Oct 9, 2020 - What’s The Tech Transformation TCS CEO Rajesh Gopinathan Is Talking About

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What can smallpox teach us about how we’ve managed COVID-19?

- Smallpox killed an estimated 300 million people in the 20th century alone.
- In 1980, smallpox was the first disease to be officially eradicated.
- Lessons from dealing with past pandemics apply to COVID-19.

For many global health decision-makers, COVID-19 has come to symbolize a failure to apply lessons from past experiences with infectious diseases and raised pressing new questions to be addressed ahead of the next pandemic.

I had the honor of being involved in the campaign to eradicate smallpox, a devastating disease whose historical names - pox, speckled monster and red plague - hint more clearly at the pain and suffering it caused hundreds of millions of people over centuries.

After a decades-long fight to prevent transmission and inoculate people the world over, the last known case of Variola major was diagnosed in a three-year-old Bangladeshi girl named Rahima Banu, and the last case of Variola minor in October 1977, in Somalia. The World Health Organization, which estimates the disease killed 300 million people in the 20th century alone, declared in 1980 that it was the first - and so far only - human disease to be eradicated globally.

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Is India's coronavirus death 'paradox' vanishing?

Travel for this story was supported by the Pulitzer Center. Science's COVID-19 reporting is supported by the Heising-Simons Foundation. At a tiny rural hospital about 1 hour's drive northeast of Pune, India, in early April, workers loaded an SUV with coolers, syringes, vials, thermometers, and electronic tablets. They drove 20 minutes to the village of Karandi, slowing to pass caravans of migrant sugarcane cutters in ox carts. They spent more than an hour taking blood samples at a cluster of houses shared by three generations of one family. Later, the team would scour the blood for antibodies that indicate past run-ins with COVID-19. Girish Dayma, who helps oversee this research program run by a satellite of King Edward Memorial (KEM) Hospital in Pune, says the team's surveys show that up to 40% of these villagers have antibodies for SARS-CoV-2. “It was thought that the rural area was not much affected,” Dayma says. “The data are very much important to convince the policymakers that we need interventions in rural areas.” Studies like KEM's are also crucial to determining whether, as some researchers believe, India's horrific death toll is actually lower than expected from the rate of infections. Good data are scarce. Last week, hundreds of Indian researchers appealed to the government to release what it has and collect more. “[O]ur inability to adequately manage the spread of infections has, to a large extent, resulted from epidemiological data not being systematically collected and released in a timely manner,” they wrote. The current surge in COVID-19 cases has humbled those who thought the country had bested the disease. In early February, with cases dropping below 10,000 per day, restrictions were dropped, political leaders staged massive rallies, and masks became rare in many crowded locales. But the devastating surge starting in late March gave the lie to the suggestion that India might be approaching herd immunity; 10,000 cases hit Pune alone the day the KEM team visited Karandi. A few weeks later, India topped 400,000 cases in a single day. Debate has swirled over whether new variants or waning immunity are at work, just how many people have become infected, and—most contentious—how many have died. Official figures suggest that, compared with other countries, India has recorded relatively few deaths given its count of COVID-19 cases. “We have been trying to find explanations for the low number of deaths in India since last year,” says a signatory of the appeal, microbiologist Gagandeep Kang from the Christian Medical College, Vellore. “The ‘Indian paradox’ really is quite puzzling,” says Prabhat Jha, an epidemiologist at the University of Toronto. Explanations include underestimates of deaths, demographic effects, and environmental factors like abundant vitamin D from the Indian climate. But now, with hospitals struggling to find enough oxygen for their COVID-19 patients, crematoria overwhelmed, and media reports of intentional undercounting of deaths to make the current deluge look less dire, the seeming paradox may be disappearing. In India's first wave, which ran from June through November 2020, cases never went above 100,000 per day. Hospitals struggled—the KEM intensive care unit in Pune for a time relied on raincoats instead of proper gowns—but few reached capacity with severely ill patients. Even then, it was hard to nail down the magnitude of infections and death. “We rely on reporting of positive cases, which obviously leaves big gaps because a large percentage of people are asymptomatic, and a lot of people don't have access to testing,” says Soumya Swaminathan, chief scientist at the World Health Organization and a native of India. For mortality, she notes that only 20% of death certificates list a cause. The notion of an Indian paradox surfaced as early as April 2020 and remains largely speculative despite frequent references by the health minister. One convincing study looked at 450,000 people who sought COVID-19 tests between June and the end of 2020 in 12 of the most populous Indian cities, including New Delhi, Mumbai, Pune, Kolkata, and Chennai. Led by Jha, it found that seropositivity over time jumped from about 17.8% to 41.4%, implying a huge increase in cases. Yet even after factoring in 30% underreporting of COVID-19 deaths—the worldwide average—the team calculated about 41 deaths from COVID-19 per 100,000 population, they reported in March on