New Coronavirus News from 17 Apr 2022

Wild animals prized as delicacies in China contain a bevy of threatening viruses [Science Magazine, 17 Apr 2022]

BY JON COHEN

Wild animals sometimes found on the menu in China harbor a bewildering panoply of viruses, a new study has found—including many that can infect humans. Although none is closely related to the coronavirus that touched off the COVID-19 pandemic, the study sends a clear warning that other viral threats are lurking in the animal kingdom, scientists say.

Live-animal markets are known to have sparked outbreaks, such as severe acute respiratory syndrome (SARS) 2 decades ago. But the study underscores the extent of the threat, showing“there is an enormous amount of unsampled viral diversity” in the animals, says Harvard University evolutionary biologist William Hanage, who was not involved in the work. “We humans need to understand that for a virus, different mammal species can look pretty alike, provided their cells have appropriate receptors.” China has clamped down on the sale of the animals sampled in the study, but other countries in the region have not.

The researchers, led by veterinarian Su Shuo of Nanjing Agricultural University, took samples from nearly 2000 animals representing 18 different species at venues in China including fur farms, zoos, and natural habitats. Most were species that are traditionally eaten as delicacies in China, including civets, raccoon dogs, badgers, bamboo rats, and porcupines. Using a “metagenomics” technique, which probes samples for RNA transcripts that viruses make when they copy themselves, they identified 102 virus species from 13 different viral families in the animals’ noses, feces, and tissues. Sixty-five of the viruses had never been described before. The researchers deemed 21 as “high risk” to humans, because they had infected people in the past or simply had a history of readily jumping between species.

“Our results provide important insights to those game animals and their viruses that might lead to the next pandemic,” says Su, whose group published its work online yesterday in Cell.

Among the worrisome finds were several coronaviruses. For example, a hedgehog was infected with a virus resembling the one that causes Middle East respiratory syndrome in humans. Four canine coronaviruses found in raccoon dogs were about 94% similar to coronaviruses recently found in humans in Malaysia and Haiti. “These viruses can infect many animals,” Su says.

Some of the species sampled in the study could act as “intermediary” hosts that bat coronaviruses infect before they make the jump to humans. Indeed, a coronavirus close to one found in bats turned up in a civet. Most researchers think both SARS-CoV-2 and SARS-CoV-1—the cause of SARS—became human pathogens after passing through an intermediate host.

The researchers also detected several influenza viruses, another family that could trigger a new pandemic. In a finding “of considerable significance,” the authors write, civets and Asian badgers were found to carry H9N2, an influenza A virus that has become increasingly common in chickens and ducks. There have been fewer than 50 documented human cases of H9N2 infection, a February 2020 report noted, because the virus does not transmit efficiently between people. But researchers fear that by replicating in other mammals it has more opportunities both to infect humans and to adapt to them. The infected badgers had runny noses and presumably could transmit to humans through the respiratory route.

Other viruses detected in the study that can infect people include influenza B, Norwalk, human parainfluenza virus 2, rotaviruses, and orthoreoviruses.

Markets that sell live animals—often called “wet markets”—are ideal places for viruses to transmit to humans, both because of the density of animals and because the stress they suffer makes them prone to shedding viruses, says medical virologist Marietjie Venter of the University of Pretoria, Hatfield. The new findings “confirm that trade and consumption of these animals should be avoided and support the actions taken by China to ban the trade of many of these animals,” says Venter, who is a member of the World Health Organization’s Scientific Advisory Group for the Origins of Novel Pathogens.

After SARS, China made the sale of many of the animals sampled in the study illegal, but they were still readily available in Wuhan markets in 2019, just before the start of the pandemic, including at the Huanan Seafood Market, which had the earliest identified cluster of COVID-19 cases. Su says the government has cracked down hard on illegal sales since then. “With very strict legislation, as well as screening checks, it is now difficult to find wildlife” for sale, Su says.
“What worries me is that it seems that in Southeast Asia, where the economy is lagging, this wild animal trade is continuing.”

Evolutionary biologist Edward Holmes at the University of Sydney, a co-author of the new study, “strongly suspects” SARS-CoV-2 jumped into humans at the Huanan market. As long as wild animals are sold, the risk of similar jumps remains high, he says. “It’s hard to think of a more effective way to ignite and fan the flames of an epidemic,” Holmes says. “We keep allowing these things to flourish and it’s only a matter of time before we get another outbreak and perhaps another pandemic.”

Inland Empire residents celebrate Easter atop Mount Rubidoux, elsewhere [San Bernardino County Sun, 17 Apr 2022]

By DAVID DOWNEY

Christians throughout the Inland Empire celebrated Easter on Sunday, April 17, gathering on top of Riverside’s Mount Rubidoux and elsewhere for the inspirational holiday.

For the first time since the coronavirus pandemic struck and triggered limitations on large-group activities, the Mount Rubidoux sunrise service was celebrated without restriction as Riverside pastors spoke on the theme “Come to Jesus,” said event organizer Pastor Brenda Wood of Word of Life Ministries International. Congregating atop the mountain overlooking downtown Riverside as the sun comes up has been a tradition since 1909.

After two years of virtual and outdoor services, Purpose Church in Pomona welcomed people back inside for Easter worship, this time at its 11-acre campus. Prior to 2020, Purpose Church staged Easter services for more than 10,000 people at the Fairplex in Pomona.

The Redlands Community Resurrection Sunday Service drew a crowd of faithful to the Redlands Bowl. In Corona, Crossroads Christian Church held Easter services and displayed a Stations of the Cross art exhibit, chronicling the final hours of Jesus’ life. And for the 94th time, a sunrise service took place at the Ramona Bowl Amphitheatre near Hemet.

New Coronavirus News from 16 Apr 2022

Easter weekend Corona Calculus [WSAZ, 16 Apr 2022]

By Tony Cavalier

HUNTINGTON, W.Va. (WSAZ) -The pandemic is now more than 2 years old with America still weary of the spread of the Omnicom variant. Still there is room for cautious optimism this Easter compared to the past two but with important exceptions. After all many Americans (67%) are now fully vaccinated and as many as half of the population has been exposed to the virus (many asymptomatically). To describe the position of relative strength we are in, Tony offers a new episode in corona calculus where he calls about the Venn Diagram to support his thesis. Turns out whether you are through the 3 shot routine (PFIZER, MODERNA) or two shots with JNJ chances chances are very good you have immunity.

New Coronavirus News from 14 Apr 2022

Unethical studies of ivermectin for covid-19 [The BMJ, 14 Apr 2022]

by Gideon Meyerowitz-Katz, Sarah Wieten, María de Jesús Medina Arellanor, Gavin Yamey

Flawed research means we still do not know if the drug is safe or effective
During disease outbreaks, it can be tempting to sacrifice the scientific rigour of research in favour of speed, given the urgency to develop new treatments. After the 2014-16 Ebola outbreak in west Africa, however, a report on the ethics of research from the US National Academy of Medicine stated clearly that “research during an epidemic is still subject to the same core scientific and ethical requirements that govern all research on human subjects.”1

Early in the covid-19 pandemic ethicists warned researchers against “pandemic research exceptionalism”—lowering ethical standards because of the urgency of the crisis.2 Despite these warnings, there have been many examples of researchers treating covid-19 as exactly that: an exception to the rigorous standards to which we should hold medical research.3 There is no better example of such exceptionalism than the research into ivermectin for covid-19.

Ivermectin is used to treat a range of parasitic diseases, including onchocerciasis and helminthiases. On the basis of in vitro activity against SARS-CoV-2,4 the drug was tested as a possible treatment and prevention for covid-19. Initial randomised trials and systematic reviews suggested large benefits from the drug, including reduced hospital admissions and improved survival rates.56 It turns out that many of the results were—literally—too good to be true.7

An analysis of 26 major trials of ivermectin for covid-19 found that over one third had “serious errors or signs of potential fraud.”7 One prominent meta-analysis that suggested a large survival benefit from the drug was retracted.6 The authors did a re-analysis and found that the effect of ivermectin on survival that they had shown in their retracted study “was dependent on the inclusion of studies with a high risk of bias or potential medical fraud.”8 The editor of the American Journal of Therapeutics published an expression of concern about another high profile meta-analysis, noting suspicious data in several of the included studies and concluding that “exclusion of the suspicious data appears to invalidate the findings regarding ivermectin’s potential to decrease the mortality of covid-19 infection.”9

Ethics scandals
Two recent ethics scandals have cast a further shadow over ivermectin research. First, a report of an experimental study in Mexico City that gave almost 200 000 ivermectin based medical kits to residents with covid-19 was retracted from the preprint server SocArXiv.10 The report was retracted, says SocArXiv’s director, because the experiment was conducted “without proper consent or appropriate ethical protections.”11 Second, in an experiment in a jail in Arkansas, USA, four incarcerated men developed severe side effects after a physician gave them high dose ivermectin as a supposed covid-19 treatment without their knowledge.10 The four men are suing the jail.

