40% Of People Have No Symptoms, They May Be Key To Ending Covid: Report

Agencies
August 9, 2020

When researcher Monica Gandhi began digging deeper into outbreaks of the novel coronavirus, she was struck by the extraordinarily high number of infected people who had no symptoms.

A Boston homeless shelter had 147 infected residents, but 88% had no symptoms even though they shared their living space. A Tyson Foods poultry plant in Springdale, Ark., had 481 infections, and 95% were asymptomatic.

Prisons in Arkansas, North Carolina, Ohio and Virginia counted 3,277 infected people, but 96% were asymptomatic.

During its seven-month global rampage, the coronavirus has claimed more than 700,000 lives. But Gandhi began to think the bigger mystery might be why it has left so many more practically unscathed.

What was it about these asymptomatic people, who lived or worked so closely to others who fell severely ill, she wondered, that protected them? Did the "dose" of their viral exposure make a difference? Was it genetics? Or might some people already have partial resistance to the virus, contrary to our initial understanding?

Efforts to understand the diversity in the illness are finally beginning to yield results, raising hope that the knowledge will help accelerate development of vaccines and therapies - or possibly even create new pathways toward herd immunity in which enough of the population develops a mild version of the virus that they block further spread and the pandemic ends.

"A high rate of asymptomatic infection is a good thing," said Gandhi, an infectious-disease specialist at the University of California at San Francisco. "It's a good thing for the individual and a good thing for society."

The coronavirus has left numerous clues - the uneven transmission in different parts of the world, the mostly mild impact on children. Perhaps most tantalizing is the unusually large proportion of infected people with mild symptoms or none at all. The Centers for Disease Control and Prevention last month estimated that rate at about 40%.

Those clues have sent scientists off in different directions: Some are looking into the role of the receptor cells, which the virus uses to infiltrate the body, to better understand the role that age and genetics might play. Others are delving into masks and whether they may filter just enough of the virus so those wearing them had mild cases or no symptoms at all.

The theory that has generated the most excitement in recent weeks is that some people walking among us might already have partial immunity.

When SARS-CoV-2, the technical name of the coronavirus that causes the disease covid-19, was first identified on Dec. 31, 2019, public health officials deemed it a "novel" virus because it was the first time it had been seen in humans who presumably had no immunity from it whatsoever. There's now some very early, tentative evidence suggesting that assumption might have been wrong.

One mind-blowing hypothesis - bolstered by a flurry of recent studies - is that a segment of the world's population may have partial protection thanks to "memory" T cells, the part of our immune system trained to recognize specific invaders. 

This could originate from cross-protection derived from standard childhood vaccinations. Or, as a paper published Tuesday in Science suggested, it could trace back to previous encounters with other coronaviruses, such as those that cause the common cold.

"This might potentially explain why some people seem to fend off the virus and may be less susceptible to becoming severely ill," National Institutes of Health Director Francis Collins remarked in a blog post this past week.

On a population level, such findings, if validated, could be far-reaching.

Hans-Gustaf Ljunggren, a researcher at Sweden's Karolinska Institute, and others have suggested that public immunity to the coronavirus could be significantly higher than what has been suggested by studies. In communities in Barcelona, Boston, Wuhan and other major cities, the proportion of people estimated to have antibodies and therefore presumably be immune has mostly been in the single digits. But if others had partial protection from T cells, that would raise a community's immunity level much higher.

This, Ljunggren said, would be "very good news from a public health perspective."

Some experts have gone so far as to speculate about whether some surprising recent trends in the epidemiology of the coronavirus - the drop in infection rates in Sweden where there have been no widespread lockdowns or mask requirements, or the high rates of infection in Mumbai's poor areas but little serious disease - might be due to preexisting immunity.

Others say it's far too early to draw such conclusions. Anthony Fauci, the United States' top infectious-disease expert, said in an interview that while these ideas are being intensely studied, such theories are premature. He said at least some partial preexisting immunity in some individuals seems a possibility.

And he said the amount of virus someone is exposed to - called the inoculum - "is almost certainly an important and likely factor" based on what we know about other viruses.

But Fauci cautioned that there are multiple likely reasons - including youth and general health - that determine whether a particular individual shrugs off the disease or dies of it. That reinforces the need, in his view, for continued vigilance in social distancing, masking and other precautions.

"There are so many other unknown factors that maybe determine why someone gets an asymptomatic infection," Fauci said. "It's a very difficult problem to pinpoint one thing."

- - -

News headlines have touted the idea based on blood tests that 20% of some New York communities might be immune, 7.3% in Stockholm, 7.1% in Barcelona. Those numbers come from looking at antibodies in people's blood that typically develop after they are exposed to a virus. But scientists believe another part of our immune system - T cells, a type of white blood cell that orchestrates the entire immune system - could be even more important in fighting against the coronavirus.

