Mumbai: India is seeing a dramatic, though not completely inexplicable, rise in COVID-19 cases. The rise is more in states such as Maharashtra, which had 53,000 cases on March 23, 2021. It appears that, like before, most cases are from the more active and industrialised states, epidemiologists say.

With the existing seropositivity in major cities, combined with faster, larger intake of vaccines, as well as wearing of masks and distancing, this COVID-19 peak might not be as problematic as the earlier one, says Rakesh Mishra, director of the Centre for Cellular and Molecular Biology, part of the Council of Scientific and Industrial Research, in this interview.

Tanu Singhal, a paediatrician and infectious disease specialist at the Kokilaben Ambani Hospital in Mumbai, tells us how the second wave is playing out at the front lines.

Edited excerpts:

Dr Mishra, what are you seeing in terms of these new mutations and what are the differences between what we saw a few months ago and in the current big surge?

RM: Mutation is a very natural process of all living beings and particularly these kinds of viruses. For example, the common flu mutates so fast that if we make a vaccine, we will have to change that. The COVID-19 virus is mutating, and we know it from the very beginning. What has happened recently is that because of the UK variant, we have started sequencing more. In this way, we are recording and documenting more variants. The idea is basically that if there is a variant that is emerging or causing an increase in these number of cases or posing any other kind of problems, genome-based surveillance is very very important and particularly for such viruses. And in the country, it has started on a large scale now.

So far, we have found that in Maharashtra particularly there is a double mutant. This one has become more talked about because it is a mutant that is on 452 and 484 positions of the virus and these two mutations seem to be going together in a significant number of cases that have been sequenced. Therefore it comes in the category of VOC--variant of concern.

It is this variant of concern that is being seen in large numbers. But that does not mean that it is causing any trouble at the moment. For example, in Maharashtra you see this variant in 20% [cases], which means 80% of the new cases are because of something else; so certainly, this double mutant is not the cause of the increasing number of cases. Neither is it more clinically troublesome because a number of people are asymptomatic and mortality is lower than before. It looks like this mutant is there, but it has to be watched and recorded and monitored [to know] how much it is spreading and if it is causing anything else. This does not seem to be of much concern at the moment.

And just for the record, I think I had asked you about this in December, Dr Mishra, how many mutations have you now sequenced and chronicled?

RM: I will talk about all India. The number of mutations that are isolated and have been sequenced has reached close to 9,000 now. The number of mutations that are recorded will maybe cross 10,000-11,000, but that doesn't mean there are 10,000-11,000 variants. Most of them [the mutations] are recorded and are of academic interest. They don't have any other clinical consequences, so they will disappear after a while but this double mutant that we just talked about is probably the new one that has emerged and is presenting in significant (20%) numbers, although only in Maharashtra. Elsewhere in the country, it is less than 1%.

Dr Singhal, what are you seeing from your vantage point at the hospital? What are the differences or changes from the previous surges particularly towards the third quarter of last year?

TS: We are seeing an overwhelming number of cases now for the past two to three weeks. In fact, from November-December the number of cases had started coming down, and at some point in February, we thought we would have to close our COVID ward and COVID ICU because there were hardly any patients. But now we are overwhelmed completely--so much so, that there is a shortage of beds in our ICU and in our wards. There are so many people among us staff who hadn't gotten infected in the past six months who are now having infections.

So, I would like to make some observations: First of all, we are seeing the opening up in Maharashtra that has been happening for the past four to five months. It is not that it has recently opened up. Since Diwali, people have been meeting and gathering, not wearing masks properly. But something has definitely happened that has triggered this alarming increase in the number of cases and we cannot attribute it, in my mind, to only the lack of precautions. To me it seems like the virus, whether the mutant or the original, has become more infectious because people are getting infected, whole families are getting infected.

Second, we are seeing people who have been infected in the past, now coming back with reinfections. We have had two cases in our hospital.

Third, we have seen people who have taken two doses of the vaccine and a week or two later are again getting infected. However, the severity of infection continues to remain low. So most of the patients are mildly symptomatic and recover. So I would not say that the severity has gone up, but it is too early to say that severity has gone down. The number of cases is huge, it is even more than what it was.

Yes, but if they are coming to your hospital, that means things have already crossed a certain line, isn't it?

TS: Yeah, so people are coming to the hospital for various reasons--one is some people are genuinely sick, so they are coming. There are other people who are at risk of severe illness because they are elderly and are having fever and it is day three or four, so they feel a little bit unsafe at home and are coming in. We have both kinds of patients. Our ICU has patients who are very sick and our wards have patients who are mildly or moderately sick as well.

