How Will the COVID Pills Change the Pandemic?

In March, 2020, researchers at Emory University published a paper about a molecule called NHC/EIDD-2801. At the time, there were no treatments available for the coronavirus. But NHC/EIDD-2801, the researchers wrote, possessed “potency against multiple coronaviruses,” and could become “an effective antiviral against SARS-CoV-2.” A few days later, Emory licensed the molecule to Ridgeback Biotherapeutics, a Miami-based biotechnology company which had previously developed a monoclonal antibody for Ebola.

Ridgeback partnered with the pharmaceutical giant Merck to accelerate its development.The Emory researchers named their drug molnupiravir, after Mjölnir—the hammer of Thor. It turns out that this was not hyperbole. Last month, Merck and Ridgeback announced that molnupiravir could reduce by half the chances that a person infected by the coronavirus would need to be hospitalized. The drug was so overwhelmingly effective that an independent committee asked the researchers to stop their Phase III trial early—it would have been unethical to continue giving participants placebos.

None of the nearly four hundred patients who received molnupiravir in the trial went on to die, and the drug had no major side effects. On November 4th, the U.K. became the first country to approve molnupiravir; many observers expect that an emergency-use authorization will come from the U.S. Food and Drug Administration in December.

Oral antivirals like molnupiravir could transform the treatment of COVID-19, and of the pandemic more generally. Currently, treatments aimed at fighting COVID—mainly monoclonal antibodies and antiviral drugs like remdesivir—are given through infusion or injection, usually in clinics or hospitals. By the time people manage to arrange a visit, they are often too sick to receive much benefit. Molnupiravir, however, is a little orange pill.

A person might wake up, feel unwell, get a rapid COVID test, and head to the pharmacy around the corner to pick up a pack. A full course, which needs to start within five days of the appearance of symptoms, consists of forty pills—four capsules taken twice a day, for five days. Merck is now testing whether molnupiravir can prevent not just hospitalization after infection but also infection after exposure.

If that’s the case, then the drug might be taken prophylactically—you could get a prescription when someone in your household tests positive, even if you haven’t.Molnupiravir is—and is likely to remain—effective against all the major coronavirus variants. In fact, at least in the lab, it works against any number of RNA viruses besides SARS-CoV-2, including Ebola, hepatitis C, R.S.V., and norovirus. Instead of targeting the coronavirus’s spike protein, as vaccine-generated antibodies do, molnupiravir attacks the virus’s basic replication machinery. The spike protein mutates over time, but the replication machinery is mostly set in stone, and compromising that would make it hard for the virus to evolve resistance.

Once it’s inside the body, molnupiravir breaks down into a molecule called NHC. As my colleague Matthew Hutson explained, in a piece about antiviral drugs published last year, NHC is similar to cytosine, one of the four “bases” from which viral RNA is constructed; when the coronavirus’s RNA begins to copy itself, it slips into cytosine’s spot, in a kind of “Freaky Friday” swap. The molecule evades the virus’s genetic proofreading mechanisms and wreaks havoc, pairing with other bases, introducing a bevy of errors, and ultimately crashing the system.

A drug that’s so good at messing with viral RNA has led some to ask whether it messes with human DNA, too. (Merck’s trial excluded pregnant and breast-feeding women, and women of childbearing age had to be on contraceptives.) This is a long-standing concern about antiviral drugs that introduce genomic errors. A recent study suggests that molnupiravir, taken at high doses and for extended periods, can, in fact, introduce mutations into DNA. But, as the biochemist Derek Lowe noted, in a blog post for Science, these findings probably don’t apply directly to the real-world use of molnupiravir in COVID patients. The study was conducted in cells, not live animals or humans.

The cells were exposed to the drug for more than a month; even at the highest doses, it caused fewer mutations than were created by a brief exposure to ultraviolet light. Meanwhile, Merck has run a battery of tests—both in the lab and in animal models—and found no evidence that molnupiravir causes problematic mutations at the dose and duration at which it will be prescribed.With winter approaching, America is entering another precarious moment in the pandemic. Coronavirus cases have spiked in many European countries—including some with higher vaccination rates than the U.S.—and some American hospitals are already starting to buckle under the weight of a new wave. Nearly fifty thousand Americans are currently hospitalized with COVID-19.

It seems like molnupiravir is arriving just when we need it.It isn’t the only antiviral COVID pill, either. A day after the U.K. authorized Merck’s drug, Pfizer announced that its antiviral, Paxlovid, was also staggeringly effective at preventing the progression of COVID-19 in high-risk patients. The drug, when taken within three days of the onset of symptoms, reduced the risk of hospitalization by nearly ninety per cent. Only three of the nearly four hundred people who took Paxlovid were hospitalized, and no one died; in the placebo group, there were twenty-seven hospitalizations and seven deaths. Paxlovid is administered along with another antiviral medication called ritonavir, which slows the rate at which the former drug is broken down by the body.

Like Merck, Pfizer is now examining whether Paxlovid can also be used to prevent infections after an exposure. Results are expected early in 2022. (It’s not yet known how much of a difference the drugs will make for vaccinated individuals suffering from breakthrough infections; Merck’s and Pfizer’s trials included only unvaccinated people with risk factors for severe disease, such as obesity, diabetes, or older age. Vaccinated individuals are already much less likely to be hospitalized or die of COVID-19.)