Recent studies have suggested that antibodies from the coronavirus seem to stick around for two to three months in some people. While work on T cells and the coronavirus is only getting started - testing T cells is much more laborious than antibody testing - previous research has shown that, in general, T cells tend to last years longer.

One of the first peer-reviewed studies on the coronavirus and T cells was published in mid-May in the journal Cell by Alessandro Sette, Shane Crotty and others at the La Jolla Institute for Immunology near San Diego.

The group was researching blood from people who were recovering from coronavirus infections and wanted to compare that to samples from uninfected controls who were donors to a blood bank from 2015 to 2018. The researchers were floored to find that in 40% to 60% of the old samples, the T cells seemed to recognize SARS-CoV-2.

"The virus didn't even exist back then, so to have this immune response was remarkable," Sette said.

Research teams from five other locations reported similar findings. In a study from the Netherlands, T cells reacted to the virus in 20% of the samples. In Germany, 34%. In Singapore, 50%.

The different teams hypothesized this could be due to previous exposure to similar pathogens. Perhaps fortuitously, SARS-CoV-2 is part of a large family of viruses. Two of them - SARS and MERS - are deadly and led to relatively brief and contained outbreaks. Four other coronavirus variants, which cause the common cold, circulate widely each year but typically result in only mild symptoms. Sette calls them the "less-evil cousins of SARS-CoV-2."

This week, Sette and others from the team reported new research in Science providing evidence the T cell responses may derive in part from memory of "common cold" coronaviruses.

"The immune system is basically a memory machine," he said. "It remembers and fights back stronger."

The researchers noted in their paper that the strongest reaction they saw was against the spike proteins that the virus uses to gain access to cells - suggesting that fewer viral copies get past these defenses.

"The current model assumes you are either protected or you are not - that it's a yes or no thing," Sette added. "But if some people have some level of preexisting immunity, that may suggest it's not a switch but more continuous."

- - -

More than 2,300 miles away, at the Mayo Clinic in Cleveland, Andrew Badley was zeroing in the possible protective effects of vaccines.

Teaming up with data experts from Nference, a company that manages their clinical data, he and other scientists looked at records from 137,037 patients treated at the health system to look for relationships between vaccinations and coronavirus infection.

They knew that the vaccine for smallpox, for example, had been shown to protect against measles and whooping cough. Today, a number of existing vaccines are being studied to see whether any might offer cross-protection against SARS-CoV-2.

When SARS-CoV-2, the technical name of the coronavirus that causes the disease covid-19, was first identified on Dec. 31, 2019

The results were intriguing: Seven types of vaccines given one, two or five years in the past were associated with having a lower rate of infection with the new coronavirus. Two vaccines in particular seemed to show stronger links: People who got a pneumonia vaccine in the recent past appeared to have a 28% reduction in coronavirus risk. Those who got polio vaccines had a 43% reduction in risk.

Venky Soundararajan, chief scientific officer of Nference, remembers when he first saw how large the reduction appeared to be, he immediately picked up his phone and called Badley: "I said, 'Is this even possible?'"

The team looked at dozens of other possible explanations for the difference. It adjusted for geographic incidence of the coronavirus, demographics, comorbidities, even whether people had had mammograms or colonoscopies, under the assumption that people who got preventive care might be more apt to social distance. But the risk reduction still remained large.

"This surprised us completely," Soundararajan recalled. "Going in we didn't expect anything or maybe one or two vaccines showing modest levels of protection."

The study is only observational and cannot show a causal link by design, but Mayo researchers are looking at a way to quantify the activity of these vaccines on the coronavirus to serve as a benchmark to the new vaccines being created by companies such as Moderna. If existing vaccines appear as protective as new ones under development, he said, they could change the world's whole vaccine strategy.

- - -

Meanwhile, at NIH headquarters in Bethesda, Md., Alkis Togias has been laser-focused on one group of the mildly affected: children. He wondered whether it might have something to do with the receptor known as ACE2, through which the virus hitchhikes into the body.

In healthy people, the ACE2 receptors perform the important function of keeping blood pressure stable. The novel coronavirus latches itself to ACE2, where it replicates. Pharmaceutical companies are trying to figure out how to minimize the receptors or to trick the virus into attaching itself to a drug so it does not replicate and travel throughout the body.

Was it possible, Togias asked, that children naturally expressed the receptor in a way that makes them less vulnerable to infection?