Lack of consent was not the only ethical violation in these two scandals. The research participants were exposed to a risk of drug side effects without knowing they had been given ivermectin. In Mexico, the failure to give information to the participants infringed on a human right established in Mexico’s constitution: the right to access information.12 The Arkansas case raises additional concerns as it involved incarcerated people, who risk coercion and exploitation when they are enrolled in clinical research.

It is also arguably unethical and a waste of resources to conduct drug research in an emergency that is of such low quality that no conclusions can be drawn about the drug’s efficacy. That is the situation we find ourselves in today—it is still unclear whether ivermectin is safe or has any benefit in the treatment or prevention of covid-19.13 The flawed and potentially fraudulent research represents a huge missed opportunity to answer an important research question.

Abandoning research exceptionalism
The pressure to act quickly and do something instead of nothing in a global health emergency can lead researchers to cause harm or add to already existing injustices. But the answer is not to abandon research during crises, which could itself lead to “inadequate, ineffective, or even harmful care.”14 The answer is to abandon research exceptionalism.

Such exceptionalism is not needed to run fast, informative trials during a pandemic. The Recovery trial, for example, was a collaborative triumph that allowed clinicians quickly and efficiently to discard ineffective treatments such as lopinavir-ritonavir while adopting effective ones such as dexamethasone.1415 The trial started in March 2020 and released its first results in June 2020, finding an effective treatment for covid-19 just 10 weeks after enrolling the first participant while maintaining high ethical standards.16

The Nuffield Council on Bioethics has recommended several ways to conduct ethical research even under crisis conditions.17 These include research teams developing study protocols with input from the local community to ensure that a trial is acceptable. Research funders should require inclusive community engagement plans in all proposals and should collaborate with governments, national research institutions, and multilateral agencies at the start of an emergency to agree research priorities. Research ethics committees must consider “whether the proposed consent processes are the most appropriate and sensitive that they can be in the circumstances.”17 The urgency of a pandemic is never an excuse for poorly designed studies, ethical misconduct, or the violation of human rights.

Footnotes
Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following. GM-K has been involved in uncovering potentially fraudulent papers on ivermectin for covid-19. SW’s previous post-doctoral research centre received funding from the Arnold Foundation.

References
1. National Academies of Sciences, Engineering, and Medicine.
Integrating clinical research into epidemic response: the Ebola experience.National Academies Press, 2017.

2. London AJ, Kimmelman J
Against pandemic research exceptionalism. Science2020;368:476-7. doi:10.1126/science.abc1731 pmid:32327600

3. Rosendaal FR
Review of: "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial Gautret et al 2010, DOI:10.1016/j.ijantimicag.2020.105949. Int J Antimicrob Agents2020;56:106063. doi:10.1016/j.ijantimicag.2020.106063 pmid:32674928

4. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res2020;178:104787. doi:10.1016/j.antiviral.2020.104787 pmid:32251768

5. Bryant A, Lawrie TA, Dowswell T, et al
Ivermectin for prevention and treatment of COVID-19 infection: a systematic review, meta-analysis, and trial sequential analysis to inform clinical guidelines. Am J Ther2021;28:e434-60. doi:10.1097/MJT.0000000000001402 pmid:34145166

6. Hill A, Garratt A, Levi J, et al
Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection[Retracted]. Open Forum Infect Dis2021doi:10.1093/ofid/ofab358

7. Schraer R, Goodman J. Ivermectin: how false science created a covid “miracle” drug. BBC News 2021 Oct 6. https://www.bbc.co.uk/news/health-58170809
8. Hill A, Mirchandani M, Pilkington V
Ivermectin for COVID-19: addressing potential bias and medical fraud. Open Forum Infect Dis2022;9:b645. doi:10.1093/ofid/ofab645 pmid:35071686

9. Manu P
Expression of concern for Bryant A, Lawrie TA, Dowswell T, Fordham EJ, Mitchell S, Hill SR, Tham TC. Ivermectin for prevention and treatment of COVID-19 Infection: a systematic review, meta-analysis, and trial sequential analysis to inform clinical guidelines. Am J Ther2022;29:e232. doi:10.1097/CND.0000000000000400 pmid:35142702

10. Dyer O
. Covid-19: Mexico City gave ivermectin kits to people with covid in “unethical” experiment. BMJ2022;376:o453. doi:10.1136/bmj.o453 pmid:35193882

11. Cohen PN. SocArXiv Steering Committee. On withdrawing “Ivermectin and the odds of hospitalization due to COVID-19,” by Merino et al. SocArXiv 2022. https://socopen.org/2022/02/04/on-withdrawing-ivermectin-and-the-odds-of-hospitalization-due-to-covid-19-by-merino-et-al/
12. Political Constitution of the United States of Mexico. (1917, with reforms and additions through October of 2015), Institute of Legal Research, UNAM. https://www2.juridicas.unam.mx/constitucion-reordenada-consolidada/en/vigente
13. Popp M, Stegemann M, Metzendorf MI, et al
Ivermectin for preventing and treating COVID-19. Cochrane Database Syst Rev2021;7:CD015017.pmid:34318930

14. Horby P, Lim WS, Emberson JR, et al., RECOVERY Collaborative Group
Dexamethasone in hospitalized patients with COVID-19. N Engl J Med2021;384:693-704. doi:10.1056/NEJMoa2021436 pmid:32678530

15. Cao B, Wang Y, Wen D, et al
A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med2020;382:1787-99. doi:10.1056/NEJMoa2001282 pmid:32187464

16. University of Oxford. The recovery trial—two years on. 2022. https://www.ox.ac.uk/news/features/recovery-trial-two-years
17. Nuffield Council on Bioethics. Research in global health emergencies: ethical issues. 2020. https://www.nuffieldbioethics.org/publications/research-in-global-health-emergencies

LOOKING FOR TROUBLE [Science, 14 Apr 2022]

BYJON COHEN

Trapping bats with Supaporn Wacharapluesadee, who hunts for viruses to understand and prevent pandemic threats

In rural Thailand, an elephant sitting in the road is not a charming sight. The massive beasts have a penchant for ripping off bumpers, tusking doors, and sitting on hoods. So in January, when an elephant loomed on the pavement ahead, a van carrying a team of bat researchers on a road 200 kilometers southeast of Bangkok stopped abruptly. As the animal loped toward the van, ears flapping and trunk swinging, the driver slowly backed up. At last, the elephant lumbered back into the other lane and the driver crept past. “That was wild!” a member of the team said.

Its leader, Supaporn Wacharapluesadee, who stands out as mild mannered in a famously mild-mannered culture, fell off her seat laughing with relief. She is used to much smaller, but more consequential, menaces. Within hours, she and her team planned to be in Thailand’s Khao Ang Rue Nai Wildlife Sanctuary examining animals for dangerous viruses that might spill over into humans—or already have.

Supaporn is one of the world’s most accomplished virus hunters. She is known for her work tracking Nipah virus, a batborne pathogen that is less contagious than SARS-CoV-2 but more deadly to humans. She has found bat coronaviruses related to both SARS-CoV, which triggered the epidemic of sudden acute respiratory syndrome (SARS) nearly 2 decades ago, and the virus behind Middle East respiratory syndrome (MERS). And her quest has gained new importance during the COVID-19 pandemic, which likely originated when a bat coronavirus evolved into SARS-CoV-2 and crossed over into humans, perhaps through an intermediate host animal.

She was the first researcher to sequence SARS-CoV-2 outside China—not in an animal, but in an airline passenger—and she is on the trail of its wild relatives. From her base at Chulalongkorn University in Bangkok, Supaporn has made many forays like the one delayed by the elephant. Those outings added precious data points in the hunt for SARS-CoV-2’s origin as she identified bat coronaviruses on the virus’ family tree—some of which may be its closest relatives yet found.

The 52-year-old scientist’s career blossomed over the past decade after she joined PREDICT, a multicountry, well-funded epidemiological program sponsored by the U.S. Agency for International Development (USAID). Until it ended in 2019, the program looked for pathogens in animals and humans to spot new pandemic threats. The World Health Organization in fall 2021 named her a member of its new Scientific Advisory Group for the Origins of Novel Pathogens.

“She’s fabulous,” says Dennis Carroll, a tropical disease specialist who started PREDICT. “She’s demonstrated over the years a really innovative mind in terms of the fieldwork she does, and she’s extremely practical, doing really high-quality lab work.”

PREDICT’s principal investigator, epidemiologist Jonna Mazet of the University of California, Davis, also admires how Supaporn has made her way in a male-dominated field. “She’s had to fight for what she got, which is especially impressive in a country like Thailand, where the women are not as supported as they are here in the U.S.”

Yet some scientists—including Supaporn’s former boss, Thiravat Hemachudha—question whether the type of arduous wild animal surveillance she did on that elephant-interrupted January trip truly makes humans safer. “I don’t think it’s that valuable, and it may be dangerous,” says Thiravat, a neurologist who last year had a complicated falling out with Supaporn that has left her without lab equipment and staff.