Living in an Age of ExtinctionPaxlovid interrupts the virus’s replication not by messing with its genetic code but by disrupting the way its proteins are constructed. When a virus gets into our cells, its RNA is translated into proteins, which do the virus’s dirty work. But the proteins are first built as long strings called polypeptides; an enzyme called protease then slices them into the fragments from which proteins are assembled.
If you can’t cut the plywood, you can’t build the table, and Paxlovid blunts the blade. Because they employ separate mechanisms to defeat the virus, Paxlovid and molnupiravir could, in theory, be taken together. Some viruses that lead to chronic infections, including H.I.V. and hepatitis C, are treated with drug cocktails to prevent them from evolving resistance against a single line of attack. This approach is less common with respiratory viruses, which don’t generally persist in the body for long periods.
But combination antiviral therapy against the coronavirus could be a subject of study in the coming months, especially among immunocompromised patients, in whom the virus often lingers, allowing it the time and opportunity to generate mutations.

Merck will be producing a lot of molnupiravir. John McGrath, the company’s senior vice-president of manufacturing, told me that Merck began bolstering its manufacturing capacity long before the Phase III trial confirmed how well the drug worked. Normally, a company assesses demand for a product, then brings plants online slowly. For molnupiravir, Merck has already set up seventeen plants in eight countries across three continents. It now has the capacity to produce ten million courses of treatment by the end of this year, and at least another twenty million next year.

It expects molnupiravir to generate five to seven billion dollars in revenue by the end of 2022.How much will all these pills soften the looming winter surge? As has been true throughout the pandemic, the answer depends on many factors beyond their effectiveness. The F.D.A. could authorize molnupiravir within weeks, and Paxlovid soon afterward. But medications only work if they make their way into the body. Timing is critical. The drugs should be taken immediately after symptoms start—ideally, within three to five days. Whether people can benefit from them depends partly on the public-health infrastructure where they live. In Europe, rapid at-home COVID tests are widely available.

Twenty months into the pandemic, this is not the case in much of the U.S., and many Americans also lack ready access to affordable testing labs that can process PCR results quickly.Consider one likely scenario. On Monday, a man feels tired but thinks little of it. On Tuesday, he wakes up with a headache and, in the afternoon, develops a fever. He schedules a COVID test for the following morning. Two days later, he receives an e-mail informing him that he has tested positive. By now, it’s Friday afternoon. He calls his doctor’s office; someone picks up and asks the on-call physician to write a prescription. The man rushes to the pharmacy to get the drug within the five-day symptom-to-pill window.

Envision how the week might have unfolded for someone who’s uninsured, elderly, isolated, homeless, or food insecure, or who doesn’t speak English. Taking full advantage of the new drugs will require vigilance, energy, and access.Antivirals could be especially valuable in places like Africa, where only six per cent of the population is fully vaccinated. As they did with the vaccines, wealthy countries, including the U.S. and the U.K., have already locked in huge contracts for the pills; still, Merck has taken steps to expand access to the developing world.

It recently granted royalty-free licenses to the Medicines Patent Pool, a U.N.-backed nonprofit, which will allow manufacturers to produce generic versions of the drug for more than a hundred low- and middle-income countries. (Pfizer has reached a similar agreement with the Patent Pool; the company also announced that it will forgo royalties for Paxlovid in low-income countries, both during and after the pandemic.) As a result, a full course of molnupiravir could cost as little as twenty dollars in developing countries, compared with around seven hundred in the U.S. “Our goal was to bring this product to high-, middle-, and low-income countries at fundamentally the same time,” Paul Schaper, Merck’s executive director of global pharmaceutical policy, told me.

More than fifty companies around the world have already contacted the Patent Pool to obtain a sublicense to produce the drug, and the Gates Foundation has pledged a hundred and twenty million dollars to support generic-drug makers. Charles Gore, the Patent Pool’s executive director, recently said that, “for large parts of the world that have not got good vaccine coverage, this is really a godsend.” Of course, the same challenges of testing and distribution will apply everywhere.

Last spring, as a doctor caring for COVID patients, I was often dismayed by how little we had to offer. We tried hydroxychloroquine, blood thinners, and various oxygen-delivery devices and ventilator maneuvers; mostly, we watched as patients got better or got worse on their own. In the evenings, as I walked the city’s deserted streets, I often asked myself what kinds of treatment I wished we had. The best thing, I thought, would be a pill that people could take at home, shortly after infection, to halt the cascade of biological processes that sends them to the hospital, the I.C.U., or worse.

We will soon have not one but two such treatments. Outside of the vaccines, the new antiviral drugs are the most important pharmacologic advance of the pandemic. As the coronavirus becomes endemic, we’ll need additional tools to treat the inevitable infections that will continue to strike both vaccinated and unvaccinated people. These drugs will do that, reducing the damage that the coronavirus can inflict and, possibly, cordoning off avenues through which it can spread. Still, insuring that they are meaningfully and equitably used will require strength in the areas in which the U.S. has struggled: early and accessible testing; communication and coördination across health-care providers; fighting misinformation and building trust in rapid scientific advances. Just as vaccines don’t help without shots in arms, antivirals can’t work without pills in people.

 

Source: https://www.newyorker.com/

More on the Coronavirus

Inside the Global Quest to Trace the Origins of COVID19 and Predict Where It Will Go Next

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It wasn’t greed, or curiosity, that made Li Rusheng grab his shotgun and enter Shitou Cave. It was about survival. During Mao-era collectivization of the early 1970s, food was so scarce in the emerald valleys of southwestern China’s Yunnan province that farmers like Li could expect to eat meat only once a year–if they were lucky. So, craving protein, Li and his friends would sneak into the cave to hunt the creatures they could hear squeaking and fluttering inside: bats.