He said recent papers have produced counterintuitive findings about one subgroup of children - those with a lot of allergies and asthma. The ACE2 receptors in those children were diminished, and when they were exposed to an allergen such as cat hair, the receptors were further reduced. Those findings, combined with data from hospitals showing that asthma did not seem to be a risk factor for the respiratory virus, as expected, have intrigued researchers.

"We are thinking allergic reactions may protect you by down-regulating the receptor," he said. "It's only a theory of course."

Togias, who is in charge of airway biology for the National Institute of Allergy and Infectious Diseases, is looking at how those receptors seem to be expressed differently as people age, as part of a study of 2,000 U.S. families. By comparing those differences and immune responses within families, they hope to be able to better understand the receptors' role.

Separately, a number of genetic studies show variations in genes associated with ACE2 with people from certain geographic areas, such as Italy and parts of Asia, having distinct mutations. No one knows what significance, if any, these differences have on infection, but it's an active area of discussion in the scientific community.

- - -

Before the pandemic, Gandhi, the University of California researcher, specialized in HIV. But like other infectious-disease experts these days, she has spent many of her waking hours thinking about the coronavirus. And in scrutinizing the data on outbreaks one day, she noticed what might be a pattern: People were wearing masks in the settings with the highest percentage of asymptomatic cases.

The numbers on two cruise ships were especially striking. In the Diamond Princess, where masks weren't used and the virus was likely to have roamed free, 47% of those tested were asymptomatic. But in the Antarctic-bound Argentine cruise ship, where an outbreak hit in mid-March and surgical masks were given to all passengers and N95 masks to the crew, 81% were asymptomatic.

Similarly high rates of asymptomatic infection were documented at a pediatric dialysis unit in Indiana, a seafood plant in Oregon and a hair salon in Missouri, all of which used masks. Gandhi was also intrigued by countries such as Singapore, Vietnam and the Czech Republic that had population-level masking.

"They got cases," she noted, "but fewer deaths."

The scientific literature on viral dose goes back to around 1938 when scientists began to find evidence that being exposed to one copy of a virus is more easily overcome than being exposed to a billion copies. Researchers refer to the infectious dose as ID50 - or the dose at which 50% of the population would become infected.

While scientists do not know what that level might be for the coronavirus (it would be unethical to expose humans in this way), previous work on other nonlethal viruses showed that people tend to get less sick with lower doses and more sick with higher doses. A study published in late May involving hamsters, masks and SARS-CoV-2 found that those given coverings had milder cases than those who did not get them.

In an article published this month in the Journal of General Internal Medicine, Gandhi noted that in some outbreaks early in the pandemic in which most people did not wear masks, 15% of the infected were asymptomatic. But later on, when people began wearing masks, the rate of asymptomatic people was 40% to 45%.

She said the evidence points to masks not just protecting others - as U.S. health officials emphasize - but protecting the wearer as well. Gandhi makes the controversial argument that while people mostly have talked about asymptomatic infections as terrifying due to how people can spread the virus unwittingly, it could end up being a good thing.

"It is an intriguing hypothesis that asymptomatic infection triggering immunity may lead us to get more population-level immunity," Gandhi said. "That itself will limit spread."

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News Network
July 17,2020

Lukung, Jul 17: Union Defence Minister Rajnath Singh on Friday assured that not an inch of our land can be taken by any power in the world while he interacted with the Indian Army and ITBP personnel at Lukung.

Referring to the India-China border standoff, he said, "Talks are underway to resolve the border dispute but to what extent it can be resolved I cannot guarantee. I can assure you, not one inch of our land can be taken by any power in the world."

Emphasising on finding a diplomatic solution to the standoff, he further said, "If a solution can be found by talks, there is nothing better."
"Recently what happened between troops of India and China at PP14, how some of our personnel sacrificed their lives protecting our border. I am happy to meet you all but also saddened because of their loss. I pay my tributes to them," he added.

Singh interacted with the Army and Paramilitary troops here along with Chief of Defence Staff General Bipin Rawat and Army Chief General MM Naravane.

Earlier today, the Defence Minister witnessed para dropping and scoping weapons here. He also inspected a Pika machine gun.

Indian Army T-90 tanks and BMP infantry combat vehicles carried out the exercise at Stakna, Leh in presence of Singh, Chief of Defence Staff and Army Chief.

Defence Minister is on a two-day visit to Ladakh and Jammu and Kashmir. He will take stock of the situation at both the Line of Actual Control (LAC) and the Line of Control (LOC).

While Pakistan constantly violates ceasefire from across the LoC, China has continued to intrude into Indian territory in Ladakh region in recent past, escalating tensions between India and its eastern neighbour.

On June 15, twenty Indian soldiers laid out their lives during combat with Chinese forces in Galwan valley, leading to tensions between both nations. Chinese soldiers subsequently started moving back following dialogues between two countries through the military level and diplomatic level.