Thiravat and other scientists contend that the most efficient way to head off new pandemics is to more aggressively test sick livestock and other animals in contact with people, as well as people with unexplained illnesses, and intensify surveillance of people who often interact with animals harboring dangerous pathogens. “Our motto is: Minimize budget and maximize benefit,” Thiravat says.

Supaporn, who hopes to take part in two new viral sleuthing efforts designed to derail spillovers, including a proposed multibillion-dollar Global Virome Project (GVP), says critics are presenting a false choice. To understand viral threats, she says, wildlife surveillance is as important as testing people and livestock. “If we don’t do anything, we will not know anything,” she says. She and other pathogen hunters say if earlier findings from wild animals had been taken more seriously, “coronavirus” would not have become a common word in every spoken language.

SUPAPORN’S PARENTS MADE fittings for jewelry, and as a child she thought she would become an artist like her brother. But as a teen she realized her talent lay in science. She earned an undergraduate degree in medical technology and spent 10 years working in several diagnostic labs. “When I was young, I was not a communicative person, so working in the lab, there was no need to talk to anyone,” Supaporn says. “I thought being a technician was the best job for me.”

But when a supervisor hired an outside company to solve an assay problem that she knew how to fix herself, she decided her tech days had ended. “I thought, ‘I can do more than that.’”
In graduate school, she studied with Thiravat, who treated people infected with rabies, mainly through dog bites. A related virus that infects Australian bats also causes a rabieslike disease in humans, so she and Thiravat decided in 2002 to start sampling bats in Thailand. The bats carried antibodies to that second virus, indicating its presence in Thailand as well. At the government’s behest, the researchers also began sampling bats and other animals for Nipah virus, which emerged in Malaysian pigs and their farmers in 1998, killing up to 75% of infected humans.

All in the family
Coronaviruses related to SARS-CoV-2 have turned up in Rhinolophus bats roosting all across Asia. Differences between viral sequences have enabled researchers to build a family tree and estimate that the closest relatives shared a common ancestor with the pandemic virus a decade ago. Supaporn Wacharapluesadee’s team found a virus in Thailand (No. 9) that shared a relative about 140 years ago and has identified but not yet published closer relatives.

Supaporn, Thiravat, and colleagues repeatedly found antibodies to Nipah in Pteropus, or flying foxes, the world’s largest bats with a 1.5-meter wingspan. Eventually, the team isolated the virus itself from a bat. To dispel folklore about a popular aphrodisiac in Thailand and other Asian countries, they published a paper in Clinical Infectious Diseases in 2006 with a startling title: “Drinking Bat Blood May Be Hazardous to Your Health.”

To prevent Nipah spillovers, for 2 decades Supaporn has tested humans and pigs in villages near Wat Luang Phrommawat, a 400-year-old temple with a grove of trees where some 10,000 flying foxes roost. She has never found Nipah virus or its immunological footprints in humans or pigs, but Supaporn says the work led the locals to discard fruit that was partially eaten, possibly by the bats.

“I have a responsibility to the community to do education about this risk,” she says.

The Nipah studies caught the attention of scientists at the EcoHealth Alliance, a conservation-oriented nonprofit in New York City that was part of PREDICT, and in 2009 it subcontracted with Supaporn to do wildlife surveillance in Thailand. Peter Daszak, who heads EcoHealth, notes that few researchers in the countries where pandemics tend to originate do such work.

“Supaporn’s one of those who gets it,” says Daszak, who has been scrutinized because of the possibility—dismissed by many scientists as pure speculation—that SARS-CoV-2 leaked from a lab EcoHealth collaborated with at the Wuhan Institute of Virology in China. “And it’s not easy for someone to develop their own pathway like she has.”

Since then, Supaporn has done multiple studies with EcoHealth and PREDICT. She showed that bat guano used as fertilizer by Thai farmers was contaminated with a coronavirus related to the cause of MERS, and she ranked the spillover potential of different animal viruses. Even before the pandemic, she had described 63 coronavirus sequences detected in 13 species of Thai bats she sampled.

Shi Zhengli, who runs the Wuhan lab and also has come under attack by lableak proponents, has collaborated with Supaporn and says they often swap ideas. “Tropical Asia is a hot spot of wildlife-borne emerging infectious diseases,” Shi says, “so her job is very important for disease prevention and precaution in the region.”

THE KINDS OF THREATS Supaporn had been tracking became catastrophically real at the beginning of 2020. On 8 January, a passenger arriving from Wuhan at Bangkok’s international airport registered hot on thermal scanning equipment. An ear check showed her temperature was 38.1°C. Rome Buathong, a field epidemiologist for the Thai Ministry of Public Health who had set up the scanners 5 days earlier when news arrived about the outbreak in Wuhan, promptly sent the woman to the hospital. All viral tests were negative, so Rome contacted Supaporn, who had worked with him years earlier to screen air passengers for Ebola and Zika viruses.

On 9 January—the day before Chinese researchers first publicly reported SARS-CoV-2’s genome—Supaporn discovered the genetic signature of a novel virus in that Wuhan visitor, becoming the first scientist outside China to do so. A database search showed the new virus was closest to a coronavirus in Chinese bats that Daszak and Shi had reported in 2017. “Ten years ago, no one thought bats were important—we thought only about influenza,” Rome says. “But Supaporn was very keen to do a lot with bats. Who knew?”

The COVID-19 pandemic in early 2020 halted field research globally, but Supaporn, with funding from the U.S. Department of Defense’s Biological Threat Reduction Program, managed that June to send a team to a large cave in western Thailand that is home to a few million bats. The endeavor was part of a general pathogen surveillance effort, but the group hoped to find a clue to SARS-CoV-2’s origin by sampling Rhinolophus bats, also known as horseshoe bats for the shape of their noses. The genus, comprising more than 100 species, is the main host for SARS-related coronaviruses.

Horseshoe bats live in small colonies that are often hard to find, and the cave didn’t yield any. But in a water pipe draining a reservoir that’s part of the Khao Ang Rue Nai Wildlife Sanctuary, Supaporn’s team trapped 100 Rhinolophus acuminatus. Rectal swabs from 13 tested positive for coronaviruses, including one described in Nature Communications on 9 February 2021.
Dubbed RacCS203, the virus was 91.5% identical in genetic sequence with SARS-CoV-2. That similarity implied a common ancestor from about 140 years ago, according to an analysis led by evolutionary biologists David Robertson and Spyros Lytras of the MRC-University of Glasgow Centre for Virus Research, published online on 8 February in Genome Biology and Evolution.

Other researchers found bat coronaviruses related to SARS-CoV-2 in China, Laos, Vietnam, Cambodia, and Japan. One virus from a colony in limestone caves in Laos was 96.8% similar in sequence to the human virus—perhaps a decade removed. Even it is too distant to offer anything more than crumbs on the evolutionary path that led to the pandemic virus. But Robertson is convinced that Asia’s bats harbor far closer relatives to SARS-CoV-2. “There’s definitely something that’s not been sampled,” he says.

On the trip this January, Supaporn returned to the sanctuary in search of closer matches. RacCS203, unlike the virus from Laos, does not infect by binding to the human cellular receptor favored by SARS-CoV-2. But antibodies in the blood of bats in the sanctuary powerfully neutralized the pandemic virus, suggesting they may have been infected with a coronavirus that uses that receptor, too.

Some researchers think the bat virus hunt will do little to clarify the pandemic’s origin. A distant bat precursor to SARS-CoV-2 might have spread long ago to an intermediate host—perhaps a rat, civet cat, raccoon dog, or pangolin, all known to host bat viruses—and evolved there for years before infecting humans. But Supaporn is betting she’ll find revealing clues in bats. “It would be good to fill in the gaps of the origin story in Southeast Asia because in Thailand alone there are 23 Rhinolophus species,” she says.

Filling in the gaps is a painstakingly slow, expensive, risky, and often hugely unpleasant process. “You’re looking for something rare, and you need a ton of samples to pick up the rare thing,” Mazet says.

BY THE TIME SUPAPORN’S van passed the elephant and joined the rest of the team at the field site, it was after 4 p.m. With military efficiency, the team—two dozen grad students, ecologists, and veterinarians—set up a lab on the ground floor of an abandoned traditional Thai house on stilts. The first order of business, ironically, was to protect the bats from human viruses, including SARS-CoV-2: Everyone had nasal swabs, which came back negative.

Next, team members put on hairnets, polyethylene coveralls, nitrile gloves, and N95 masks to protect themselves. The temperature was 32°C. Sweat soon soaked every bit of fabric under the zipped-up suits.

A half-dozen men, who also donned rubber boots and mining headlamps, left the lab and went down an adjacent road to the water pipe, home to a few hundred R. acuminatus. The group scuttled down a ladder to the pipe’s opening. Butterfly nets in hand, they hunched into the tunnel, where the stench of bat feces, urine, and wet fur parked in the nose. A mesh placed over the pipe’s opening caught any bats trying to leave the roost.