Li would creep into the gloom and fire blindly at the vaulted ceiling, picking up any quarry that fell to the ground, while his companions held nets over the mouth of the cave to snare fleeing bats. They cooked them in the traditional manner of Yunnan’s ethnic Yi people: boiled to remove hair and skin, gutted and fried. “They’d be small ones, fat ones,” says Li, now 81, sitting on a wall overlooking fields of tobacco seedlings. “The meat is very tender. But I’ve not been in that cave for over 30 years now,” he adds, shaking his head wistfully. “They were very hard times.”

China today bears little resemblance to the impoverished nation of Li’s youth. Since Deng Xiaoping embraced market reforms in 1979, the Middle Kingdom has gone from strength to strength. Today it is the world’s No. 2 economy and top trading nation. It has more billionaires than the U.S. and more high-speed rail than the rest of the world combined. Under current strongman President Xi Jinping, China has embarked on a campaign to regain “center place in the world.” Farmers like Li no longer have to hunt bats to survive.

Dubbed RaTG13, Shi’s virus has a 96.2% similarity with the virus that has claimed some 600,000 lives across the world, including more than 140,000 in the U.S. Shi’s discovery indicates COVID-19 likely originated in bats–as do rabies, Ebola, SARS, MERS, Nipah and many other deadly viruses.

But how did this virus travel from a bat colony to the city of Wuhan, where the coronavirus outbreak was first documented? And from there, how did it silently creep along motorways and flight routes to kill nurses in Italy, farmers in Brazil, retirees in Seattle? How this virus entered the human population to wreak such a devastating toll is the foremost issue of global scientific concern today. The search for “patient zero”–or the “index case,” the first human COVID-19 infection–matters. Not because any fault or blame lies with this individual, but because discovering how the pathogen entered the human population, and tracing how it flourished, will help the science and public-health communities better understand the pandemic and how to prevent similar or worse ones in the future.

On top of the millions of lives that hang in the balance, Cambridge University puts at $82 trillion across five years the cost to the global economy of the current pandemic. The human race can ill afford another.

The provenance of COVID-19 is not only a scientific question. The Trump Administration also regards it as a political cudgel against Beijing. As the U.S. has failed to control outbreaks of the coronavirus and its economy founders, President Donald Trump has deflected blame onto China.

Trump and senior Administration figures have dubbed COVID-19 the “China virus” and “Wuhan virus.” Secretary of State Mike Pompeo said there was “enormous evidence” the virus had escaped from Shi’s lab in the city. (He has yet to share any hard evidence.) “This is the worst attack we’ve ever had on our country. This is worse than Pearl Harbor. This is worse than the World Trade Center,” Trump said in May of the pandemic, pointing the finger at China. In response, Chinese Foreign Minister Wang Yi accused the U.S. President of trying to foment a “new cold war” through “lies and conspiracy theories.”

The origin of the virus is clearly a touchy subject. Nevertheless, the world desperately needs it broached. Australia and the E.U. have joined Washington’s calls for a thorough investigation into the cause of the outbreak. On May 18, Xi responded to pressure to express support for “global research by scientists on the source and transmission routes of the virus” overseen by the World Health Organization.

Partisan bickering and nationalism threaten to eclipse the invaluable scientific work required to find the true source of the virus. Time is of the essence; a SARS vaccine was within touching distance when research that could have proved invaluable today was discontinued as the crisis abated. “Once this pandemic settles down, we’re going to have a small window of opportunity to put in place infrastructure to prevent it from ever happening again,” says Dr. Maureen Miller, a Columbia University epidemiologist.

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The search for the virus’s origins must begin behind the squat blue-shuttered stalls at Wuhan’s Huanan seafood market, where the outbreak of viral pneumonia we now know as COVID-19 was first discovered in mid-December. One of the first cases was a trader named Wei Guixian, 57, who worked in the market every day, selling shrimp out of huge buckets. In mid-December she developed a fever she thought was a seasonal flu, she told state-run Shanghai-based the Paper. A week later, she was drifting in and out of consciousness in a hospital ward.

Of the first 41 patients hospitalized in Wuhan, 13 had no connection to the marketplace, including the very first recorded case. That doesn’t necessarily excuse the market as the initial point of zoonotic jump, though–we don’t know yet for certain how many COVID-19 cases are asymptomatic, but research suggests it could be as high as 80%. And, even if Huanan market wasn’t where the virus first infected humans, it certainly played a huge role as an incubator of transmission. At a Jan. 26 press conference, the Hong Kong Centre for Health Protection revealed 33 of 585 environmental samples taken after the market was shut Jan. 1 tested positive for the virus. Of these, 31 were taken in the western section where wildlife was sold.

In May, China acceded to demands for an independent inquiry after more than 100 countries supported a resolution drafted by the E.U. Still, President Xi insists it must be “comprehensive”–looking not just at China but also at how other nations responded to the WHO’s warnings–and cannot begin until after the pandemic has subsided. “The principles of objectivity and fairness need to be upheld,” Xi told the World Health Assembly. (Notably, inquiries into the 2009 H1N1 “swine flu” pandemic and 2014 West African Ebola outbreak began before the crises had abated.) According to past investigations’ protocols, teams are composed of independent public-health experts and former WHO staff appointed by the WHO based on member states’ recommendations. At a practical level, however, any probe within China relies on cooperation from Beijing, and it’s uncertain whether the U.S. will accept the findings of a body Trump has slammed for “severely mismanaging and covering up the spread of the coronavirus.”