Singh was accompanied by the Chief of Defence Staff General Bipin Rawat and Army Chief General MM Naravane.

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News Network
March 9,2020

New Delhi, Mar 9: A war of words broke out between the BJP and the Congress on Sunday over the Yes Bank crisis with the ruling party seeking to link it with the Gandhi family, while the opposition wondered if the prime minister and finance minister were "complicit" as the bank's loan book grew manifold.

Posting on Twitter a clip of a news channel report that Rana Kapoor, the arrested Yes Bank founder, had bought a painting from Congress leader Priyanka Gandhi Vadra, BJP's information and technology wing in-charge Amit Malviya alleged that every financial crime in India has "deep links" with the Gandhis.

The Congress dismissed the charge "fake" and called it a "diversionary" tactic.

It said Priyanka Gandhi had sold an M F Hussain painting of her father Rajiv Gandhi to Kapoor for Rs 2 crore, and the entire amount was disclosed in her income tax return of 2010.

Malviya tweeted, "Every financial crime in India has deep link with the Gandhis. Mallya used to send flight upgrade tickets to Sonia Gandhi. Had access to MMS (Manmohan Singh) and PC (P Chidambaram). Is absconding. Rahul inaugurated Nirav Modi’s bridal jewellery collection, he defaulted. Rana bought Priyanka Vadra’s paintings."

Congress' chief spokesperson Randeep Surjewala asked how does an M F Hussain painting of Rajiv Gandhi sold 10 years ago by Priyanka Gandhi to Yes Bank owner Rana Kapoor and disclosed in her tax returns connect with unprecedented giving of loans of Rs 2,00,000 crore in five years of the Modi government.

"More so, when (Kapoor's) proximity to BJP leaders is well known," he said.

Rubbishing the BJP's allegation, Congress spokesperson Abhishek Manu Singhvi at a press conference said it was a "diversionary" tactic by the government.

He noted that the bank's loan book rose from Rs 55,633 crore in March 2014, the year Narendra Modi became prime minister, to Rs 2,41,499 crore in March 2019.

"Why did the loan book rise by 100 per cent in two years after demonetisation i.e from Rs 98,210 cr in March 2016 to Rs 2,03,534 ar in March 2018? Were PM and FM sleeping, ignorant or complicit?" he asked.

The entire amount Priyanka Gandhi had received was in cheque and was fully disclosed in the income tax return, Singhvi said.

Surjewala, taking to Twitter, said instead of diverting from the real issue of people's money sinking into a bad bank, should not the government answer questions like how did loans given by Yes Bank rise from Rs 55,633 crore in March 2014 to Rs 2,41,499 crore in March 2019, an increase of almost Rs 2,00,000 crore in fiver years of the Modi government.

Why did the loans given by Yes Bank rise by a whopping 100 per cent in just two years after demonetisation, he asked.

Surjewala also questioned why did the prime minister address a conference sponsored by Yes Bank on March 6 despite the RBI moratorium.

"Why did the Haryana BJP government deposit over Rs 1,000 crore in Yes Bank a month ago, knowing that it was sinking? Is this figure Rs 3,000 cr? Did Fadnavis government in Maharashtra make similar deposits?" Surjewala asked.

"Of course, the government's media proxies won't dare to ask these questions. But the nation wants to know!" he said in a series of tweets.

Kapoor, 62, was arrested by the Enforcement Directorate in Mumbai after charges of alleged financial irregularities and mismanagement in the bank's operations surfaced and the RBI and Union government initiated action to control its affairs.

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News Network
June 29,2020

Karachi, Jun 29: Four heavily-armed militants attacked the busy Pakistan Stock Exchange on Monday morning, killing four security guards and a police sub-inspector before being shot dead in an exchange of fire, media reports said.

The unidentified militants opened indiscriminate fire and lobbed hand grenades at the main gate of the building as they tried to storm it, Geo News reported.

Police said that all the terrorists have been killed while five persons injured in the attack.

Four security guards and a police sub-inspector were also killed in the attack.

"An unfortunate incident took place at the Pakistan Stock Exchange. They made their way from our parking area and opened fire on everyone," said Abid Ali Habib, Director of Pakistan Stock Exchange.

The firing by militants caused panic among the people in the building.

Sindh province Governor Imran Ismail condemned the incident.

"Strongly condemn the attack on PSX aimed at tarnishing our relentless war on terror. Have instructed the IG & security agencies to ensure that the perpetrators are caught alive & their handlers are accorded exemplary punishments. We shall protect Sindh at all costs," he said on Twitter.

Police and rangers have arrived on the spot and surrounded the area.

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