you measure things like IgM*** is elevated already. And that suffices.

When you give steroids in that first week, you're actually suppressing that natural immune response, which was designed to help you and you are letting the virus multiply.

This becomes very problematic, because these individuals naturally deteriorate. Normally when a person's oxygen levels go down, you're supposed to give them steroids at that point. Generally, the oxygen levels drop towards the end of the first week, and that is a reflection of a hyper immune response.

The virus has almost exited the body, but the body is rebounding with this response, which is out of proportion to what is needed, which is it is overly exuberant. At that stage, you need to suppress that immune response by giving steroids.

IMAGE: Dr Lancelot M Pinto. Photograph: Kind courtesy Dr Lancelot M Pinto

But what would happen with these individuals is when they would come to you, deteriorated, and at the end of the first week, you were never really sure whether it's happened because it's an immune response, or the viremic phase has become so bad because of the suppressed immunity, thanks to the steroid.

So, treatment gets very challenging for us.

Are you supposed to increase the dose of steroids further at this stage? Are you supposed to lower the dose of steroids?

You don't know what's causing good and what's causing harm at this stage.

This was a fairly common problem, unfortunately.

We flagged it as early as August last year, even in the first wave. But for some reason, it did not get the attention it deserved.

So, in the second wave, the fact that younger individuals were involved, younger individuals tend to have a stronger immune response, the fever tends to be higher. Plus, this fear of a lack of availability of bed, the fear of the fact that this was a surge of a really high magnitude,

I think the combination of all of that made people prescribe steroids a lot more, and a lot earlier.

*For instance, there are people who don't mask because they are steam inhaling.
**the new REGN-COV2 drug combination.
***Immunoglobulin M occurs usually in blood and lymph fluids and is the very first antibody the body produces to battle a new infection.

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Feature Presentation: Ashish Narsale/ Rediff.com