Artwork by Brea Souders for TIME; Shutterstock (3)

There are many who look at where COVID-19 emerged and see something that can’t be just a co-incidence. In 2017, China minted its first biosecurity-level 4 (bsl-4) laboratory–the highest level cleared to even work with airborne pathogens that have no known vaccines–in Wuhan. Ever since, the country’s foremost expert on bat viruses has been toiling away inside the boxy gray buildings of the WIV. Indeed, when Shi first heard about the outbreak, she herself thought, “Could they have come from our lab?” she recently told Scientific American. An inventory of virus samples reassured her that it hadn’t, she added, yet that hasn’t stopped some from maintaining their suspicions.

Mistakes do happen. The last known case of small-pox leaked from a U.K. laboratory in 1978. SARS has leaked from Chinese laboratories on at least two occasions, while U.S. scientists have been responsible for mishandlings of various pathogens, including Ebola. There are only around 70 bsl-4 laboratories in 30 countries. Suspicions regarding the nature of research under way inside the Wuhan laboratory persist. According to one leading virologist, who asked to remain anonymous for fear of jeopardizing funding and professional relationships, “Were you to ask me where’s the most likely place in the world for a naturally occurring bat coronavirus to escape from a laboratory, Wuhan would be in the top 10.”

Still, neither the WHO nor the Five Eyes intelligence network–comprising the U.S., U.K., Canada, Australia and New Zealand–has found evidence that COVID-19 originated from Shi’s lab. Canberra has even distanced itself from a U.S.-authored dossier that sought to convince the Australian public that the Five Eyes network had intelligence of a Chinese cover-up. (It appeared to rely exclusively on open-source material.) Meanwhile, scientific peers have rallied to defend Shi from suspicion. “She is everything a senior scientist should be,” says Miller, who has collaborated with Shi on various studies. The Wuhan Institute of Virology did not respond to requests for comment.

Available evidence suggests COVID-19 leaped from wild animal to human. Tracing exactly how is crucial. It enables governments to install safeguards regarding animal husbandry and butchery to prevent any repeat. SARS, for example, originated in bats and then infected a palm civet, a catlike mammal native to South and Southeast Asia. The animal was then sold at a wet market–where fresh meat, fish and sometimes live animals are sold–in Guangdong, from which it jumped to humans. In the wake of that outbreak, which claimed at least 774 lives worldwide, palm civets were banned from sale or consumption in China. Bats may have been the initial reservoir for SARS-CoV-2, but it’s likely that there was an intermediary before it got to humans, and that’s where the possibilities grow. Bats share Shitou Cave with starlings, for one, and at least one large white owl nests in its upper reaches. Herds of black and white goats graze the dusty shrub all around the cave opening, while the Yi ethnic group traditionally rear and eat dogs. Bat guano is also traditionally prized as a fertilizer on crops.

That COVID-19 originated in bats and then jumped to humans via a pangolin intermediary is now the most likely hypothesis, according to multiple studies (although some virologists disagree). Up to 2.7 million of the scaly mammals have been plucked from the wild across Asia and Africa for consumption mostly in China, where many people believe their scales can treat everything from rheumatoid arthritis to inflammation. Their meat is also highly prized for its supposed health benefits.

On Feb. 24, China announced a permanent ban on wildlife consumption and trade, scratching out an industry that employs 14 million people and is worth $74 billion, according to a 2017 report commissioned by the Chinese Academy of Engineering. It’s again extremely sensitive. President Xi is an ardent supporter of TCM and has promoted its use globally. The total value of China’s TCM industry was expected to reach $420 billion by the end of this year, according to a 2016 white paper by China’s State Council. And rather than raising the possibility that misuse of TCM sparked the outbreak, Chinese state media has lauded–without evidence–the “critical role” TCM has played in the treatment of COVID-19 patients. In an apparent attempt to head off criticism related to the pandemic, draft legislation was published in late May to ban any individual or organization from “defaming” or “making false or exaggerated claims” about TCM. Cracking down on the illicit animal trade would go a long way toward preventing future outbreaks. But as demand for meat grows across increasingly affluent Asia, Africa and Latin America, the potential for viruses to spill over into human populations will only increase.

It probably wasn’t blind luck that Li and his friends didn’t get sick from their hunting expeditions in Shitou Cave. Research by Columbia’s Miller with WIV’s Shi, published in 2017, found that local people were naturally resistant to SARS-like viruses. Examining their lifestyle habits and antibodies can help deduce both mitigating factors and possible therapies, while pinpointing which viruses are particularly prone to infecting humans, potentially allowing scientists to design vaccines in advance. “They are the canaries in the coal mine,” says Miller.

The page signaled the first confirmed U.S. case of COVID-19. The patient was a Washington State resident who had recently returned from visiting family in Wuhan, where the disease was spreading rapidly. Aware of his higher risk, and concerned when he developed a fever, the 35-year-old (who wishes to remain anonymous) visited an urgent-care center where he told health care providers about his travel history. They notified the state health department, which in turn helped the care center send a sample for testing to the Centers for Disease Control and Prevention (CDC) in Atlanta–at the time, the only labs running COVID-19 tests. When the test was positive, CDC scientists recommended the patient be hospitalized for observation. And Diaz’s team was paged.