Emerging from the pipe, the men untangled the mouse-size bats from their nets, a delicate process given the tangle of spiny wings in the mesh and the animals’ ice pick teeth. Each bat went into its own cloth bag. Supaporn did not take part in the procedure. “I’m not good at it,” she says, noting that she has been bitten several times.

The next day, the team trapped another 50 Rhinolophus from the water pipe. The group also captured 50 bats of another species, Hipposideros, from beneath a botanical museum at the wildlife sanctuary, so they could be tested to see whether any coronaviruses had jumped from the Rhinolophus roosting nearby. After each trapping, Supaporn’s team took the animals back to the field station for measurements and tissue samples, aiming to free the bats as quickly as possible to minimize trauma and harm.

“They’re one of the more efficient teams I’ve worked with,” says Kevin Olival, an ecologist at EcoHealth. “In many other countries, it would take 5, 6, 7 days to get that many bats.”

The field station resembled a production line. At the first cluster of tables, team members weighed each bat, measured head and ear size with a caliper, shone a light through the wing to estimate age from bone joint size, measured wingspan, and tweezed off parasites, saving them in tiny tubes for a separate study. Station two swabbed the anus and mouth, hole punched tissue from a wing, aspirated blood from a capillary, and then brushed red nail polish on toes so no released bat would be sampled twice.

The swabs were later tested for viral genetic material and the wing tissue for DNA confirmation of the species. Supaporn and her collaborators in other countries will test the blood for antibodies against a wide range of paramyxoviruses, influenza viruses, filoviruses, and coronaviruses.

Supaporn worked at a third station, centrifuging bat blood to separate the plasma. She took an occasional breather to pluck a cloth bag from the end of the production line, smiling broadly each time she nudged out a bat with red nail polish and watched it fly off toward home.

Data from the January trapping, to Supaporn’s surprise, indicated coronaviruses unrelated to the SARS family in the Hipposideros but none in the Rhinolophus. Antibody analyses are still underway, and she suspects many Rhinolophus will test positive for past infections with SARS-related viruses.

Another foray, a March 2021 expedition to a cave west of Bangkok, yielded two new SARS-CoV-2–related coronaviruses in a species of Rhinolophus called R. pusillus. Supaporn analyzed them with Linfa Wang, a specialist in emerging infectious diseases at Duke-NUS Medical School in Singapore who in 2013 co-wrote a paper with Shi and Daszak describing the first bat coronavirus linked to SARS-CoV. Wang says he and Supaporn plan to report that in some parts of the viral surface protein that docks onto animal cells, the new viruses “have a closer relationship with SARS-CoV-2 than any other previously found in bats.”

HEROIC AS SUCH WILDLIFE surveillance may seem, some scientists question its value for heading off future pandemics.

PREDICT, which received $207 million from USAID from 2009 to 2019, discovered 959 novel viruses and identified hot spots for spillovers to humans, along with training Supaporn and nearly 7000 other researchers. “We were building their surveillance systems with them,” Mazet says.

Edward Holmes, an evolutionary biologist at the University of Sydney, applauds PREDICT’s training efforts but has doubts about whether the effort made the world safer. “It produced a fair amount of sequence data, but has it actually predicted anything?” he asks. “I don’t really know. It didn’t get SARS-CoV-2.”

Carroll, who retired from USAID in 2019, and scientists who participated in PREDICT contend that the project clarified what drives spillovers, such as the wildlife trade at markets and deforestation. PREDICT’s supporters also say it pinpointed sites where outbreaks are most likely. But Carroll readily acknowledges PREDICT’s limitations. “Its scope was too small to have a meaningful impact,” he says.

Hot zones
Researchers proposing a Global Virome Project have mapped regions where unknown viruses in wild mammals are most likely to spark human pandemics. Their predictions draw on data on known viruses, traits that predispose viruses to infecting humans, and human populations.
Although Southeast Asia has been a hot spot of outbreaks driven by bat viruses, the Amazon region’s pandemic potential may be much higher.

Carroll, Mazet, Daszak, and a small group of other researchers see PREDICT as a trial run for a much bigger effort: a GVP that aims to identify 75% of the viruses most likely to spill over within 10 years, at an estimated cost of $4 billion. GVP organizers, who started to flesh out the idea 6 years ago, had hoped to launch in 2020 with support from China and Thailand. The pandemic derailed their plans—but also underscored the need, Carroll, Supaporn, and other researchers argued last year in a commentary in The BMJ.

Holmes has assailed the idea of the GVP since it was first floated. “It’s absolute nonsense,” he says. “It’s too big a bloody arena.” Nearly all threatening pathogens are RNA viruses, which mutate at a fast clip, constantly creating new variants, Holmes notes. “You’ve got an amazing diversity of viruses that are continually turning over, so how would you then decide, ‘That’s the one that I’m worried about?’” he asks. “Surveillance is infinitely better and more cost-effectively directed at humans.”

Supaporn counters that the goal of wildlife surveillance isn’t to characterize every potential viral threat, but rather to learn how viruses evolve. And she is convinced that this work can predict the most likely future pathogens. “Even a general sense of this is extremely valuable to public health planning efforts,” she says. “Learn, understand, prepare.”

THOSE ARGUMENTS MAY HAVE contributed to Supaporn’s falling out with Thiravat, which forced her to walk away from the institution he heads, the Health Science Centre of the Thai Red Cross Emerging Infectious Diseases program at King Chulalongkorn Memorial Hospital.
She is now at its sister Clinical Centre, without her equipment and trained technicians. Work like Supaporn’s promises more risks than benefits, Thiravat contends. “Wildlife surveillance may introduce human pathogens to wildlife and vice versa.” As for SARS-CoV-2, he believes it was not a natural jump of a virus from animals to humans. “It was a product of lab leak of virus after manipulation,” he asserts. (Thiravat has also advocated using the antiparasitic drug ivermectin to treat COVID-19, even though multiple studies have shown it is ineffective.)

Thiravat contends that Supaporn siphoned off about $400,000 from grants. But an investigation conducted by the Thai Red Cross Society exonerated her in July 2021, concluding in a letter (which she supplied to Science) that there was “no evidence of financial conduct contrary to [her employer’s] regulations.”

Some Supaporn supporters say Thiravat is jealous of the attention she has received for her coronavirus work during the pandemic. She says the problem began when she challenged things he said to his supervisors, which she did not want to discuss in detail. “I’ve always respected him—he is my mentor and an intelligent clinician and scientist,” she says. “And I’m lucky that even though I have some politics in the lab, people outside Thailand don’t think that I’m wrong, and they support me.”

Supaporn’s setbacks mean she must now rely on colleagues, including Wang, to complete the lab analyses of samples her team collects in the field. But she’s upbeat about her future.
In early March, she met with researchers from a new $125 million, 5-year project launched last year by USAID called Discovery & Exploration of Emerging Pathogens—Viral Zoonoses (DEEP VZN), taking them to the flying fox colony in the trees at Wat Luang Phrommawat. While she waits to see whether DEEP VZN makes her a collaborator and whether the GVP finds funding, Supaporn has enough grant money to continue her fieldwork for the time being.

For now, she focuses on training students and embracing the many unknowns she faces. “It’s a Buddhist teaching,” she says. “Uncertainty is certainty.”

Which could also be a motto for the entire pandemic prevention enterprise.

LOOKING FOR TROUBLE Trapping bats with Supaporn Wacharapluesadee, who hunts for viruses to understand and prevent pandemic threats [Science, 14 Apr 2022]

BY JON COHEN

On the hunt for new viruses, this bat-trapping scientist hopes to prevent future pandemics

In rural Thailand, an elephant sitting in the road is not a charming sight. The massive beasts have a penchant for ripping off bumpers, tusking doors, and sitting on hoods. So in January, when an elephant loomed on the pavement ahead, a van carrying a team of bat researchers on a road 200 kilometers southeast of Bangkok stopped abruptly. As the animal loped toward the van, ears flapping and trunk swinging, the driver slowly backed up. At last, the elephant lumbered back into the other lane and the driver crept past. “That was wild!” a member of the team said.

Its leader, Supaporn Wacharapluesadee, who stands out as mild mannered in a famously mild-mannered culture, fell off her seat laughing with relief. She is used to much smaller, but more consequential, menaces. Within hours, she and her team planned to be in Thailand’s Khao Ang Rue Nai Wildlife Sanctuary examining animals for dangerous viruses that might spill over into humans—or already have.

Supaporn is one of the world’s most accomplished virus hunters. She is known for her work tracking Nipah virus, a batborne pathogen that is less contagious than SARS-CoV-2 but more deadly to humans. She has found bat coronaviruses related to both SARS-CoV, which triggered the epidemic of sudden acute respiratory syndrome (SARS) nearly 2 decades ago, and the virus behind Middle East respiratory syndrome (MERS). And her quest has gained new importance during the COVID-19 pandemic, which likely originated when a bat coronavirus evolved into SARS-CoV-2 and crossed over into humans, perhaps through an intermediate host animal.

