Covid-19 second wave: Can India find a way out of its health nightmare?

Bobby Ghosh: India is suffering the world’s worst Covid-19 crisis. The daily infection rate is more than 300,000; the daily death toll, in excess of 2,000, is very likely an undercount. The health system has broken down, with scarcities in everything from hospital beds to oxygen. The Indian government has restricted vaccine exports and is instead trying to secure supplies from abroad.

You’ve experienced this disaster firsthand as the head of the Trivedi School of Biosciences at the Ashoka University, near New Delhi. Last fall and winter, it looked like India was doing very well in managing its Covid outbreak. Looking back now, what did we miss?

Shahid Jameel, director, Trivedi School of Biosciences, Ashoka University: We were still on a rising curve in August, and it seemed like India would cross the 100,000-per-day mark. The peak came in mid-September, when we were pulling roughly 97,000 cases. But then, suddenly the graph started dropping and for the next five months, the graph kept dropping, dropping.

There were some seroprevalence surveys being done — that’s when you take blood samples from the population at random and look for the presence of antibodies — and it appeared that maybe 20% to 30% of the overall population had been exposed. In large cities, like in Mumbai and Delhi, in the areas that were surveyed, it appeared as though 50% to 60% had been exposed. That blindsided us: We started believing that the figures were representative of the entire city, but they weren’t. Most of the infection that we saw in that time was in very crowded slums.

There were also theories suggesting India’s mortality rate was low; it wasn’t. It was comparable to Pakistan and Bangladesh. In Sri Lanka and Nepal, [the death rate] was much lower than in India. In all of Southeast Asia, everyone was in the same range. But India was comparing itself to the U.S. and Europe, and India’s case fatality rate was half of theirs. That said, mortality data in India is always dubious, because even in the best of times, death registration in the country is rather poor.

So there were multiple factors that led us into falsely believing that we were out of it. As a result, we let our guard down at a time when we should not have. We should have gathered better quality scientific data, which we didn’t.

BG: What led to the recent surge of cases and death?

SJ: In mid-February, our daily caseload was at its lowest, fewer than 11,000 per day. But mutant viruses were already circulating at low levels before then. Sequencing data now tells us that what we’re calling the Double Mutant variant — the technical name is B.1.617 — was already seen in December, but it was very minor and nobody really paid attention to it. That, and the introduction of the U.K. variant (B.1.1.7) into India in January, finally caught up with us and led to the surge that started from about the third week of February.

The variants are far more infectious and move faster. In the first wave, we would see one person in a family getting infected, and if they isolated themselves, the rest of the family was fine. Not so this time. Now, by the time you realize one person has it, the whole family is down.

I’m part of a sequencing consortium — there are 10 labs in all, and we meet every alternate day to exchange notes. There’s a dashboard that tells us what’s happening. So when we look at different parts of the country, we see several variants that are going around.

In Punjab almost 80% the virus circulating is the U.K. variant. And it’s the same is in Haryana, the neighboring state. But in Delhi, we have the U.K. variant and the Double Mutant, both. In Maharashtra, there’s more of the Double Mutant, up from 15% to 20% in February to roughly 35% to 60% now, depending upon where you look.

BG: Could you explain why it is being called the Double Mutant?

SJ: It’s actually a misnomer. This is a mutant virus that has 15 different changes from the original. Six mutations are in the spike protein, and two of those are in a very critical region called the receptor binding motif. This is the region of the spike protein that allows the virus to enter the cell. It is also the region that is targeted by antibodies that neutralize the virus. So, any small changes in this region have the potential to increase the entry of the virus into cells and evade neutralizing antibodies.

Of the two key mutations in the Double Mutant variant, one was first seen in Denmark, in the mink population. That mutation was then found in humans in California. It was responsible for the expansion of the outbreak in Southern California. The second mutation is very similar, but not identical, to one found in the South African variant, which is responsible for partially evading antibodies.

These two mutations came together for the first time, as far as we know, in this Indian variant.

BG: You said the Double Mutant was present last December , but only caught fire in February. Might there be other variants out there, now only in isolated pockets but with the potential to take off in the same way?

SJ: There could be, and that’s why genomic surveillance is so important — to catch minor variants before they explode in the population.

According to World Health Organization recommendations, you should be sequencing about 0.3% of the confirmed cases. India was much below that rate. By December, India was only at 0.05%. But with the establishment of this sequencing consortium of 10 labs, we’ve been sequencing at about 1% since February.

By now, about a million sequences have already been obtained from infected people around the world, and these sequences are publicly available. So, if you find something rare in your country, it’s possible that somebody has seen it somewhere else. These could have developed independently: If a particular part of the virus is subject to mutation and selection pressure in, let’s say, Europe, why wouldn’t that be in India?

Hopefully, if we do things well now, we will be able to prevent a big third wave. We may not be able to prevent a third wave, because that’s how viruses naturally cycle down before they become endemic, but at least we can reduce the magnitude and also extend the period between the waves, by doing some active genomic surveillance.

