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What approach should we adopt to treat Omicron?

Tamil Nadu, Chennai, 23/01/2022 : For City : Staff nurse wearing a Personal Protective Equipment (PPE) attending a Oxygen support Corona virus positive patient for admission at Omandurar Government Medical College Hospital, Chepauk in Chennai on Sunday. Photo : Jothi Ramalingam .B / The Hindu

Tamil Nadu, Chennai, 23/01/2022 : For City : Staff nurse wearing a Personal Protective Equipment (PPE) attending a Oxygen support Corona virus positive patient for admission at Omandurar Government Medical College Hospital, Chepauk in Chennai on Sunday. Photo : Jothi Ramalingam .B / The Hindu

With Omicron becoming the dominant COVID-19 variant in the country, and with its reputation of being a ‘milder’ form of the disease, there is a debate raging on what treatment methodologies are appropriate. Should we adopt a conservative line or an aggressive line to treat Omicron? The responses to SARS-CoV-2 have been changing constantly, whether in the form of treatment or social restrictions. In a conversation moderated by , infectious diseases specialists Dr. V. Ramasubramanian and Dr. Subramanian Swaminathan discuss the question and the challenges of responding to an evolving pandemic. Edited excerpts:

Omicron has a reputation for being ‘mild'. Is this true?

Dr. V. Ramasubramanian: We are fortunate that the current third wave, which is caused predominantly by the strains of lineages of Omicron, appears mild. In other words, the disease is much more rapidly transmissible but disease severity is significantly less compared to the Delta variant. The incubation period is much shorter, the transmissibility is much, much higher and faster, and the disease is mild. The only slight difference I would say is that unlike Delta, which caused milder infections among younger people, we find now that even youngsters have high-grade fever. But fortunately, it settles down in three to four days in most people. Even though Omicron has significant mutations, and it spreads very fast, disease severity is lower compared to Delta.

 

Dr. Subramanian Swaminathan: Delta was an unmitigated disaster for the whole world, not just for us. We do have a lot of symptomatic disease now. We are seeing quite a few of the extremely elderly, especially those with co-morbidities, now coming in with severe disease; my ICU is currently full. And I have quite a few patients who we would classify as critical COVID-19 cases.

And let's not forget that mortality is not insignificant. We call this variant mild, based on the need for oxygen. But having said that, I'm seeing an increasing number of people who are completely miserable due to Omicron because of the fatigue and body ache it causes. I'm seeing a lot of elderly people with mental fogginess. They have loss of energy, some of them tend to buckle and fall, some have had a fall in blood pressure. None of this would qualify as severe disease, but the symptoms in older people can be dangerous.

So, while treating COVID-19, presumably since the dominant strain is now Omicron, do we take a conservative approach or a more aggressive path?

Dr. Ramasubramanian: It’s a difficult question in the sense that there are people who can become sick — for instance, the elderly with co-morbidities can end up very sick. But if you look at the percentage of people who become sick, it's very small compared to the number of people who fall ill and have symptoms, which is significantly higher than what we saw with Delta. So, people who are elderly, have co-morbidities, or people who are unvaccinated can fall ill. But this percentage is very small.

Because [symptoms in] most people settle in three to four days, we have a window of at least five days before we need to react to it. I don't think we should hurry and give something on the first or second day of the infection. So, my advice has been to wait for three to four days. If by the fourth day, the patient is feeling significantly better, which is what happens to most people, they should be fine. But if by day four or five, things are not settling down, the patient is not feeling better, we need to probably act.

Dr. Subramanian: I agree with that. Jumping the gun and running for medicines for every patient is probably ill advised. I think we should be very generous with things like paracetamol. Rest, drink lots of fluids. The [symptoms in] the majority of patients are going to settle very nicely.

Is vaccination helping keep death, severe disease and hospitalisation at bay? Are more children infected now?

Dr. Subramanian: The vaccine campaign has been one of the major victories that we've had in reducing the impact of COVID-19. That is certainly making a difference. The question is, how long does immunity last and how effective is it, especially in the most vulnerable groups? Obviously, the unvaccinated do remain a significant vulnerable group. However, we are noticing that among patients 70 years and above, especially those who have multiple co-morbidities, if the second dose of the vaccine was administered to them more than six months ago, it seems as though it is not protecting them adequately. Those who had received the second dose of the vaccine within the last six months didn't seem to do so badly, irrespective of their age. So, I think there is some value in the booster dose. And I really wish we had started administering the third dose earlier.