She was the first researcher to sequence SARS-CoV-2 outside China—not in an animal, but in an airline passenger—and she is on the trail of its wild relatives. From her base at Chulalongkorn University in Bangkok, Supaporn has made many forays like the one delayed by the elephant. Those outings added precious data points in the hunt for SARS-CoV-2’s origin as she identified bat coronaviruses on the virus’ family tree—some of which may be its closest relatives yet found.

The 52-year-old scientist’s career blossomed over the past decade after she joined PREDICT, a multicountry, well-funded epidemiological program sponsored by the U.S. Agency for International Development (USAID). Until it ended in 2019, the program looked for pathogens in animals and humans to spot new pandemic threats. The World Health Organization in fall 2021 named her a member of its new Scientific Advisory Group for the Origins of Novel Pathogens.

“She’s fabulous,” says Dennis Carroll, a tropical disease specialist who started PREDICT. “She’s demonstrated over the years a really innovative mind in terms of the fieldwork she does, and she’s extremely practical, doing really high-quality lab work.”

PREDICT’s principal investigator, epidemiologist Jonna Mazet of the University of California, Davis, also admires how Supaporn has made her way in a male-dominated field. “She’s had to fight for what she got, which is especially impressive in a country like Thailand, where the women are not as supported as they are here in the U.S.”

Yet some scientists—including Supaporn’s former boss, Thiravat Hemachudha—question whether the type of arduous wild animal surveillance she did on that elephant-interrupted January trip truly makes humans safer. “I don’t think it’s that valuable, and it may be dangerous,” says Thiravat, a neurologist who last year had a complicated falling out with Supaporn that has left her without lab equipment and staff.

Thiravat and other scientists contend that the most efficient way to head off new pandemics is to more aggressively test sick livestock and other animals in contact with people, as well as people with unexplained illnesses, and intensify surveillance of people who often interact with animals harboring dangerous pathogens. “Our motto is: Minimize budget and maximize benefit,” Thiravat says.

Supaporn, who hopes to take part in two new viral sleuthing efforts designed to derail spillovers, including a proposed multibillion-dollar Global Virome Project (GVP), says critics are presenting a false choice. To understand viral threats, she says, wildlife surveillance is as important as testing people and livestock. “If we don’t do anything, we will not know anything,” she says. She and other pathogen hunters say if earlier findings from wild animals had been taken more seriously, “coronavirus” would not have become a common word in every spoken language.

SUPAPORN’S PARENTS MADE fittings for jewelry, and as a child she thought she would become an artist like her brother. But as a teen she realized her talent lay in science. She earned an undergraduate degree in medical technology and spent 10 years working in several diagnostic labs. “When I was young, I was not a communicative person, so working in the lab, there was no need to talk to anyone,” Supaporn says. “I thought being a technician was the best job for me.”

But when a supervisor hired an outside company to solve an assay problem that she knew how to fix herself, she decided her tech days had ended. “I thought, ‘I can do more than that.’”

In graduate school, she studied with Thiravat, who treated people infected with rabies, mainly through dog bites. A related virus that infects Australian bats also causes a rabieslike disease in humans, so she and Thiravat decided in 2002 to start sampling bats in Thailand. The bats carried antibodies to that second virus, indicating its presence in Thailand as well. At the government’s behest, the researchers also began sampling bats and other animals for Nipah virus, which emerged in Malaysian pigs and their farmers in 1998, killing up to 75% of infected humans.

All in the family
Coronaviruses related to SARS-CoV-2 have turned up in Rhinolophus bats roosting all across Asia. Differences between viral sequences have enabled researchers to build a family tree and estimate that the closest relatives shared a common ancestor with the pandemic virus a decade ago. Supaporn Wacharapluesadee’s team found a virus in Thailand (No. 9) that shared a relative about 140 years ago and has identified but not yet published closer relatives.

Supaporn, Thiravat, and colleagues repeatedly found antibodies to Nipah in Pteropus, or flying foxes, the world’s largest bats with a 1.5-meter wingspan. Eventually, the team isolated the virus itself from a bat. To dispel folklore about a popular aphrodisiac in Thailand and other Asian countries, they published a paper in Clinical Infectious Diseases in 2006 with a startling title: “Drinking Bat Blood May Be Hazardous to Your Health.”

To prevent Nipah spillovers, for 2 decades Supaporn has tested humans and pigs in villages near Wat Luang Phrommawat, a 400-year-old temple with a grove of trees where some 10,000 flying foxes roost. She has never found Nipah virus or its immunological footprints in humans or pigs, but Supaporn says the work led the locals to discard fruit that was partially eaten, possibly by the bats.

“I have a responsibility to the community to do education about this risk,” she says.

The Nipah studies caught the attention of scientists at the EcoHealth Alliance, a conservation-oriented nonprofit in New York City that was part of PREDICT, and in 2009 it subcontracted with Supaporn to do wildlife surveillance in Thailand. Peter Daszak, who heads EcoHealth, notes that few researchers in the countries where pandemics tend to originate do such work.

“Supaporn’s one of those who gets it,” says Daszak, who has been scrutinized because of the possibility—dismissed by many scientists as pure speculation—that SARS-CoV-2 leaked from a lab EcoHealth collaborated with at the Wuhan Institute of Virology in China. “And it’s not easy for someone to develop their own pathway like she has.”

Since then, Supaporn has done multiple studies with EcoHealth and PREDICT. She showed that bat guano used as fertilizer by Thai farmers was contaminated with a coronavirus related to the cause of MERS, and she ranked the spillover potential of different animal viruses. Even before the pandemic, she had described 63 coronavirus sequences detected in 13 species of Thai bats she sampled.

Shi Zhengli, who runs the Wuhan lab and also has come under attack by lableak proponents, has collaborated with Supaporn and says they often swap ideas. “Tropical Asia is a hot spot of wildlife-borne emerging infectious diseases,” Shi says, “so her job is very important for disease prevention and precaution in the region.”

THE KINDS OF THREATS Supaporn had been tracking became catastrophically real at the beginning of 2020. On 8 January, a passenger arriving from Wuhan at Bangkok’s international airport registered hot on thermal scanning equipment. An ear check showed her temperature was 38.1°C. Rome Buathong, a field epidemiologist for the Thai Ministry of Public Health who had set up the scanners 5 days earlier when news arrived about the outbreak in Wuhan, promptly sent the woman to the hospital. All viral tests were negative, so Rome contacted Supaporn, who had worked with him years earlier to screen air passengers for Ebola and Zika viruses.

On 9 January—the day before Chinese researchers first publicly reported SARS-CoV-2’s genome—Supaporn discovered the genetic signature of a novel virus in that Wuhan visitor, becoming the first scientist outside China to do so. A database search showed the new virus was closest to a coronavirus in Chinese bats that Daszak and Shi had reported in 2017. “Ten years ago, no one thought bats were important—we thought only about influenza,” Rome says.
“But Supaporn was very keen to do a lot with bats. Who knew?”
The COVID-19 pandemic in early 2020 halted field research globally, but Supaporn, with funding from the U.S. Department of Defense’s Biological Threat Reduction Program, managed that June to send a team to a large cave in western Thailand that is home to a few million bats.

The endeavor was part of a general pathogen surveillance effort, but the group hoped to find a clue to SARS-CoV-2’s origin by sampling Rhinolophus bats, also known as horseshoe bats for the shape of their noses. The genus, comprising more than 100 species, is the main host for SARS-related coronaviruses.

Horseshoe bats live in small colonies that are often hard to find, and the cave didn’t yield any.
But in a water pipe draining a reservoir that’s part of the Khao Ang Rue Nai Wildlife Sanctuary, Supaporn’s team trapped 100 Rhinolophus acuminatus. Rectal swabs from 13 tested positive for coronaviruses, including one described in Nature Communications on 9 February 2021.
Dubbed RacCS203, the virus was 91.5% identical in genetic sequence with SARS-CoV-2. That similarity implied a common ancestor from about 140 years ago, according to an analysis led by evolutionary biologists David Robertson and Spyros Lytras of the MRC-University of Glasgow Centre for Virus Research, published online on 8 February in Genome Biology and Evolution.

Other researchers found bat coronaviruses related to SARS-CoV-2 in China, Laos, Vietnam, Cambodia, and Japan. One virus from a colony in limestone caves in Laos was 96.8% similar in sequence to the human virus—perhaps a decade removed. Even it is too distant to offer anything more than crumbs on the evolutionary path that led to the pandemic virus. But Robertson is convinced that Asia’s bats harbor far closer relatives to SARS-CoV-2. “There’s definitely something that’s not been sampled,” he says.

On the trip this January, Supaporn returned to the sanctuary in search of closer matches. RacCS203, unlike the virus from Laos, does not infect by binding to the human cellular receptor favored by SARS-CoV-2. But antibodies in the blood of bats in the sanctuary powerfully neutralized the pandemic virus, suggesting they may have been infected with a coronavirus that uses that receptor, too.

