Mumbai: "Deaths from Covid-19 are amplified by any mistakes we make," said S. Vincent Rajkumar, an oncologist and professor of medicine at the Mayo Clinic in the United States. The shortage of health resources, such as oxygen, and the overuse of medicines, such as steroids and antibiotics, have exacerbated problems from the Covid-19 pandemic in India, he elaborated.
Of India's billion-plus population, over 315,000 have been officially reported as having died of Covid-19, even as widespread reporting shows that these numbers are underestimated. The only way out, said Rajkumar, are Covid-19 vaccines. Until now, India has fully vaccinated about 43 million people and over 160 million have been given the first dose of the vaccine, still too low to protect most people against the disease, explained Rajkumar.
We asked Rajkumar, also the editor-in-chief of the Blood Cancer Journal, what India can learn from the first and second wave of Covid-19, which is now abating in several parts of the country, to deal with a possible third wave in the future.
Within the Covid-19 pandemic, India is also facing the epidemic of black fungus or, mucormycosis, which suggests an overdose of steroids. We asked Rajkumar, who completed his bachelor of medicine and surgery (MBBS) at the Christian Medical College in Vellore and at Madras University, about doctors pressured to overmedicate.
Edited excerpts from the interview:
Before we get to the way forward in this pandemic, my first question is why are you following the India situation so closely?
As you know, I was born and brought up in India. I did my medical school here and all my family lives in India. I mean, my parents live there, my brothers, my sister. I have a huge number of friends and relatives so naturally, we are following the situation very closely. A lot of people have reached out to both myself and my wife, who gives advice to patients as well as counsels physicians on strategies to treat.
In the US, there was a huge spike in cases and a huge number of deaths. Now, it is easing off, very likely due to vaccination, which is faster in the US than in many other countries. In India, the second wave is easing but not necessarily because of vaccination, except in one or two places. How do you look at these two situations at this point?
In the US, we got hit with at least three waves in the last year (in 2020), and each time, the wave was suppressed with a lockdown or a social distancing containment measure. The most recent one, I think, is because of the effect of vaccines, which started in early December. And by now, half the adults in the US have had at least one dose, and a majority of patients who are 65 years and older have been fully vaccinated. So, this time we are seeing the lowest number of cases in almost a year, deaths are coming down and things seem to be under control. There is some hope now, this time, as restrictions are relaxed, the fourth wave will not happen again because most of the population would be vaccinated.
In India, you had a really significant wave last year and somehow, as social restrictions were lifted, the cases continued to drop. But progressively, people got more and more confident that the pandemic is over. This time the cases are very high and it is coming down but you have 90% of the population still not vaccinated. So, the difference is that if you relax, things will come right back because the population is still susceptible.
And you say that because you feel the virus is fundamentally alive and kicking everywhere?
Yes, the virus--the new virus-- most of us are not susceptible to it [in the US]. Even if half of India has had Covid-19 already, that still leaves another 700 million people susceptible and that would be a huge number of deaths. And so, we have to assume that either we have had Covid or have Covid or we are going to get Covid and we have to protect ourselves. The only way out is through vaccination of at least 70-80% of the country.
You have been actively campaigning about the nature of the administration of medicines and prescriptions in India and specifically the use of steroids. Now, I am sure you understand the Indian context, and why doctors overprescribe. How do you see us coming out of that and what could be some solutions?
You have to step back and see why this enormous second wave, almost like a spike, happened. As I mentioned, it happened because, one, there was relaxation of social distancing [and there was] crowding. That was a key problem. Number two, mask compliance became very very low and that allowed the virus to transmit very easily among people and at a higher viral dose. Because if you are not wearing masks, when you do get exposed, it is a higher viral dose. But the third factor is that the virus itself became more transmissible, potentially more virulent. And so, you are faced with a triple threat here. That alone is going to cause a huge number of deaths but when it all happens at the same time, you have a really crushing blow to the healthcare system which is now facing an onslaught of cases.
Deaths from Covid-19 are amplified by any mistakes we make or any shortages of healthcare resources. What would have been a 2% mortality is now a 20% mortality and that is the same thing which happened early on in Lombardy and New York when the cases came very fast and all at the same time. So, what is happening now is that you have shortages of beds, shortages of medication, oxygen, but then we also want to do something [to treat patients] and that has led to the overuse of steroids and antibiotics when they are not necessary. What happens then is that you get complications of these which could be deadly serious and cause more problems; everything from secondary infections with bacteria to black fungus infection and other problems. I think you compound what was already a bad situation with a more transmissible virus with all these other things that happen with the healthcare system.