A trained ambulance team arrived at the man’s home, moved him into a specially designed mobile isolation unit, and drove 20 minutes to Providence Regional. There, the patient couldn’t see who greeted him; everyone assigned to his care was garbed in layers of personal protective equipment. Once in his room, he spoke to medical staff only through a tele-health robot equipped with a screen that displayed their faces, transmitted from just outside the room.

A nurse carefully swabbed the back of his nose and pharynx for a sample of the virus that had brought him to the hospital. Not only was he the first confirmed case of COVID-19 in the U.S., he was also the first in the country to have his virus genetically sequenced. As the index patient in the U.S., his sequence, named WA1 (Washington 1), served as the seed from which experts would ultimately trace the genetic tree describing SARS-CoV-2’s path from person to person across communities, countries and the globe, as it mutated and either died out or moved on with renewed vigor to infect more people.

Genetic sequencing is a powerful tool to combat viruses’ fondness for mutating. Viruses are exploitative and unscrupulous; they don’t even bother investing in any of their own machinery to reproduce. Instead, they rely on host cells to do that–but it comes at a price. This copying process is sloppy, and often leads to mistakes, or mutations. But viruses can sometimes take advantage of even that; some mutations can by chance make the virus more effective at spreading undetected from host to host. SARS-CoV-2 seems to have landed on at least one such suite of genetic changes, since those infected can spread the virus even if they don’t have any symptoms.

Since the first SARS-CoV-2 genome was published and made publicly available online in January, scientists have mapped the genomes of over 70,000 (and counting) samples of the virus, from patients in China, the U.S., the E.U., Brazil and South Africa, among others. They deposited those sequences into the Global Initiative on Sharing All Influenza Data (GISAID), a publicly available genetic database created in 2008 initially to store and share influenza genomes. During the coronavirus pandemic, it has quickly pivoted to become a clearinghouse for tracking the genetics of SARS-CoV-2, enabling scientists to map the virus’s march across continents and detail its multipronged attack on the world.

“We have genomes from researchers and public-health labs from all over the world on six continents,” says Joel Wertheim, associate professor of medicine at University of California, San Diego. “It provides us with unique insight and confidence that other types of epidemiological data just cannot supply.” Relying on the GISAID sequences, Nextstrain has become a virtual watering hole for scientists–and increasingly public-health officials–who want to view trends and patterns in the virus’s genetic changes that can help inform decisions about how to manage infections.

If genetic sequencing is the new language for managing infectious-disease outbreaks, then the mutations that viruses generate are its alphabet. If paired with information on how infected patients fare in terms of their symptoms and the severity of their illness, genomic surveillance could reveal useful clues about which strains of virus are linked to more severe disease. It might shed light on the mystery of why certain victims of the virus are spared lengthy hospital stays and life-threatening illness. As nations start to reopen, and before a vaccine is widely available, such genetic intel could help health care providers to better plan for when and where they will need intensive-care facilities to treat new cases in their community.

Genetic information is also critical to developing the most effective drugs and vaccines. Knowing the sequence of SARS-CoV-2 enabled Moderna Thera-peutics to produce a shot ready for human testing in record time: just two months from when the genetic sequence of SARS-CoV-2 was first posted. Even after a vaccine is approved and distributed, continuing to track genetic changes in SARS-CoV-2 to ensure it’s not mutating to resist vaccine-induced immunity will be critical. The data collected by Nextstrain will be crucial to help vaccine researchers tackle mutations, potentially for years to come. Already, the group advises the WHO on the best genetic targets for the annual flu shot, and it plans to do the same for COVID-19. “We can track the areas of the virus targeted by the vaccine, and check the mutations,” says Emma Hodcroft from the University of Basel, who co-developed Nextstrain. “We can predict how disruptive those mutations are to the vaccine or not and tell whether the vaccines need an update.”

After Diaz’s patient tested positive for SARS-CoV-2, Washington State public-health officials diligently traced the places the patient had been and the people he’d come in contact with. He had taken a ride-share from the airport, gone to work and enjoyed lunch at a seafood restaurant near his office with colleagues. But because so little was known about the virus at the time, these contact tracers were focusing mostly on people with symptoms of illness–and at the time, none of the patient’s contacts reported them. The genetics, however, told a different story.

Seattle happened to have launched a program in 2018 to track flu cases by collecting samples from patients in hospitals and doctors’ offices, sites on college campuses, homeless shelters, the city’s major international airport and even from volunteers with symptoms who agreed to swab their nasal passages at home. Those that were positive for influenza and other respiratory illnesses had their samples genetically sequenced to trace the diseases’ spread in the community. As COVID-19 began to emerge in the Seattle area at the end of February, Bedford and his colleagues began testing samples collected in this program for SARS-CoV-2, regardless of whether people reported symptoms or travel to China, then the world’s hot spot for the virus. That’s how they found WA2, the first case in Washington that wasn’t travel-related. By comparing samples from WA1, WA2 and other COVID-19 cases, they figured out that SARS-CoV-2 was circulating widely in the community in February.