Are you seeing any changes or is it the same profile of patients that you were seeing even at the peak in August or September?

TS: We have not recorded any kind of major difference in the symptomatology etc. as compared to what we saw earlier. However, we do find that they respond better to the medication that we give them. In September, we had one or two deaths in a day and then during the lean period, maybe we had one death in two weeks. Now, even with this surge, the number of deaths has not gone up and has remained the same as in the lean period. You have a very small subset of patients who deteriorate very fast and you can't do much about it, but there are other patients who, even after becoming very sick, recover. In the new cases, I would say that even though the number is high, the severity seems to be less.

One of the characteristics of COVID-19's attack earlier was the sudden deterioration that you saw in patients. Are you saying that you are not seeing that sudden deterioration now or not so much, at least in your hospital?

TS: It is not the question of sudden deterioration. It is a question of the percentage who deteriorate. The percentage of patients who become very sick or who need ICU care has continued to remain low. Many patients just have fever and they become sick but then, after seven-eight days, they recover and they go home.

Is the treatment progression roughly the same as before or are you better armed this time? Are there new medicines or new medicine protocols that you are using?

TS: No, the treatment protocol remains more or less the same. We are using remdesivir extensively because, as per our experience, it works well. We have continued with using steroids and remdesivir and low-molecular-weight heparin. The only thing is about restarting the use of tocilizumab because we had used it early in the epidemic and then there was data to show that it doesn't work. Now we have a couple of trials that show that in a certain subset of patients, one can use it. For the past two or three weeks we have started using tocilizumab in some patients again. That's the only difference.

Dr Mishra, you did a study where you showed that 54% of the sample of people studied in Hyderabad had achieved seroprevalence or immunity or antibodies. How do you see the test and the results of the test in the context of rising numbers? Does the seropositivity still hold the same way it did in a city like Hyderabad?

RM: Whatever tests are being done in Hyderabad, there is not much of an increase in the number of cases. In fact, if you compare with any major big city, they are certainly all 50-plus seropositivity. In previous days, places which have done better, like Kerala, they could control very easily, so that means most of the population was vulnerable because they have not seen infections in the first round. This time you see the infection is more, first it came as a wave in Kerala, but now they have managed to control that. But even in Maharashtra and bigger cities, I think the cases are more because there is a lot of inflow and outflow of people. But it is also going to smaller places where there is a more vulnerable population, vulnerable in the sense that those who hadn't gotten the infection the first time. So the immunity still holds.

I was a little concerned to see that some re-infection cases have started to come, and it will be very important to follow those cases very closely--if these re-infections were in any way related to one of the variants, because that is the one major concern. Actually, I'm not worried about anything else. I don't think these new variants are more infectious. I still feel that behaviour is largely responsible. It is not one or two things, we have changed many things--we have elections, we opened shops, schools, restaurants, cinema halls and local transport and people have become more and more bold that it is over and that vaccines have come, whether they are vaccinated or not.

All of these things, I think, have contributed to this gradual pickup and after that we reached a critical number. But if there is a reinfection that needs to be addressed. That is a major concern, because if the virus is able to reinfect and ignore the earlier immunity, then the vaccine will have to be looked at in a very different context.

You are saying that, if we go by the seroprevalence data, which say that half the population of many cities, maybe many parts of the country, already has antibodies. Would that therefore suggest that the numbers that we are seeing today may hit some kind of a wall after a point?

RM: Yes, that will certainly happen. It is unlikely that this peak will be as high as it was in the first time, in the national context. Hopefully, unless they say that the virus has become resistant to the previous immunity acquired. People who have had the first dose and even the second dose [of a vaccine] may get infected because vaccines at the best have an efficacy of 80%-90%. So one or two out of 10 will get infected and when you're talking about thousands of such numbers, that is not such a big concern. And these vaccines are also not known to prevent infection but they will reduce the symptoms, and mortality will be more or less in control, hopefully.

But I think the existing seropositivity and availability of the vaccine may tilt the balance in our favour. If a large number of people take the vaccine very quickly--the government is now slowly opening up vaccination [to more age groups and in the private sector]--and most importantly, we keep using masks and social distancing as much as possible, this peak might not be as problematic as it was earlier. I really hope that we will be able to avoid a huge lockdown like before [as] that will be a bigger killer.

Dr Singhal, can you tell us a little more about the reinfections that you have seen, more clinical insight into what seems to have happened, and what has been the outcome?