Right, so if you look at India, many of us over the years have been over-prescribed antibiotics and we have taken them for diseases we should not have [done so for]. Now, when faced with a situation like Covid-19, will changing the strategy help? For instance, suppose the doctor says that no, do not take any antibiotics, do not touch steroids at this point for at least the first eight days and stay put, but the patient says I have always taken antibiotics in my life and you know, maybe it has worked. So what do you do?
Well, here is the thing, we have to make sure that physicians are totally clear on what steroids can and cannot do. Steroids are not antivirals; they actually promote viral growth because they suppress the immune system, they kill the plasma cells that help you fight infection. By giving it early, yes, the fever will go away, and the patient might feel better, but behind the scenes, the steroids are actively encouraging the virus to replicate and cause problems and you will end up with worse outcomes.
Number two, there is a right dose [of steroids]--too high a dose and it becomes toxic. I have seen steroids prescribed at very high doses. Much much more than what the Recovery Trial shows. Sometimes five times more. And thirdly, (steroids are) given for a very long duration. Unless somebody is on steroids for two months or something, you do not need to taper the steroids, it is five-10 days and stop. But people are giving steroids for 5-10 days at high doses and then continuing them week after week after week. That will suppress the immune system and initially, it will promote [the] Covid-19 [virus] to grow and later on, it will promote black fungus and bacteria to grow. This is not an antiviral treatment, it is used to suppress a very active immune system that is causing lung damage and you need to do that only if the oxygen level is less than 92% and then only at equivalent of six milligrams of dexamethasone for 5-10 days and stop. Beyond that, if you have a problem, it is not due to Covid or Covid inflammation, it is something else so steroids will not fix that.
You are saying that even if a patient is in some ways used to taking an antibiotic at the first sign of trouble, he/she should be counselled not to take it. I am just wondering how can doctors do that better, rather than trying to fight the other battle and treating problems caused by an overuse of medicines.
I practiced medicine in India before I moved to the US. So, I know how the patients are and how things are. I do not want to blame the patients here because the patients are not aware of the pros and cons of antibiotics or steroids. We are. And I have seen prescriptions that routinely include the antibiotics azithromycin or doxycycline, including in guidelines. And that is completely unnecessary and it will promote bacterial resistance and it will promote infection with drug resistant bacteria. So, all we need to do is counsel the patients from the beginning that this is a viral infection, steroids are going to make it worse, antibiotics are not going to have any effect on it.
Very few patients with Covid in the first week or so get a secondary bacterial infection. So, we do not need to give it. Give a prescription for what works--that will be paracetamol for fever--and just tell them to watch their oxygen concentration with a pulse oximeter. And if they feel short of breath, very short of breath, particularly while walking, and a pulse oximeter shows a lower oxygen concentration, that is when they seek medical help. That is when steroids might help. Antibiotics are used only when there is a real indication of a secondary bacterial infection.
And the point is that even in normal times you should not be overmedicating yourself. It is not about Covid.
Absolutely. Forget Covid, we are all aware about drug-resistant bacteria being a big problem in India and that is clearly related to the widespread use of antibiotics that have a very broad spectrum. You wipe out all the susceptible bacteria and then you allow resistant ones to grow. That is why you have, in hospitals, drug-resistant bacteria that are resistant to all the antibiotics that we have. Same thing with fungi, you have Candida that is resistant to all the anti-fungus [medication]. So, you want to be really judicious in the use of antibiotics, antifungal agents so that when you need them, they are there for you.
You have spoken about how to administer dexamethasone and your own lessons in treating patients. Walk us through that.
Dexamethasone is a drug that I have studied for more than 20 years because we use it as a treatment for multiple myeloma--cancer of the plasma cells. Now, plasma cells are the cells that make antibodies; when you get a vaccine, plasma cells make antibodies and that is how you get protection from Covid-19. We use steroids in the oncology field to kill these plasma cells; they are very powerful weapons to suppress the immune system. Early on, when I started my career, the amount of steroids we used even for a cancer like multiple myeloma was too high. We did a study where we compared high dose versus low dose only to see that the low dose gave the same benefit with less side-effects. What we found was beyond our imagination--that the low dose actually saved lives. We had 10% people die in the first year just from the high dose of steroids so we have given a lower dose of steroids for all these years--15 years plus--in myeloma as a result of that trial. I know how bad these drugs can be. When used appropriately for about 5-10 days at six milligrams, it works really well and that too only when the patient is hypoxic [has low oxygen levels, in the case of Covid-19]. [If] you use it at a higher dose, you use it for a longer period of time, it will cause everything from higher risk of blood clots to higher risks of secondary infections to black fungus. So, just keep that lesson in mind.
