The Vaccine Exit

The Real Lesson of India’s Second Covid Wave

The Battle of Paraguay

The latest battle between India and China is being fought, not in the Himalayan snows, but in the small South American republic of Paraguay.

Paraguay has been badly hit by the pandemic though its Covid-19 mortality rate is lower than that of most Latin American countries. In recent months the situation has become critical, with 4,000 of Paraguay’s 6,000 deaths occurring in 2021.

Non-emergency surgeries were suspended and the healthcare system in Paraguay was on the brink of collapse by March. The country was rocked by protests against the government’s mishandling of the coronavirus crisis and the opposition attempted to impeach the President.

Paraguay was desperate for vaccines. At this stage it was approached by “intermediaries and other private figures” who claimed that they could provide a sufficient quantity of Chinese Covid-19 vaccines to Paraguay if it severed diplomatic ties with Taiwan. (Paraguay is one of the 15 remaining countries that recognize Taiwan, considered a breakaway province of China by the Chinese government. ) Joe Biden, the President of the United States reacted sharply asking Paraguay to work with Taiwan to overcome the global pandemic.

Taiwan had by end of 2020 ordered 20 million vaccine doses. It also plans to develop significant indigenous vaccine manufacturing capacity in the coming months. However in March it had just started its domestic vaccination program with 117,000 shots of the Oxford-AstraZenaca vaccine received from a South Korean factory. It was in no position to provide vaccines to Paraguay or anyone else. But it still promised to help.

Paraguay asked for and received from India 100,000 doses of India’s indigenously developed Covid-19 vaccine, Covaxin, on Monday 30th March. Taiwan seems to have been the intermediary though we do not know the details of backroom deal making.

Paraguay’s woes were far from over. Not only did it need more vaccine. It couldn’t even begin using the 100,000 Covaxin doses that it had. The reason was that Paraguay does not have its own regulatory authority with power to approve vaccines and follows Brazil and Mexico’s lead. Covaxin’s Phase 3 clinical trials are not over yet, though interim results have shown an encouraging efficacy of 81% . The vaccine had been authorized for emergency use by India, Iran, Mauritius, Nepal and Zimbabwe when it was shipped to Paraguay. However, the Brazilian regulator had been less than impressed by its inspection of the manufacturing facilities of Bharat Biotech — the manufacturer of Covaxin- and refused to certify the vaccine claiming that it does not meet its manufacturing standards, leaving Paraguay in limbo. Fortunately Mexico has recently authorized the use of Covaxin and Paraguay should soon follow suit.

The Vaccine Exit

All vaccines significantly reduce the risk of symptomatic Covid-19 infection and severe disease. Moreover, studies in the UK and Israel provide evidence — though not yet conclusive proof-that vaccinated persons are not only at lower risk of contracting the disease but also of spreading it. Herd immunity via vaccines therefore remains humanity’s best hope for a path out of the pandemic.

The simplest model of an epidemic is provided by the equation

R = N x p x (1-f), where R is the average number of persons an infected person infects in turn;

N is the average number of persons who come into contact with an infected person while she is infectious;

p is the probability of the virus being transmitted during a contact;

f is the fraction of the population immune to the infection.

The epidemic equation governs the trajectory of the vaccine exit.

Look at the chart. The horizontal axis shows the cumulative number of vaccine doses administered per 100 population. (The number of doses administered may be more than 100 since most common Covid-19 vaccines require two doses.) A county moves rightward along this axis as it vaccinates more and more people. The vertical axis shows the number of daily new cases relative to the population (shown in logarithmic scale).

An idealized Vaccine Exit Trajectory is marked in yellow. As more and more people are vaccinated f increases in the epidemic equation. Consequently R decreases. As long as R remains above 1 the number of daily new cases continues to rise but once R goes below 1 it falls. Eventually the country moves to the bottom right of the chart and the epidemic dies down.

Look at some countries in the right half of the chart which have been vaccinating aggressively. Having administered about 120 vaccine doses per 100 persons Israel has seen the number of new cases per day go down from a peak of nearly a 1,000 per million to15 per million in a little over 3 months. Deaths have fallen equally dramatically. There is little doubt that this is due to the vaccine as the country has eased restrictions in lockstep with vaccination. United Kingdom’s story is quite similar.