If that community-based sequencing work had been conducted earlier, there’s a good chance it might have picked up cases of COVID-19 that traditional disease-tracking methods, which at the time focused only on travel history and symptoms, missed. That would have helped officials make decisions about a lockdown sooner, and might have helped to limit spread of the virus. SARS-CoV-2 moves quickly but mutates relatively slowly, for a virus–generating only about two mutations every month in its genome. For drug and vaccine developers, it means the virus can still evade new treatments designed to hobble it. Those same changes serve as passport stamps for its global trek through the world’s population, laying out the itinerary of the virus’s journey for geneticists like Bedford. The cases in the initial Seattle cluster, he says, appear to have all been connected, through a single introduction directly from China to the U.S. in mid- to late January. Until the end of February, most instances of SARS-CoV-2 in the U.S. piggybacked on unwitting travelers from China. But as the pandemic continued, that changed.

Bedford’s team began to see mutations in samples from Seattle that matched samples from people in Europe and the U.S.’s East Coast. “At the beginning we could kind of draw a direct line from viruses circulating in China to viruses circulating in the Seattle area,” says Bedford. “Later, we see that viruses collected from China have some mutations that were seen later in Europe, and those same mutations were seen in viruses in New York. So, we can draw another line from China to Europe to New York” and then on to Seattle. The virus had begun multiple assaults into the U.S.

TIME Graphic by Emily Barone and Lon Tweeten

Around the world, virologists were seeing similar stories written in the genes of SARS-CoV-2. In January, a couple from Hubei province arrived in Rome, eager to take in the sights of the historic European city. By Jan. 29, they were hospitalized at Lazzaro Spallanzani National Institute for Infectious Diseases with fever and difficulty breathing. Tests confirmed they were positive for SARS-CoV-2.

Bartolini, a virologist at the hospital, and her colleagues compared the genetic sequences from a sample taken from the wife to sequences posted on GISAID. The Italian researchers found it matched five other samples from patients as far-flung as France, Taiwan, the U.S. and Australia. SARS-CoV-2 was clearly already on a whirlwind tour of the planet.

Not all strains of SARS-CoV-2 are equally virulent; some branches of its genetic tree are likely to grow larger and sprout further offshoots, while others terminate more quickly, says Harm van Bakel, assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai. His team conducted the first genetic sequencing analysis of cases in New York City, which quickly became a U.S. hot spot; by March the city had seen a half a dozen or so separate introductions of SARS-CoV-2, but only two resulted in massive spread of the virus. The remainder petered out without transmitting widely.

Retrospectively, there’s no way to tell for sure if these two strains were simply in the right place at the right time–in a particularly densely populated area of the city, for example, or in an area where people congregated and then dispersed to other parts of the city–or if they were actually more infectious. But determining the genetic code of a circulating virus early may help scientists and governments decide which strains are worth worrying about and which aren’t.

From analyzing genetic sequences from 36 samples of patients in Northern California, Dr. Charles Chiu, professor of laboratory medicine and infectious diseases at the University of California, San Francisco, says it might have been possible to identify the major circulating strains and track how they spread if more testing were available to know who was infected–and use this information to guide quarantine and containment practices. “There was a window of opportunity that if we had more testing and more contact-tracing capacities available early on, we likely would have prevented the virus from gaining a foothold at least in California,” he says.

Ongoing genetic sequencing can also help officials tailor narrower strategies to quell the spread of a virus. It wasn’t long after Beijing reopened following two months of lockdown that infections began creeping up again in June. Sequencing of the new cases revealed that the viruses circulating at the time shared similarities with viruses found in patients in Europe, suggesting the cases were new introductions of SARS-CoV-2 and not lingering virus from the original outbreak. That helped the Chinese government decide to implement only limited lockdowns and testing of people in specific apartment blocks around a food market where the cluster of cases emerged, rather than resort to a citywide quarantine.

And there are other, less obvious ways that genetic analysis of SARS-CoV-2 could help to predict surges in cases as people emerge from lockdown. Italian scientists have sampled wastewater from sewage treatment plants in northern cities where the pandemic flourished, and found evidence of SARS-CoV-2 weeks before the first cases showed up to flood the hospitals. In La Crosse, Wis., Paraic Kenny, director of the Kabara Cancer Research Institute of the Gundersen Health System, applied the same strategy in his hometown in the spring. A few weeks later, in mid-June, when cases of COVID-19 surged because of bars reopening in downtown La Crosse, Kenny compared samples from infected people with the viral genomes in his wastewater samples. They were a genetic match. The same strain of SARS-CoV-2 had been circulating in the community weeks before the cases were reported. “In principle, an approach like this can be used to not just ascertain how much virus is in the community, but maybe give hospitals and public-health departments a warning of when to anticipate a surge in cases,” he says. The goal is to know not just where we are today but where we will be a week or two from now.

It has been 100 years since an infectious disease pushed the entire world’s population into hiding to the extent that COVID-19 has. And the primary approaches we take to combatting emerging microbes today are likewise centuries old: quarantine, hygiene and social distancing. We may never learn exactly where SARS-CoV-2 came from, and it’s clearly too late to prevent it from becoming a global tragedy. But extraordinary advances in scientific knowledge have given us new tools, like genetic sequencing, for a more comprehensive understanding of this virus than anyone could have imagined even a decade or two ago. These are already providing clues about how emerging viruses like SARS-CoV-2 operate and, most important, how they can be thwarted with more effective drugs and vaccines.