The second point is about giving an equivalent dose of an alternative of dexamethasone. If there is a shortage of dexamethasone, people are using solu medrol, methylprednisolone or prednisolone. And the equivalent dose is 32 milligrams of solu medrol or methylprednisolone once a day. But routinely, I see twice a day or even 200 or 500 milligrams of methylprednisolone. That will really suppress the immune system more than you need it to.
I know you have given us some very specific medical prescriptions. Now, each patient is different and therefore, a physician should also be adjusting to that patient's physiology and so on.
That is where you need to know how powerful these medicines are. Six milligrams of dexamethasone is a big dose. You do not gain anything more by giving twice that amount or thrice that amount to anyone unless they have cancer of some kind that you are trying to deal with. So, just to recognise that for most patients in India, I think even six milligrams may be too much because that was based on body weights that are seen in the West. Even for the diseases I deal with we have generally used lower doses of steroids. We use 40 milligrams in the US for myeloma treatment. We recommend sometimes, for Indian patients, only 20 milligrams. So, for the body weight and body surface area of Indian patients, for most of them, even six might be too high. What it also does, I think this is important, it will universally increase the blood sugars. And there is a lot of diabetes, a lot of unrecognised diabetes in India. In a crunch, where everybody is fighting for oxygen, the last thing people check is the blood sugars. And when you are putting patients on steroids and particularly, higher doses, [blood sugars] are going to go up as well. And that is the number one reason for mucor.
Given your understanding of how this disease has progressed and the treatments that the medical fraternity has performed, what is your sense on how a third wave could be different? The second wave in India has affected more younger people, it showed that we were overdosing when it came to steroids and are facing the consequences of that. And of course, the behaviour of the virus, its transmissibility and infectiousness. What would you say could happen in the third wave, based on your understanding and experience?
I think that the fundamental lesson that I learnt last year--because we all made mistakes, including me--on what was going on in India, was that [we wrongly believed that] somehow Indians are protected from the virus due to pre-existing Covid-19 immunity of some kind. But really, the reason the numbers came down in India with the first wave was because people were scared of the virus. They did take precautions, they did wear masks and there were lockdowns, so that really got the wave under control. This time the wave was much worse and I have no idea how many people were affected each day as the counts are hard to combine. And, again, every state is in lockdown and the cases are naturally coming down, particularly in the urban areas, the cities. We do not have insight from the rural areas. But keep in mind, this is coming down because of social restrictions, because people are not coming in contact with other people and because people are wearing masks.
At this point, the third wave is fully in our control. It will happen only if people relax too early, it can be avoided or it can be minimised if people understand they are still susceptible until they are vaccinated. And so, the real key is, eventually, when the test positivity goes to 5% or lower, as restrictions are relaxed, people still need to be educated that you are susceptible, you will get Covid, and there will be a third wave unless you wear masks and you avoid crowds and do not invite people into the house that you do not need to see. And, just keep your distance till you get your vaccine dose. This time at least, there is a way out of this, which is vaccinations. As vaccination rates go up, then you feel more and more free.
The third wave could be as bad as the second wave and affect younger people, provided we abandon all these principles and just start living life as before. It is really all in our hands how the shape of the third wave, how high it will be and how much more people will be affected. Depends on what we do, both from the government standpoint, in vaccinations and making sure everyone has access to it, and quickly securing enough vaccines from wherever. From the public standpoint, in maintaining the guidelines of social distancing and masks.
Last question: What should medical practitioners bear in mind? They do know their job but they are the ones who are in intimate contact with patients and perhaps, feeling the brunt of patient and family pressure on prescriptions and medications. So, how should they be navigating the next wave?
Yes, and it is very, very hard… [there are] heart-breaking stories from Indian physicians. The number of Indian physicians who have lost their lives is really worrying and heart-breaking. And, I know that no one can function when you have 20 patients show up at the same time or when you are the one person manning the ICU [Intensive Care Unit] with so many people critically ill. So, I do not think they could have done anything better, because [even] in a resource-rich country like the US and [city such as] New York, we had 10-20% mortality in the first wave when the resources were all stretched.
So really, the question is, if we can build up [resources] when the cases are down, particularly hospital beds, ICUs, ventilators, oxygen units, so that if and when a third wave comes, physicians will not be so stressed--that is the first thing. The second thing is please avoid unnecessary medications and counsel your patients that all they need… like 90% of Covid patients will recover with just paracetamol, staying at home and waiting it out. Only when there is hypoxia, use steroids and seek medical care and oxygen. That is all that is needed. There are very very few specific treatments that work for Covid, a number of the ones that we are touting are only because we want to do something, but they are all double-edged swords. They come back [in the form of other problems], they are not proven and I do not think we need to worry about all these extra drugs.
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