Of course many factors complicate a country’s vaccine exit trajectory. Why did Chile’s curve take so much time to bend in spite of an aggressive vaccine rollout? This could be because of a variety of reasons. N - the average number of contacts of an infected person in the epidemic equation, -— may have increased because Chileans opened up travel too quickly, offsetting the decrease in f. The infectivity p in the equation might also have gone up because the “Brazilian variant” of the virus is spreading in Chile.

The difference between the speed of decline in Israel and Chile could also be partly due to vaccines used in these countries, though the evidence is tentative at this point. The Israelis are primarily relying on the Pfizer-Biontech vaccine. The Israeli study suggests that the Pfizer vaccine is 89.4% effective at preventing infections. The backbone of the Chilean vaccination program, on the other hand, is the CoronaVac vaccine manufactured by the Chinese company Sinovac. A study in Chile suggests that the effectiveness of Coronavac at preventing infection is 56.5% two weeks after a second dose but only 3% after the first dose. Chile may simply need to vaccinate more people to achieve herd immunity. (Caveat: these studies with different contexts and protocols cannot be used for head-to-head comparison of the vaccines.)

So can we hope that all countries will eventually take the vaccine exit to the safe haven at the bottom right of the chart?

But the vaccine exit is littered with traps and pitfalls. India provides a prime cautionary example.

India’s Second Wave

The Oxford-Astrazenaca vaccine and the Serum Institute of India (SII) — the largest vaccine manufacturer in India and the world- were expected to play a big role in the world’s vaccine exit. SII planned to manufacture more than 1 billion doses of the Oxford-Astrazenaca Covid-19 vaccine this year, under the brand name of Covishield. The Serum Institute exported about 50% of the first 95 million doses it manufactured to 51 countries, garnering praise for Indian exceptionalism from some who contrasted India’s altruistic behavior with the selfishness of vaccine hoarding Western nations.

But then the second coronavirus wave smashed into India with much greater force than the first.

In a blog published on 14 February, I had writtenThe hygiene hypothesis and belief in herd immunity are complementary. They suggest that a large part of the Indian population is protected against Covid-19 because of immunity — either innate or acquired through prior infection. Both have gained considerable traction in India and could lull Indians into a sense of complacency. Unfortunately that could have fatal consequences.

Unfortunately Indian citizens & governments were indeed lulled into letting down their guard and the results have been tragic. Since my blog was published the number of daily new Covid-19 cases and deaths has risen more than thirty-fold in India.

And these figures are surely gross under-estimates. Bhramar Mukherjee, Professor of Biostatistics and Epidemiology at the University of Michigan, estimates the number of undetected cases in India to be between 10 and 20 times the number of detected ones. Deaths are being under-counted too. Long queues are building up at crematoriums. Hospitals are running out of beds, ventilators and even oxygen. India is scrambling to import medical oxygen and medical devices from Singapore, Germany and the USA.

The Indian Health Minister blamed “negligence towards covid-19 appropriate behavior” for the surge. There is no doubt that he has a point. Pandemic fatigue had become wide spread across India by January and many people — believing that the worst was behind them- had stopped wearing masks and practicing social distancing in public spaces.

It is however unfair to blame only the citizens. Central and state governments let down their guard too and permitted huge public gatherings.

During election campaigns in several Indian states, senior Indian ministers addressed rallies where thousands crowded together, mostly without masks. Mohana Basu’s analysis shows that in West Bengal, where the election was held in multiple phases, in most districts Covid-19 cases shot up within a couple of weeks of the most intense phase of the election campaign.

Even more ill-advised was the decision of the Uttarakhand state government to let the once-in-twelve-years mega religious congregation, known as the Kumbh Mela, proceed in a pandemic year. More than faith was at stake. The picturesque Himalayan state of Uttarakhand depends largely on tourism and has been grievously hurt by the lockdown last year.

Tens of millions normally attend the Kumbh, and it generates billions of dollars of economic activity. It is no wonder that the government was unwilling to forego all of that.

The Uttarakhand government had apparently relied on its SOPs (Standard Operating Procedures) to keep the Kumbh from becoming a super-spreader event. This was a terrible mistake. These SOPs — such as requiring each pilgrim to provide a negative Covid test report — were drawn up at a time of relatively low disease prevalence and designed for events with perhaps a few hundred or few thousand attendees. It should have been clear that, given the high current Covid-19 prevalence and inevitable false negatives in Covid testing, they would not be enough to save the Kumbh.