TS: As of now, I can only say that there have only been two reinfections in my clinical practice, one is a 13-year-old girl who had COVID in December, and then she was fine, but she did not develop antibodies when the father got her tested. Now she has come back with fever and respiratory tract infection and her COVID PCR is positive with a low CT [cycle threshold] value that tells us that this is probably early disease. There is another case who had COVID somewhere in July, a 45-year-old male, and now he has come back with a reinfection. The severity of the disease continues to be mild in both these patients, so that's not an issue. We would be more worried if both these reinfections had severe disease. As Dr Mishra said, post two doses of the vaccine we will see breakthrough infections, because the efficacy is not there. We would be more worried if after vaccination, people start getting severe disease. As of now, that has not happened. This tells us that even if there is some mutation of [the COVID-19 virus], the vaccines are likely to protect and people should go ahead.

The common question that people start asking now is, do the vaccines protect against whatever variants are circulating, We keep counselling them [that], yes, they protect and there is nothing better to offer right now. We believe that even though they may not protect against mild infections, they do protect against severe disease. One thing I just want to say is we have had infections in healthcare workers. They also tend to become lax with precautions. But we saw a peak in May and June and now we are seeing an increase again so I am a little worried. I do feel that, at least in Maharashtra, we have a more infectious variant circulating and I think the rest of the country will follow. Even when we had the first COVID wave, we found states like Maharashtra, in cities like Mumbai, were affected first and then it percolated to other states. We don't know what is going to happen in the next few weeks.

You talked about healthcare workers getting infected. The reasons I am assuming are the same--that they are lax, they are not wearing their masks as often. The other corollary question is do you think they are getting infected inside the hospitals or is it outside?

TS: Most of them are getting infected outside. None of the people working in the COVID unit are. The only thing that I want to say is that people started becoming lax about masks not just now. We have been observing people's behaviour from December, people have become very lax with these things. But the surge has come now so either once it reaches a critical stage it starts becoming obvious. But the lack of precautions started happening about three to four months ago.

Dr Mishra, what else are you looking at now, at the laboratory level or, the studies that you are doing? How are you trying to understand this virus better and where could that lead us?

RM: What we are trying to do is [find out] if there is a variant--new or existing--which is spreading faster and occupying a larger proportion of the infected cases. We are doing [this] at a national level [for which], we have set up a network of 10 labs all over the country. The other thing that we are doing is that we are culturing this double mutant in the lab to see if it is resistant to the serum from the vaccinated people or the people who have recovered from previous infection. This will tell us whether we have to worry about any vaccine problem that may come up with this.

The main thing, as I said, is to collect samples from all geographical locations, particularly from the places where the superspreading events are seen, to see if a new or more dangerous variant is now emerging. We are in close contact, and always looking for cooperation from hospitals to report and share samples of the reinfections, or if there are infections with severe symptoms, so that we can go back to the genome and see if there is a variant that is causing this or, if it is patient-specific. These are the things which, if we do carefully, and as Dr Singhal mentioned, if you wear masks properly it doesn't matter how dangerous or infectious the variant is. All the health workers wear masks and treat people, so if we do that, we can actually win this race this time with less trouble, particularly because now the vaccine is there; so that will be a major factor. If we tighten up a little bit, we can come out of this without any major lockdowns, which [a lockdown] I hope will not happen and the wave will come under control soon.

You seem to be very concerned about a potential lockdown. Is that because you feel it will only hold back economic activity and COVID-19 will sort of explode once you lift the lockdown, just like it happened the last time?

RM: Lockdown causes so much social trouble. We saw last time what happened during the lockdown, particularly to poor people. It is very heartbreaking and it causes much more damage to society than the virus did. And it causes an economical loss. The people who suffer are the ones who are helpless and are at the lower strata of the society. That is why this is something that we should worry about.

Dr Singhal, as you look ahead, how well-prepared are you, mentally and physically, as a team, to continue this battle? It has been a year now, where do you expect help?

TS: We are better prepared than before because we now have experience on our side, but mentally, I think everybody is tired--healthcare workers, administrators, nurses. I hope we see an end to this fast because eventually, the system does give way because everybody is tired. Everybody was feeling okay that now this is over, let's start looking at new things. Now it is again back to square one. We are all better prepared, but tired at the same time. But the vaccine makes things better. This time there is some light at the end of the tunnel, which is the vaccine, and we really have to ramp up vaccination very fast; we have to do it at a war-footing.

Dr Mishra, any numbers that you have run on vaccines? At what point will we maybe be a little safer?

RM: It is not my expertise but if it was possible, we should be vaccinating maybe half a crore or a crore [5-10 million] a day. In this way, in two or three months, we can reach a good number and with prevailing sero-positivity, we may get closer to herd immunity. We should put the focus on promoting people to get the vaccine and supply is not a problem, so hopefully we will reach there.

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