Some researchers think the bat virus hunt will do little to clarify the pandemic’s origin. A distant bat precursor to SARS-CoV-2 might have spread long ago to an intermediate host—perhaps a rat, civet cat, raccoon dog, or pangolin, all known to host bat viruses—and evolved there for years before infecting humans. But Supaporn is betting she’ll find revealing clues in bats. “It would be good to fill in the gaps of the origin story in Southeast Asia because in Thailand alone there are 23 Rhinolophus species,” she says.

Filling in the gaps is a painstakingly slow, expensive, risky, and often hugely unpleasant process. “You’re looking for something rare, and you need a ton of samples to pick up the rare thing,” Mazet says.

BY THE TIME SUPAPORN’S van passed the elephant and joined the rest of the team at the field site, it was after 4 p.m. With military efficiency, the team—two dozen grad students, ecologists, and veterinarians—set up a lab on the ground floor of an abandoned traditional Thai house on stilts. The first order of business, ironically, was to protect the bats from human viruses, including SARS-CoV-2: Everyone had nasal swabs, which came back negative.

Next, team members put on hairnets, polyethylene coveralls, nitrile gloves, and N95 masks to protect themselves. The temperature was 32°C. Sweat soon soaked every bit of fabric under the zipped-up suits.

A half-dozen men, who also donned rubber boots and mining headlamps, left the lab and went down an adjacent road to the water pipe, home to a few hundred R. acuminatus. The group scuttled down a ladder to the pipe’s opening. Butterfly nets in hand, they hunched into the tunnel, where the stench of bat feces, urine, and wet fur parked in the nose. A mesh placed over the pipe’s opening caught any bats trying to leave the roost.

Emerging from the pipe, the men untangled the mouse-size bats from their nets, a delicate process given the tangle of spiny wings in the mesh and the animals’ ice pick teeth. Each bat went into its own cloth bag. Supaporn did not take part in the procedure. “I’m not good at it,” she says, noting that she has been bitten several times.

The next day, the team trapped another 50 Rhinolophus from the water pipe. The group also captured 50 bats of another species, Hipposideros, from beneath a botanical museum at the wildlife sanctuary, so they could be tested to see whether any coronaviruses had jumped from the Rhinolophus roosting nearby. After each trapping, Supaporn’s team took the animals back to the field station for measurements and tissue samples, aiming to free the bats as quickly as possible to minimize trauma and harm.

“They’re one of the more efficient teams I’ve worked with,” says Kevin Olival, an ecologist at EcoHealth. “In many other countries, it would take 5, 6, 7 days to get that many bats.”

The field station resembled a production line. At the first cluster of tables, team members weighed each bat, measured head and ear size with a caliper, shone a light through the wing to estimate age from bone joint size, measured wingspan, and tweezed off parasites, saving them in tiny tubes for a separate study. Station two swabbed the anus and mouth, hole punched tissue from a wing, aspirated blood from a capillary, and then brushed red nail polish on toes so no released bat would be sampled twice.

The swabs were later tested for viral genetic material and the wing tissue for DNA confirmation of the species. Supaporn and her collaborators in other countries will test the blood for antibodies against a wide range of paramyxoviruses, influenza viruses, filoviruses, and coronaviruses.

Supaporn worked at a third station, centrifuging bat blood to separate the plasma. She took an occasional breather to pluck a cloth bag from the end of the production line, smiling broadly each time she nudged out a bat with red nail polish and watched it fly off toward home.

Data from the January trapping, to Supaporn’s surprise, indicated coronaviruses unrelated to the SARS family in the Hipposideros but none in the Rhinolophus. Antibody analyses are still underway, and she suspects many Rhinolophus will test positive for past infections with SARS-related viruses.

Another foray, a March 2021 expedition to a cave west of Bangkok, yielded two new SARS-CoV-2–related coronaviruses in a species of Rhinolophus called R. pusillus. Supaporn analyzed them with Linfa Wang, a specialist in emerging infectious diseases at Duke-NUS Medical School in Singapore who in 2013 co-wrote a paper with Shi and Daszak describing the first bat coronavirus linked to SARS-CoV. Wang says he and Supaporn plan to report that in some parts of the viral surface protein that docks onto animal cells, the new viruses “have a closer relationship with SARS-CoV-2 than any other previously found in bats.”

HEROIC AS SUCH WILDLIFE surveillance may seem, some scientists question its value for heading off future pandemics.

PREDICT, which received $207 million from USAID from 2009 to 2019, discovered 959 novel viruses and identified hot spots for spillovers to humans, along with training Supaporn and nearly 7000 other researchers. “We were building their surveillance systems with them,” Mazet says.

Edward Holmes, an evolutionary biologist at the University of Sydney, applauds PREDICT’s training efforts but has doubts about whether the effort made the world safer. “It produced a fair amount of sequence data, but has it actually predicted anything?” he asks. “I don’t really know. It didn’t get SARS-CoV-2.”

Carroll, who retired from USAID in 2019, and scientists who participated in PREDICT contend that the project clarified what drives spillovers, such as the wildlife trade at markets and deforestation. PREDICT’s supporters also say it pinpointed sites where outbreaks are most likely. But Carroll readily acknowledges PREDICT’s limitations. “Its scope was too small to have a meaningful impact,” he says.

Hot zones
Researchers proposing a Global Virome Project have mapped regions where unknown viruses in wild mammals are most likely to spark human pandemics. Their predictions draw on data on known viruses, traits that predispose viruses to infecting humans, and human populations.

Although Southeast Asia has been a hot spot of outbreaks driven by bat viruses, the Amazon region’s pandemic potential may be much higher.

Carroll, Mazet, Daszak, and a small group of other researchers see PREDICT as a trial run for a much bigger effort: a GVP that aims to identify 75% of the viruses most likely to spill over within 10 years, at an estimated cost of $4 billion. GVP organizers, who started to flesh out the idea 6 years ago, had hoped to launch in 2020 with support from China and Thailand. The pandemic derailed their plans—but also underscored the need, Carroll, Supaporn, and other researchers argued last year in a commentary in The BMJ.

Holmes has assailed the idea of the GVP since it was first floated. “It’s absolute nonsense,” he says. “It’s too big a bloody arena.” Nearly all threatening pathogens are RNA viruses, which mutate at a fast clip, constantly creating new variants, Holmes notes. “You’ve got an amazing diversity of viruses that are continually turning over, so how would you then decide, ‘That’s the one that I’m worried about?’” he asks. “Surveillance is infinitely better and more cost-effectively directed at humans.”

Supaporn counters that the goal of wildlife surveillance isn’t to characterize every potential viral threat, but rather to learn how viruses evolve. And she is convinced that this work can predict the most likely future pathogens. “Even a general sense of this is extremely valuable to public health planning efforts,” she says. “Learn, understand, prepare.”

THOSE ARGUMENTS MAY HAVE contributed to Supaporn’s falling out with Thiravat, which forced her to walk away from the institution he heads, the Health Science Centre of the Thai Red Cross Emerging Infectious Diseases program at King Chulalongkorn Memorial Hospital.
She is now at its sister Clinical Centre, without her equipment and trained technicians. Work like Supaporn’s promises more risks than benefits, Thiravat contends. “Wildlife surveillance may introduce human pathogens to wildlife and vice versa.” As for SARS-CoV-2, he believes it was not a natural jump of a virus from animals to humans. “It was a product of lab leak of virus after manipulation,” he asserts. (Thiravat has also advocated using the antiparasitic drug ivermectin to treat COVID-19, even though multiple studies have shown it is ineffective.)

Thiravat contends that Supaporn siphoned off about $400,000 from grants. But an investigation conducted by the Thai Red Cross Society exonerated her in July 2021, concluding in a letter (which she supplied to Science) that there was “no evidence of financial conduct contrary to [her employer’s] regulations.”

Some Supaporn supporters say Thiravat is jealous of the attention she has received for her coronavirus work during the pandemic. She says the problem began when she challenged things he said to his supervisors, which she did not want to discuss in detail. “I’ve always respected him—he is my mentor and an intelligent clinician and scientist,” she says. “And I’m lucky that even though I have some politics in the lab, people outside Thailand don’t think that I’m wrong, and they support me.”

Supaporn’s setbacks mean she must now rely on colleagues, including Wang, to complete the lab analyses of samples her team collects in the field. But she’s upbeat about her future.

In early March, she met with researchers from a new $125 million, 5-year project launched last year by USAID called Discovery & Exploration of Emerging Pathogens—Viral Zoonoses (DEEP VZN), taking them to the flying fox colony in the trees at Wat Luang Phrommawat. While she waits to see whether DEEP VZN makes her a collaborator and whether the GVP finds funding, Supaporn has enough grant money to continue her fieldwork for the time being.

For now, she focuses on training students and embracing the many unknowns she faces. “It’s a Buddhist teaching,” she says. “Uncertainty is certainty.”

Which could also be a motto for the entire pandemic prevention enterprise.