medRxiv. That mortality rate is less than half the corresponding U.S. figure. Other studies, however, suggest the demographics of the outbreak could explain the anomaly. One thorough study looked at reported COVID-19 cases and deaths last spring and summer in two southern Indian states, Andhra Pradesh and Tamil Nadu, that are home to about 10% of the country's population. The researchers reported that older adults—the group at greatest risk of dying—accounted for relatively few of India's infections ( Science , 6 November 2020, p. [691][1]). Only 17.9% of the deaths in the study were in people age 75 or older, compared with 58.1% in that age bracket in the United States. One reason is that India's population skews young. In 2011, the most recent census year, 45% of the population was 19 years or younger, and only 4.8% was 65 or older. And infection rates in the old were unusually low, perhaps because those who survive to old age in India are often wealthier and better able to socially distance, the researchers argue. The results don't mean COVID-19 is any less deadly in India, notes the paper's first author, Ramanan Laxminarayan, an economist and epidemiologist who founded the Center for Disease Dynamics, Economics & Policy in Washington, D.C., and New Delhi. Unsurprisingly, increasing age was accompanied by a steady climb in the COVID-19 death rate, peaking at 16.6% in those 85 and older. “If you have 65% of your population in an age group where mortality rates are extremely low, then obviously, you're going to see an overall case fatality rate that's extremely low,” he says. He calls claims of an Indian paradox “nonsense.” Other factors also help explain India's seemingly low death rates, Laxminarayan says. In the first wave, infections spread disproportionately in the urban poor, many of whom had to show up for work even during lockdowns, he says. Compared with wealthier city dwellers and those in rural villages, the urban poor are younger and have less obesity—characteristics linked with lower likelihood of severe COVID-19. The states where the team worked have reliable death numbers because they started disease surveillance early, the researchers write. But elsewhere in the country, Laxminarayan suspects far more people have died than reported, noting that cases have been vastly underestimated. A study from the Indian Council of Medical Research found antibodies in 7.1% of nearly 29,000 people in 21 of India's 36 states and union territories. Published on 27 January in The Lancet Global Health , the findings imply that when the study finished collecting data in mid-August 2020, India had nearly 75 million cases—about 30 times higher than the case count then. “By that token, is it really unreasonable to think that deaths are underreported by a factor of four or five?” Laxminarayan asks. ![Figure][2] CREDITS: (GRAPHIC) K. FRANKLIN/ SCIENCE ; (DATA) OUR WORLD IN DATA COVID-19 DATA REPOSITORY VIA JOHNS HOPKINS CENTER FOR SYSTEMS SCIENCE AND ENGINEERING; JOHNS HOPKINS CORONAVIRUS RESOURCE CENTER Yet those who believe India's death rate is unusually low point to several factors. One, Jha says, is household structure. As with the family in Karandi, three generations in a home is a norm in many places. India's relatively small older population means young people are the most likely to bring COVID-19 into a household, and they tend to have lower levels of virus and more asymptomatic infections. Jha notes that reports suggest between 70% to 90% of infected people in India don't develop symptoms. As a result, older people tend to be exposed to lower doses of virus, which their immune systems may be more likely to control. Some scientists have suggested genetics might also play a role. Anurag Agrawal, who heads the Council of Scientific & Industrial Research's Institute of Genomics and Integrative Biology, the leading contributor of a consortium that sequences SARS-CoV-2 in India, says genetic and environmental factors might be linked. Indians who live in the United States or the United Kingdom, he says, suffer just as much from severe COVID-19 as other people there. His team has its own “very controversial” theory, which it has yet to publish because the lead author fell ill with COVID-19. Some hotly debated studies have found lower rates of COVID-19 hospitalization in smokers, Agrawal notes. He points out that high COVID-19 death rates tend to occur in countries with the best air quality. His team contends that smokers and the many Indians who live with bad air pollution might overexpress a variation of an enzyme, CY1P1A1, that “detoxifies” the lungs and destroys the virus through a previously described phenomenon, “xenobiotic metabolism.” Jha and others are skeptical. “There's very little association with particulate matter and COVID infection cases or deaths in our analysis,” he says. The mortality pattern may shift during the current surge. This time, the virus appears to be causing serious illness in younger people more frequently and walloping wealthier populations. And Swaminathan notes that unlike in India's first wave, when hospitals never filled to capacity, “People are dying unnecessarily because health systems can't cope.” But Jha says those trends are not dispelling the paradox. Recent data from Maharashtra suggest mortality rates of confirmed cases haven't changed much—deaths have surged catastrophically, but so have cases overall. Only more and better data will resolve whether India is benefiting from a paradox and, if so, whether it will hold. Agrawal, who is in New Delhi, says India is in a wait-and-see mode. “It's just crazy here these days,” he says. If patterns from other countries play out in India, he predicts the wave will begin to die down in mid-May. “Until then, we need to hold on.” [1]: http://www.sciencemag.org/content/370/6517/691 [2]: pending:yes

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