Indeed cases in Uttarakhand shot up once the Kumbh commenced on 1 April.

It also spread from Uttarakhand to other parts of India. 10% of the returnees from Kumbh tested positive in the state of Gujarat. The head of a religious order died of Covid-19 during the Kumbh and many other holy men were infected. A worried prime minister asked that the Kumbh be celebrated “symbolically” and several religious orders decided to withdraw. The Kumbh was effectively over though not before enormous harm had been done.

The Health Minister of Assam had said on 4 April that his state was Covid free and no one there needed to wear a mask. It would be hard to find a better example of misplaced complacency. Within 3 weeks the number of new daily cases had increased from 70 to over 2,000 and the state was looking for oxygen from the neighboring Kingdom of Bhutan.

The second wave is spreading much faster than the first and apart from complacency new and more transmissible virus variants seem responsible for the runaway growth.

The infamous “UK variant” (B1.1.7) which is known to be more infectious than the original “wild” variety, has been found in 81% of the samples sent for genome sequencing from the state of Punjab. India’s leading epidemiologists Shaheed Jameel, and Gautam Menon, both consider it very likely that a “double mutant” strain (B.1.617) is driving the caseload growth elsewhere in India though this is not yet definitively established epidemiologically because of insufficient genome sequencing.

Nobody likes to say the l-word in India. While the countrywide lockdown of 2020 had undoubtedly saved lives it had crushed the economy and inflicted great hardship on the poor. However lockdowns across most of India seem inevitable if total collapse of the healthcare system is to be avoided. States such as Delhi, Maharashtra and Karnataka have already entered into lockdowns of varying severity and duration and others will surely follow.

Looking East

With the second wave hitting India hard, demand for vaccines sky-rocketed. Vaccine supply couldn’t keep up pace. The shortfall in supply was also partly due to an extraordinarily short-sighted and selfish ban by the USA on ingredients and materials required for vaccine manufacture. Healthcare professionals to administer the vaccine were also in short supply given the rise in patient numbers. Several vaccination centers had to close down temporarily.

Faced with the crippling shortage India virtually stopped vaccine exports. Without Indian vaccines countries like Jordan and Paraguay, in the top left quadrant of the chart, will find it harder to make their vaccine exit. Paraguay may need to turn to Chinese vaccines after all though their relatively low efficacy and lack of data transparency still fuel concerns.

Many have blamed India for not rolling out its vaccination drive faster and for exporting vaccines while the majority of Indians were not yet inoculated. However, vaccinating the huge Indian population was bound to be a challenging task. India could perhaps have done better but I doubt that it could have vaccinated a significant proportion of the population in time for the second wave. I also think India did the right thing, from both an ethical and practical standpoint, by exporting vaccines while its own caseload was low.

Where India failed spectacularly was in keeping its caseload (and death count) low during the vaccine rollout.

It has been reported that India’s Covid-19 task force did not meet in February and March. If true, this was a serious lapse. India could have slowed the second wave and significantly mitigated its impact by banning large gatherings and isolating affected areas as soon as the surge became manifest in late February - early March.

Other countries must not repeat India’s mistake.

It is worth noting that India’s reported daily per capita caseload is still lower than that of several European countries. This is of course no consolation to India where the current caseload is overwhelming the healthcare system. But even lower caseloads would probably bring down the healthcare system in countries like Myanmar and Nigeria.

And India must not repeat its mistake either.

Arvind Panagariya, professor of Economics at Columbia University and former adviser to the Government of India offers some advice on what India must do to avoid third and subsequent Covid waves. He offers good advice on how India can scale up its vaccine production and administer more vaccines. Yet his central message seems to be that the only way out for India is to increase vaccination speed so that herd immunity is achieved as fast as possible. Individuals must protect themselves as best as they can by wearing masks and staying indoors till this happens.

Professor Panagariya is undoubtedly right in emphasizing the importance of vaccination. However, he is wrong in focusing only on vaccination.

Nobody can predict whether and when a third Covid wave will strike India. With the USA belatedly reversing its ban and Indian government providing additional funding to its vaccine manufacturers production will undoubtedly scale up. India is also importing Sputnik V from Russia and will probably authorize other vaccines. Even so, with less than 2% of the Indian population fully vaccinated at this point herd immunity is not going to be achieved anytime soon. And the herd immunity threshold is itself a shifting target given new variants, breakthrough infections and waning immunity.