New Coronavirus News from 6 Apr 2022

Medpage Today COVID Origins and EcoHealth Alliance; Malone Didn't Invent mRNA Vaccines LOOKING FOR TROUBLE [Medpage Today, 6 Apr 2022]

by Kristina Fiore

Welcome to the latest edition of Investigative Roundup, highlighting some of the best investigative reporting on healthcare each week.

The Nonprofit at the Center of the COVID Origin Debate
Vanity Fair's Katherine Eban details the evolution of the EcoHealth Alliance, the American non-profit with extensive ties to the Wuhan Institute of Virology that has fueled fires favoring a lab-leak origin for COVID-19.

The organization went from a struggling nonprofit focused on saving manatees (under the name Wildlife Trust) to winning multi-million-dollar federal grants to study pandemic prevention.

Its first big break came in 2009 when it won $18 million as part of a USAID pandemic prevention effort called PREDICT. But its leader, Peter Daszak, PhD, had been collaborating for years prior to that with Shi Zhengli, PhD, of the Wuhan Institute of Virology (WIV).

Daszak and Zhengli published their first paper together in 2005 -- on how horseshoe bats were a likely reservoir for SARS-like viruses. EcoHealth Alliance subcontracted $1.1 million of the PREDICT grant to WIV, Vanity Fair reported.

Eban details the work spawned by this alliance that has sparked several flash points in the SARS-CoV-2 origin debate. "Gain-of-function" research conducted in 2015 by Zhengli and collaborator Ralph Baric, PhD, of the University of North Carolina at Chapel Hill, involved the creation of two chimeric coronaviruses that were similar to the one that caused the 2002 SARS outbreak. One of those viruses was able to directly infect human cells, Vanity Fair reported.

In pursuit of securing future funding, EcoHealth Alliance also pitched the Defense Advanced Research Projects Agency (DARPA), which was seeking proposals for another pandemic prevention effort, called PREEMPT. The group wanted to examine SARS-like bat coronaviruses for furin cleavage sites and possibly insert new ones that would enable them to infect human cells. Vanity Fair noted that SARS-CoV-2 is notable for having a unique furin cleavage site that has led some scientists to consider whether the virus emerged from a lab. (DARPA rejected the proposal.)

Eban also details what appears to be concerted efforts by scientists to dismiss a lab-leak theory early in the pandemic.

On Feb. 1, 2020, NIAID Director Anthony Fauci, MD, emailed his deputy director Hugh Auchincloss, MD, with a subject line of "IMPORTANT," attaching the 2015 Baric and Zhengli paper. Later that day, Fauci joined a call, convened by Jeremy Farrar, director of the U.K.'s Wellcome Trust, that included a limited group of other top scientists including then-director of the NIH Francis Collins, MD, PhD, Kristian Andersen, PhD, and Robert Garry, PhD.

Over the next 4 days via email, the scientists scrutinized SARS-CoV-2's genetic sequence, paying special attention to the furin cleavage site. Initially, Andersen, Garry, and others found it "inconsistent with expectations from evolutionary theory." However, within a few days, four of the scientists who were on that call shared with Fauci the draft of a letter that argued a lab-leak theory was unlikely. It was published March 17, 2020 in Nature Medicine.

About a month before that, The Lancet published a statement from 26 scientists condemning "conspiracy theories" that COVID-19 doesn't have a natural origin. Daszak played a key role in organizing that paper, Vanity Fair reported.

Simon Wain-Hobson, PhD, of the Pasteur Institute in Paris, who has criticized gain-of-function research, told Vanity Fair that the group of scientists pushing the claim of natural origin "want to show that virology is not responsible [for causing the pandemic]. That is their agenda."

Malone Didn't Invent mRNA Vax
Robert Malone, MD, has become one of the loudest voices among physicians who spread COVID misinformation, buoyed by the claim he invented the mRNA vaccines -- but that claim is far from the truth, the New York Times reported.

The Times spent 2 days interviewing Malone at his 50-acre horse farm in Madison, Virginia -- about 2 hours southwest of Washington, D.C. -- where he was busy with appearances on conservative media, including Fox News and One America News.

He frequently uses his "inventor" status to question the safety of the mRNA vaccines, but COVID-19 experts, including three researchers who worked closely with Malone, told the Times his role was minimal at best.

Malone earned a medical degree from Northwestern University in 1991, and subsequently taught pathology at the University of California Davis and the University of Maryland over the next decade, before turning to biotech start-ups and consulting, the Times reported.

Malone did do work showing human cells could absorb RNA and produce proteins from it, as evidenced by a 1990 paper. But Malone was not the lead author, and at the time it wasn't known how to protect the genetic particles against immune system attack.

A co-author on that paper, Gyula Acsadi, MD, PhD, said none of the other authors would claim they had invented the mRNA vaccine, based on that paper.

"Some of his work was important, but that's a long way away from claiming to have invented the technology that underpins the vaccines as we use them today," Alastair McAlpine, MD, a pediatric infectious disease physician in Vancouver, told the Times.

The vaccines "are the result of hundreds of scientists all over the world, all combining to come together to form this vaccine," McAlpine said. "It was not one individual or the pioneering work of an individual person."

Valisure Wrongfully Investigated?
An FDA investigation into Valisure -- the upstart company that has detected carcinogens in several drugs and consumer products, leading to major recalls -- is dragging on and may be irrelevant, according to Consumer Reports.

About 7 months ago, the agency spent several weeks combing through Valisure's lab facilities and accused it of operating without proper regulatory approvals, Consumer Reports found.

The agency believes Valisure conducts tests for companies seeking FDA approval, but Valisure CEO David Light told Consumer Reports his company doesn't do that type of regulatory work.
Light added that the FDA has not communicated with him since that inspection.

Consumer Reports was able to obtain a copy of the 56-page inspection report, even though such reports are only supposed to be available when inspections are complete. (A FOIA officer subsequently realized the investigation was still open and asked Consumer Reports to destroy its copy.)

The inspection report held no evidence to support allegations that Valisure is doing preapproval testing for manufacturers, according to Consumer Reports.

Meanwhile, manufacturers of products that were recalled used the FDA investigation to undermine lawsuits brought by consumers who purchased goods implicated by Valisure's testing, the article states. It's not clear how manufacturers cited in the lawsuits found out about FDA's inspection of Valisure, as open investigations are confidential, Consumer Reports noted.

Valisure appeared on the scene in 2019 after discovering dimethylformamide in the blood pressure medication valsartan. Later that year, it revealed N-nitrosodimethylamine in the heartburn drug ranitidine. Last year, Valisure detected benzene in hand sanitizers, and then in several sunscreen sprays, and finally, in deodorants.

Americas at risk of further COVID-19 wave as cases surge in other regions, PAHO Director warns [Pan American Health Organization, 6 Apr 2022]

Washington D.C. 6 April 2022 (PAHO) – As cases of COVID-19 surge in Europe and East Asia due to Omicron BA.2, the Pan American Health Organization (PAHO) Director Carissa F. Etienne has urged countries to remain vigilant and urgently close vaccination gaps.

While COVID cases and deaths have dropped across much of the region, countries have reported more than 620,000 new cases each week. And in parts of North America and the Caribbean, where Omicron is becoming the predominant variant, new infections are beginning to rise.

With Omicron BA.2 already detected in 8.7% of sequences reported from South America, “time and time again, we’ve seen how the infection dynamics in Europe are mirrored here just a few weeks later,” the Director said in a media briefing today.

“We cannot ignore the risk of further COVID-19 surges,” she added. But we now “know what it takes to protect our people.”

However, with 240 million people in the Americas yet to receive a single shot of COVID-19 vaccine, vaccination gaps “will keep our region at risk during future waves.”

While more than 685 million people in the region have completed their COVID vaccination schedules, and 50 countries and territories have already begun to deliver booster doses, we must now “redouble our efforts to ensure that our vulnerable populations receive the doses they need,” as soon as possible, Dr. Etienne said.

The PAHO Director also urged countries to keep testing capacity in place “so we do not go into this next wave blind,” and have the full picture of Omicron BA.2 in the region.

“This means making tests easily accessible for everyone everywhere, to prevent new outbreaks and to prepare our health systems if cases surge,” she added.

Dr. Etienne also warned that some countries and territories have scaled back public health measures prematurely, highlighting that data “is our eyes and ears into this pandemic.”

“Just as we did before, we must adjust our strategies when cases rise, to save lives.”

With countries due to mark World Health Day on the 7th April under the theme “Our Planet, Our Health”, the PAHO Director also highlighted the urgent need for countries to work together towards a healthier, more sustainable future.

With an increase in temperatures, air pollution and extreme weather events, “it is undeniable that climate change has presented significant threats to our region’s health,” the Director said.
Health systems are also under threat as many hospitals were build in places vulnerable to floods, hurricanes, landslides and other extreme events.

“We are working to address this throughout the Region, but we all need to move faster,” added Dr. Etienne.

“Health system resilience is not just a necessity to overcome COVID, it is an investment for our future.”