BY CHARLIE CAMPBELL/ YUXI, YUNNAN AND ALICE PARK

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A Virologist Explains Why It Is Unlikely COVID-19 Escaped From A Lab

Nearly five months into the first coronavirus pandemic, the debate rages on over the source of SARS-CoV-2, the virus that causes COVID-19. An early cluster of cases, linked to an animal market in Wuhan, initially suggested that humans had been infected by animals. Due to the nature of wet markets, it appeared that animals held in close proximity to each other may have provided a unique opportunity for the virus to jump from species to species (as happened with SARS).

But a growing number of conspiracy theories have emerged through misinformation campaigns, from blaming a nefarious bioengineered virus to the emergence of 5G as the cause of COVID-19. These theories, however, aren’t borne out by the evidence. The most likely origin, supported by the vast majority of scientists around the world, doesn’t involve cell towers or mad scientists or even wild animal markets.

In fact, it is quite simple: the virus likely came from bats.

How do we know that SARS originated from bats?

In general, diseases do not spontaneously jump between species. But bats, particularly fruit bats, are an exception to this rule. They are uniquely able to serve as hosts for viruses that can break that barrier. Human history has many examples of this including the filoviruses (which can cause hemorrhagic fevers like in Ebola) and henipaviruses, which have caused small but deadly disease outbreaks in Australia and Asia. Better-known viruses that come from bats are coronaviruses, which cause respiratory infections.

Recent technological advancements like deep sequencing have been used to detect and sequence the virus that causes COVID-19, as well as other viruses acquired from bat samples in the field. These investigations have provided detailed information regarding the diversity of viruses found within bats as well as their evolutionary history. Indeed, bats are the likely reservoir for SARS-CoV-2 given the similarity of the virus to bat SARS-CoV-like coronaviruses.

What do we know the virus didn’t escape from a lab?

While there is growing consensus and scientific evidence that SARS-CoV-2 originated in bats, there is a growing chorus of questions regarding the nature of spillover into humans. A recent report raised the specter of a laboratory escape of the virus based on US State Department cables from 2018. At the time, the department raised safety concerns regarding the Wuhan Institute for Virology, a high-containment laboratory.

Indeed, accidental laboratory exposures and escapes have occurred in the past, including the influenza virus and SARS-CoV. However, this week the chairman of the joint chiefs of staff echoed that the weight of evidence continued to suggest natural rather than accidental emergence for SARS-CoV-2. There has been no other science supporting the escape theory. Research continues to point to identifying the reservoir host and potential intermediate host(s) for SARS-CoV-2 as this remains the most plausible explanation for emergence of the virus.

How do we know it didn’t come from the animal markets?

Though environmental samples from the Wuhan animal market tested positive for SARS-Co-2, no animal samples have tested positive. More recent evidence suggests that the virus had been circulating in the Hubei province as early as November 2019, which predates evidence of the virus at the Wuhan market. Consequently, the more likely explanation is that it appeared in the market in December 2019 via human-to-human spread.

Could the virus have come from pangolins?

But what about the curious case of pangolins? Coronaviruses similar to SARS-CoV-2 have been identified in Malayan pangolins, a small scaly mammal native to Asia. The identified pangolin coronaviruses have 85.5% to 92.4% genomic similarity to SARS-CoV-2. This similarity is a close second to the recently identified bat coronavirus RaTG13, which is 96% similar. This has led to speculation that pangolins may be a potential intermediate host for SARS-CoV-2, but there’s no definitive finding as of yet. But even if humans got SARS-CoV-2 from pangolins, its ultimate origin is still likely to be bats.

If this is such a problem, could we just outlaw the sale and consumption of wild animals?

Although the consumption of wild meat certainly presents the opportunity for zoonotic viruses to transmit to humans, most transmission is caused by urban sprawl as humans increasingly come in contact with animals. Deforestation and climate change have minimized the ecological niches of wildlife, including the migratory range of bats, forcing animals to come into closer and closer contact with humans.

Wild meat, including bats, remain important sources of nutrition for people in many parts of the world. Without proper education campaigns and accessible alternatives for food, banning the sale and consumption of wild animals could prove catastrophic. As many individuals rely on their consumption for income and sustenance, it would likely drive these activities underground. That would make tracing the source of animal to human transmissions even more difficult to identify and prevent.

So how can we stop bats from spreading disease?

Unfortunately, the answer is that we simply cannot. Bats comprise more than 20% of all known mammalian species and serve pivotal roles in our ecosystem and economy. Bats are responsible for controlling crop and forest pests, in addition to contributing to pollination and seed dispersal. In addition, human encroachment into bat habitats helps potentiate spillover events.

In response to COVID-19, many have called for bat habitats to be decimated or populations to be culled. But these activities would only serve to further threaten the food supply in areas already suffering from food insecurity. So while we still can not definitively answer where and when the SARS-CoV-2 spillover event from bats occurred, we do have a roadmap for containing future spillover events. It will require increased efforts of wildlife surveillance and their ever-changing habitats in order to develop tools to predict where and when these events are likely to occur. Only then will we be poised to act quickly and precisely when outbreaks occur.

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Dr. Jason Kindrachuk is an Assistant Professor in the Department of Medical Microbiology & Infectious Diseases, University of Manitoba, Canada, and holds a Tier 2 Canada Research Chair in the molecular pathogenesis of emerging and re-emerging viruses. He has broad expertise and interests in emerging viruses and pandemic/outbreak preparedness in both developing and developed nations. Importantly, he actively participates in multiple international scientific outreach activities to provide training and expertise to regional partners in Africa including Sierra Leone, Gabon and Kenya.