And yes, we are getting a lot of children and adolescents coming in with fever. But thankfully, the majority of children do not have a problem. Just watching symptoms and providing symptomatic therapy is enough. My colleagues are telling me that children are coming in with fever-induced seizures. It’s too early for us to say if there is a real link with COVID-19 or is just happenstance. But that's something that we need to observe very carefully.

Dr. Ramasubramanian: With regard to vaccination helping, it is spot on. But we have seen that as the antibodies wane, there is a higher risk of picking up Omicron. Now studies have shown that if a booster dose or a third dose had been given to people, they would have stood a lower chance of having symptomatic Delta virus infection. If your immunity after two doses was about 80-90% and went down after six months or so and you were given a booster for the Delta virus infection, the protective efficacy would have gone up again to 80% or 90%. In other words, the booster would have brought up your level of protection from symptomatic disease to 80-90%. But with Omicron, protection from the third dose was actually only about 50-60%. So, the booster dose was not as effective for Omicron in preventing symptomatic disease as it was with the Delta variant. This has been clearly documented.

But if you look at severity, which warrants hospitalisation or complications and death, even for Omicron, the third dose actually did very well. The necessity for a booster in preventing serious infections, whether it is Omicron or Delta, is very well established. But one thing I would like to add is, even though we are looking at administering three doses for most people, I think the priority is to ensure the two doses are given to the entire population.

How do you deal with the constantly changing goal posts for treatment for COVID-19?

Dr. Subramanian: The process of data gathering is not necessarily linear or streamlined. If we look at medicine as such, we have evolved our way of looking at the data and understanding the science of it in a much better way right now than we did, say, 50 years ago.

When you have a new problem, and a new molecule, and new drugs, if there is one study done very well with enough numbers, it may be fairly useful in concluding the path ahead. But we need to do studies in different settings and populations, and then decide how it works. During an evolving pandemic, what is true in one wave may or may not be applicable in the second wave, especially when it comes to antivirals. That’s exactly where we’re going.

The third thing is that it also depends on the kind of population we are looking at. For example, a lot of the studies, on the basis of which we have got approvals for various drugs, were done on people who were unvaccinated. But now, nearly all the people who are coming in are vaccinated.

When we talk about COVID care, there are two parts to it — antivirals and the treatment of hypoxia. And the good news is that for the second part of the treatment, which is treatment of severe COVID-19, which is basically lung injury, the data on treatment are fairly clear. The antiviral use is a moving target and it changes based on where you are and who you are studying.

Dr. Ramasubramanian: Medicine is constantly evolving. But what we have to understand is that there are two issues. One is medical and the other is advocacy. If you look at the medical evidence, this should be based purely on science, purely on randomised control studies. But these kinds of trials and studies take time, you cannot be waiting around to come up with advocacy. The advocacy will involve political issues, logistic issues, such as the question of lockdown.

In the early part of the pandemic, all kinds of drugs were recommended for all kinds of situations. That has been streamlined. So, we have definitely become a lot better in our approach to handling this crisis. But we need to understand that this situation is constantly evolving. Earlier, nobody was vaccinated; now we have a vaccinated population. So, would the same drugs work? It depends on the population dynamics and behaviour; on the susceptibility of each person to infection, whether they are unvaccinated/vaccinated; on the immune response to earlier infections. And most importantly, it would depend on the variants and how they behave. So, the bottom line is, this is still constantly evolving, and we need to learn along the way.

Is it possible to ensure that certain recommended protocols are implemented across the country?

Dr. Subramanian: It's a pretty complex area. While COVID-19 has shone a spotlight on it, it is happening everywhere else. So, therefore, while the government has had very detailed guidelines on treatment for several diseases, not many doctors are aware of them. There is obviously a problem in education and dissemination, and that needs to be addressed. These protocols should be strictly followed in academic institutions. Only if that happens will we be able to fix the private sector.

Dr. Ramasubramanian: With regard to COVID-19, even with evidence there is a problem because this is constantly evolving and what was true two months ago may not be valid now. In the Indian situation, one more complication is the spectrum of care which is given to the patient, unlike in the U.S. or the U.K., where the standard of care is a very small band and the best and the worst fall within the band. In India, the best hospital is probably on par with or better than some hospitals in the West, but the worst hospitals are really bad. So, it is very difficult to come up with guidelines to cover this entire spectrum of population and healthcare delivery.

Subramanian Swaminathan is Director, Infectious Diseases and Infection Control, Gleneagles Global Hospitals, Chennai; V. Ramasubramanian is Senior Infectious Diseases Consultant, Apollo Hospitals, Chennai


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