So while vaccinations must continue as fast as possible, governments, healthcare providers and citizens must also continue to work together to minimize the loss of lives and burden on the healthcare system using well established public health measures.

Perhaps one of India’s major mistakes was to benchmark itself against the west, rather than the east when it came to Covid control.

East Asian countries have done a remarkably good job of protecting their citizens during the pandemic. (Well, I do stretch geography a bit here to include Australia and New Zealand in East Asia & exclude countries such as Indonesia and the Philippines!)

They haven’t all used the same tactics. Their strategic goals have also not been identical. For example New Zealand has always aimed at total virus eradication. On the other hand, Singapore and South Korea have tried to contain the disease at a low level of incidence.

But these countries do have many things in common. None of them flirted with herd immunity. They all took appropriate and calibrated action whenever caseloads threatened to rise above a fairly low threshold. Messages from the government were clear and consistent (though a little less so in Thailand and Japan). When mistakes were made they were acknowledged and reversed quickly.

And the East Asians did make mistakes — sometimes serious ones. Singapore, for example, was blindsided by a Covid-19 outbreak in the migrant worker dormitories which pro-active testing could have prevented. But it acted fast, and imposed a strict lockdown to isolate the outbreak.

No doubt that caused hardship — especially to the migrant workers — as western media often point out. Still because of this it was possible to keep down the mortality rate among workers by very carefully monitoring their health. Singapore’s low death rate was no fluke. Singapore also provided food and wifi and psychological counseling to affected workers during their long lockdown. The government ensured that workers continued to receive their wages during their period of inactivity. Most importantly, the government paid for Covid care, treatment and rehabilitation expenses of all sick workers and is now vaccinating all workers free of cost.

There was nothing particularly East Asian about the methods used by these countries. They all kept Covid-19 in check using a mix of well established infectious disease control tactics; limiting crowds, masking, testing, contact tracing, quarantine and border controls.

A glance at the chart shows that most East Asian countries crowd into the bottom left quadrant. Their vaccine rollouts have been slow though Singapore is doing better than the rest. Still, the bottom left of the chart is not too bad a place to be. Except for restrictions on travel most East Asians are enjoying a quality of life similar to pre-pandemic level.

In fact 7 out of the 10 best places to be during the pandemic according to Bloomberg’s resilience index are in East Asia.

Of course the East Asians have been victims of their success to some extent. They succeeded in containing Covid-19 transmission so well that most of their populations are still susceptible to the virus. So they require constant vigilance. A breakthrough infection leading to the infection of a fully vaccinated nurse has just led to a hospital cluster in Singapore. This is Singapore’s greatest challenge since the dormitory outbreak.

The East Asians know that they can’t afford to open their borders until they succeed in vaccinating most of their population. This is hard for a trade dependent region but especially so for the city states of Hong Kong and Singapore and tourism dependent economies like Thailand.

So the East Asians are certainly keen on their vaccine exit. While vaccinating their populations they are also building up capacity. Singapore, South Korea and Vietnam are all developing indigenous vaccines to protect themselves from supply chain disruptions. South Korea will also manufacture Novovax and Sputnik-V vaccines under license in addition to Oxford-Astrazenaca. Australia and Thailand are also producing or will soon produce the Oxford-Astrazenaca vaccine under license.

There is one simple, harsh and trite lesson to be learned from India’s second wave. It is a lesson that the pandemic has taught us — again and again. Covid-19 is a hard taskmaster; if we don’t take it very seriously it will make us pay. While vaccines offer a way out of the pandemic negotiating the vaccine exit is tricky. It needs more than just vaccines. All public health measures need to be in place to avoid stumbles.

Disclosure: I am the Director of Smart Consulting Solutions Pte Ltd, incorporated in Singapore and its subsidiary Radix Analytics Pvt Ltd, incorporated in India. I am also a Visiting Faculty Member at the Indian Institute of Management, Udaipur. The opinions expressed in this article are solely mine and not necessarily shared by any company or institution with which I am affiliated.

Prof. Gautam Menon’s Facebook posts are a treasure trove of information regarding Covid-19.

I am especially grateful to my friend Dr. Ashish Kumar Dawn for his help with this article.

I have spent over 30 years in academia and industry exploring how to use mathematical methods to solve real world problems

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