Source: A Virologist Explains Why It Is Unlikely COVID-19 Escaped From A Lab

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Jason Kindrachuk, an Assistant Professor at the University of Manitoba’s Department of Medical Microbiology & Infectious Diseases and Canada Research Chair joins CPAC’s Peter Van Dusen to speak about the approaching deal between Canada and the United States to close borders. Watch full episodes and more at http://www.cpac.ca/primetimepolitics Like this video? Subscribe to CPAC on YouTube: https://www.youtube.com/user/cpac/ Connect with us on… Twitter: https://twitter.com/PTP_CPAC Facebook: https://www.facebook.com/CPACTV Instagram: https://www.instagram.com/cpac_tv

Forget China’s ‘Excessive’ Coronavirus Surveillance—This Is America’s Surprising Alternative

Here’s an interesting twist. China has spent years building a vast surveillance state to digitally track its population, a system that has come to the fore in its attempts to monitor and control the spread of coronavirus. For years we have decried this “big brother” monitoring, and yet it turns out that we have a vast surveillance dataset of our own, just waiting for the government to tap into.

Last week, I reported on viral coronavirus maps that use marketing databases to show the movements of Americans as they congregate and disperse, illustrative of the potential spread of coronavirus infections. The granularity of the data shocked many—although the subject matter distracted most from the underlying issue. The data is unique to individuals but claims anonymity—however, last year the New York Times exposed just how easily that veil is broken.

It is therefore a surprise that the U.S. government—through the Centers for Disease Control and Prevention, has elected to use this marketing dataset rather than mobile operator data to track coronavirus. “Officials across the U.S. are using location data from millions of cellphones,” the Wall Street Journal reported on March 28, “to better understand the movements of Americans during the pandemic.” The newspaper says the plan is “to create a portal for federal, state and local officials that contains geolocation data in what could be as many as 500 cities across the U.S.”

When coronavirus first hit China, the country repurposed its surveillance state into a contact tracing and quarantine enforcement machine. The infrastructure was in place. Facial and license plate recognition, contact tracing and phone tracking, proximity reports from public transportation, apps to determine quarantine status and freedom of movement, and social media to inform on rule-breakers. Described as “excessive coronavirus public monitoring,” it is expanding China’s already pervasive use of biometric people tracking technologies.

In the West we have no such biometric-powered surveillance state, whatever campaign groups might say. There is the rule of law, warranted tracking, even campaigns to remove facial recognition from law enforcement. Meanwhile, we all carry smartphones loaded with apps that we give permission to track us, wherever we go and whenever we go there, down to a frightening level of detail.

Smartphone tracking is becoming the front-end for coronavirus population tracking—be that individuals confined to their homes, curfews, contact tracing or aggregated analysis on the impact of social distancing. A smartphone is a proxy for a person. Track the phones and you track the people. Each device can be uniquely tied to its owner, whether in Beijing or Boston, Shanghai or Seattle.

In the U.K. and mainland Europe, governments and the European Union have pulled data from the mobile network operators themselves to track millions of citizens, aggregated and anonymized, monitoring adherence with social distancing and travel restrictions. There was even talk that the GSMA might develop a centralised data program across 700 operators to track users cross-border.

Mobile networks hold significant data on customers. Location pings, call and messaging metadata, obviously the identities behind the numbers and whatever their CRM systems store. This data has its limitations. It is also heavily regulated, protected from prying eyes except under legally warranted circumstances.

There is however an even larger dataset that has no such regulatory limitations. It contains information on all of us—we actually give it permission to collect our locations, our browsing activities, where we go, when, how often. The information can be mined to infer where we work and live, what we like to do and with who. It is the closest we have to a surveillance state—and it’s now everywhere.

The database is fuelled by the apps on our smartphones—apps we give permission to access data they do not need to execute their own functions. And that data can be sold to create a revenue stream for its operators. Last year, one project set out to show just how out of hand this has become. A security researcher tested 937 Android flashlight apps—the most innocuous apps imaginable, of which 180 requested permission to access our contacts and 131 our precise locations.

This marketing data source, which gathers information on all of us, all of the time, is quite the surveillance feat. If any western government set out its intention to build such a platform there would be an extraordinary public backlash. And yet the data is there and can be accessed commercially for just the payment of a fee.

Once the pandemic is behind us, the memory of those maps tracking us coast to coast will remain. And as we look to the east, to its vast government surveillance ecosystem, perhaps we will recall the equivalent we live with ourselves. The fact is that the necessity of the coronavirus pandemic has pushed government invention into new and surprising areas. And from a surveillance stance, one of the most powerful ways imaginable has been there all the time.

It is clear that over the coming weeks we will be asked to further trade personal privacy for public safety. Those datasets can be mined for ever more powerful information—the same contact tracing and quarantine breaches China monitors. According to the WSJ, the mobile ad data “can reveal general levels of compliance with stay-at-home or shelter-in-place orders—and help measure the pandemic’s economic impact by revealing the drop-off in retail customers at stores, decreases in automobile miles driven and other economic metrics.”

Not bad for a ready-made, off-the-shelf alternative.

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I am the Founder/CEO of Digital Barriers—developing advanced surveillance solutions for defence, national security and counter-terrorism. I write about the intersection of geopolitics and cybersecurity, as well as breaking security and surveillance stories. Contact me at zakd@me.com.

Source: Forget China’s ‘Excessive’ Coronavirus Surveillance—This Is America’s Surprising Alternative

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