BG: Anecdotally, it seems to me that more younger people in India seem to be catching the virus now, and also dying from it. Is that consistent with what you are seeing?

SJ: I’ve been hearing that, too. I have an explanation for it. Younger people are more risk-taking, they go out more and if you have a situation where there is a fast-moving, more infectious virus, they will catch it.

Now, I’m not sure whether you can say that the mortality rate is higher in young people. But it’s simply a matter of numbers. If the mortality rate stays the same and five times more people get infected, then five times more people will die.

BG: To what degree have misconceptions about the virus and the vaccines informed public policy?

SJ: India started vaccinating at the right time, because we were at the low point in our daily caseload — that was in the middle of January. Unfortunately, at that time, there was this constant narrative that India had done so well, that India was out of it. It made people careless. Many didn’t seek vaccination, including doctors and healthcare workers, who were the first group to be given the vaccine.

Right around that time, there were reports that the AstraZeneca vaccine was causing blood clots in Europe. That contributed significantly to vaccine hesitancy here. As you know, most of the doses being given in India are of Covishield (the Indian version of the AstraZeneca vaccine, produced by Serum Institute), so that really affected us quite a bit.

By the time people got around to accepting the vaccine, the surge had started.

BG: What’s the biggest challenge now?

SJ: To bring things under control, you want to vaccinate more people on a daily basis than the number of new infections. Remember that a person who gets the first shot today will get the second shot in four to six weeks, and will need two more weeks to develop full immunity. So somebody who starts vaccination today will take two months to develop protective immunity.

This means the vaccination drive has to be sustained over months, many more doses daily than cases. Only then can we reverse the surge.

BG: Is the supply of vaccines sufficient to maintain that pace?

SJ: One of the critical errors we made was in vaccine procurement. In January, the government ordered only 11 million doses [from Serum Institute]. Between Serum Institute and Bharat Biotech, we can currently produce roughly 90-100 million doses in a month. But they also have exports commitments, especially to the WHO’s COVAX program.

Meanwhile, India has begun to accept vaccine registration from anyone aged 18 or older. In total, we’re talking about 800 million people, or 1.6 billion doses. It’s going to be a struggle.

BG: What are the lessons that other countries should learn from the Indian experience?

SJ: Lesson number one: Masks have to be a permanent feature of your attire, at least for the next year, maybe year and a half, two years. There’s too much focus on this variant or that variant, but don’t forget that every variant can be stopped by a good mask.

Second, get vaccinated. Don’t worry about whether the efficacy of the vaccine is 60%, 70% or 90%. Get whatever vaccine is easily available. The third lesson has to do with public policy, with international health policy: The world needs to decentralize vaccine production. It can’t depend on just three or four countries to make vaccines for everyone. In early March, The Economist predicted that by the summer of 2021, India’s Serum Institute would be supplying 50% of the world’s Covid vaccines. People should have been asking: What if India shuts down?

And there really needs to be a different model of funding for some of these things. I am not an economist, but I can see that vaccine equity is a challenge. Some countries have reserved enough to vaccinate five times their population, whereas others can barely manage 20% of their population. But with infectious diseases, if anyone, anywhere, is left unprotected, then no one anywhere is protected.

And the final lesson: Don’t be in a reactive mode, but plan for the future. That means addressing the core reasons why this virus jumped into humans and spread. And the answer lies in what we are doing to our environment. All of these viruses are coming from wild animals. We are destroying animal habitats and bringing them closer and closer to human habitats, and that’s why the spillover is taking place more frequently. In the entire 20th century, we had three pandemics — flus in 1918, 1957 and 1968. In just the first two decades of the 21st century, we’ve had two — the 2009 swine flu and now Covid-19 — and a few near misses.

BG: Given the situation in India now, would you support the idea of another lockdown?

SJ: Not a nationwide lockdown, but certainly regional lockdowns, citywide lockdowns, local lockdowns. That’s the only way to break transmission. And maybe short lockdowns, so that they don’t affect livelihoods.

And there has to be better communication. Unfortunately, the messaging over the past few weeks has been very, very bad. On the one hand, the Delhi High Court says you must be wearing a mask when you’re in a car, even by yourself. On the other, hundreds of thousands of people are gathering in election rallies without masks. There are people at the Kumbh Mela [a Hindu festival that attracts millions of devotees] without masks. People will not comply if every day they see guidelines being flouted by their leaders, those they look up to.

BG: How long do you think it will take for the virus to become endemic, to a point where we can take preventative jabs annually, as we do for the flu?

SJ: It’s really hard to say. It depends on a few things: how much vaccine coverage we can get and how quickly; how long protection lasts; and what proportion of the population gets infected; and what kind of mutant viruses develop. Remember, the virus is only a year old. Long-term studies haven’t really been done yet. We don’t have the answers, but the next few years are going to be critical.