SARS-CoV-2 transmission from human to free-roaming dogs during a severe COVID-19 outbreak in the Amazonian Region of Ecuador [News Medical, 6 Apr 2022]

By Dr. Liji Thomas

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that led to the devastating pandemic of coronavirus disease 2019 (COVID-19) has been found in remote jungles and humming urban centers alike. As efforts are on to stop the outbreak, using vaccines and public health interventions, the risk of spillover from wild mammals infected by the virus and living near humans is significant and may cause another epidemic as immunity wanes.

A new study shows how free-roaming village dogs in an Ecuadorian village within the Amazon jungle have been infected with the virus, presumably by the human hosts. The discovery of such infections and their ramifications are discussed in some detail.

Introduction
COVID-19 is primarily a zoonotic disease, presumed to have arisen from a bat coronavirus through an unidentified intermediate host. Now that the virus has spread widely throughout the world, it may spread in the reverse direction to animals; a phenomenon called zooanthroponosis. Dogs, cats, ferrets, hamsters, and such pet animals were screened for the infection early on.

This showed that dogs are relatively resistant to the virus compared to cats. However, numerous instances of dog and cat infections have been reported worldwide. Most such cases involved household dogs, ignoring the real problem of free-roaming dogs and cats that are found in large numbers in low- and middle-income countries, whether in city streets or in rural communities.

The current study, which appears in the journal One Health, deals with such a scenario.

What did the study show?
In this study, three free-roaming dogs in a small indigenous community that showed a high incidence of COVID-19 were infected with SARS-CoV-2, probably from humans. The isolation of the community means that it can be reached only from the air. The three dogs were fed collectively by the community.

The nasal and oral swabs from these three dogs, all adult males, were positive for the virus by the reverse transcriptase polymerase chain reaction (RT-PCR) test for viral ribonucleic acid (RNA). None of the dogs had symptomatic illness, but two or more viral nucleocapsid gene targets tested positive in all three. Two tested positive for the ORF1ab gene and one for the spike gene.

However, the cycle threshold (Ct) values were high in all three cases. Genomic sequencing could not be done, presumably because of the high Ct values.

The infection rate in the human community was 87%, with seven people having very high viral loads, over 108 copies/mL.

What are the implications?
In a heavily infected human community with free-roaming dogs, this initial report of human-to-dog transmission is the first anywhere in the world. Earlier, however, reports demonstrated that pet cats and dogs were readily infected with the virus by infected humans in the same or neighboring households.

The testing occurred as part of the surveillance program being carried out in indigenous communities in the Amazon region in Ecuador. Despite the absence of any symptoms of COVID-19, all three dogs in the village were infected. These dogs are part of the village’s food gathering and hunting activities and receive petting and food from all the community members indiscriminately.

The presence of seven heavily infected individuals within the community would account for the spread of the virus to the dogs, or at least to one of them, following which the dogs might well have spread it among themselves. The absence of the spike gene in two of the dogs could be due to the low viral loads, the same reason for the failure of genome sequencing.

Dogs have not been considered a likely source of SARS-CoV-2 transmission, but this is based on studies of pet animals from rich countries, where the number of free-roaming dogs is relatively low. In the different scenarios of developing and underdeveloped countries, the large number of dogs roaming the street could lead to such spread to other dogs, other companion animals, wild animals, and even humans.

The detection of the infection in these dogs is attributable to the sample collection simultaneous with the human outbreak. In earlier surveillance programs involving companion animals, samples from the latter were collected ten or more days after the first positive test in the animal owner.

The Amazon hosts a number of endangered species, and these may be further threatened by the rapid spread of COVID-19 among them. The Ecuadorian capuchin, which faces extinction in the near future under current circumstances, lives in the area that houses the community of this study.

Further research will be needed to elucidate the actual role of free-roaming and wild cats and dogs in the transmission of the virus and the infective period for animals following a diagnosis of COVID-19 in humans. This is crucial in understanding whether wild mammals can harbor the virus, leading to new forms of disease as well as creating unknown reservoirs of the virus.

Journal reference:
• Zambrano-Mila, M. et al. (2022) "SARS-CoV-2 infection in free roaming dogs from the Amazonian jungle", One Health, p. 100387. doi: 10.1016/j.onehlt.2022.100387. https://www.sciencedirect.com/science/article/pii/S2352771422000192

France reports over 200K Covid-19 cases as presidential polls approach [Business Standard, 6 Apr 2022]

France has reported 203,021 new Covid-19 cases in the past 24 hours, as the country prepares for the presidential elections on Sunday

France has reported 203,021 new Covid-19 cases in the past 24 hours, as the country prepares for the presidential elections on Sunday.

According to the French public health agency, 23,010 Covid-19 patients are currently hospitalised with 1,552 in intensive care. The agency also reported on Tuesday 140 additional Covid-19-related deaths in hospitals.

The application CovidTracker reported an increase in infections of 18.2 per cent in one week, with an average of 139,967 new daily cases reported between March 25 and 31, Xinhua news agency reported.

The application also reported an 8 per cent increase in the number of hospitalisations between March 25 and 31, with an increase of 3.6 per cent in intensive care admissions. Meanwhile, the number of daily deaths increased by 5.8 per cent.

According to the public health agency, 80.9 per cent of the French population has received at least one vaccine dose, and 79.5 per cent has been fully vaccinated.

France has lifted all Covid-19 restrictions. However, Morgane Bomsel, Research Director of the French National Center for Scientific Research, told French daily news BFMTV that "the pandemic is not over".

In the run-up to the presidential elections, the French Interior Ministry last week laid out health protocol for polling stations.

The vaccine pass or a negative Covid-19 test result will not be required to enter. However, while the wearing of masks and social distancing will not be mandatory, masks are recommended for the elderly, vulnerable and those who have tested positive for Covid-19.

COVID-19: Joint statement from ECDC and EMA on the administration of a fourth dose of mRNA vaccines [Europa.eu, 6 Apr 2022]

EMA’s COVID-19 task force (ETF) and the European Centre for Disease Prevention and Control (ECDC) have reviewed currently available studies and epidemiological data to provide a common position for EU/EEA countries on the current need and potential benefit of a fourth dose (second booster dose) of mRNA COVID-19 vaccines.

This statement is based on the currently available scientific evidence and, as such, is preliminary and may be subject to change as more data become available. This statement should not be interpreted as a regulatory decision in terms of changes to the product information. National recommendations regarding COVID-19 vaccines policies are made by National Immunisation Technical Advisory Groups.

Administration of a fourth dose of mRNA vaccines to immunocompromised individuals whose immune system may have mounted a suboptimal response to earlier vaccination is already recommended and should be part of current vaccination campaigns. There are currently no data on immunogenicity, safety or effectiveness of additional further doses in this population.
Additionally, in severely immunocompromised subjects, passive immunisation with monoclonal antibodies should be considered as an additional shield to protect against infection and disease.

The main source of empirical evidence on the potential public health impact of a fourth dose of mRNA vaccines as a second booster in immunocompetent individuals comes from data from Israel. These data indicate that a fourth dose of an mRNA vaccine given to immunocompetent individuals at least 4 months after the third dose is able to restore humoral immunity to the level seen after the third dose without raising any new safety concerns.
Immunogenicity data are available for a follow-up period of 3 weeks. No longer-term data are available on the duration of the achieved antibody levels however available data indicate that protection against Omicron infection may wane at a similar rate to that observed following the receipt of a third dose. Only preliminary data from Israel with respect to vaccine effectiveness against severe disease following a fourth dose are currently available.

There are currently no data with respect to a second booster dose of an mRNA vaccines in people who have received a primary series with another type of vaccine, e.g. a viral vector vaccine.

Although data on the rate of waning protection among the very elderly (adults above 80 years of age) following the first booster dose are still limited, due to the fragility of this population, the lower immune response to vaccination and the higher risk of severe COVID-19 a second booster could be administered. Data on safety and efficacy are only available for a fourth dose administered at least 4 months after a third dose, and this interval, together with local epidemiological data, should be taken into account when deciding on vaccination strategies.

In the context of continued high SARS-CoV-2 incidence, rates of severe outcomes and deaths remain low. For immunocompetent individuals between 60 and 80 years of age, there are currently no clear epidemiological signals from the European region of substantial waning of vaccine protection against severe COVID-19. Therefore there is no indication of an imminent need for a second booster dose in this population. However, continued close epidemiological and vaccine effectiveness monitoring is essential in order to rapidly detect signals indicating the emergence of an increasing risk of severe COVID-19 among vaccinated individuals. If such signals emerge, a fourth dose may be considered for adults between the ages of 60 and 80 years. Furthermore, local data on the epidemiological profile of severe COVID-19 cases may warrant a tailored use of a second booster dose in population groups identified as being at particular risk. If made available, vaccines adapted to better match recently circulating variants would be in principle preferable for additional boosters.

For immunocompetent individuals below 60 years of age, the administration of a second booster dose is not supported by the available data on continued level of vaccine protection against severe disease or death.

While seasonality is not yet established for SARS-COV-2, it is known that respiratory viruses tend to spread more consistently during the cold season. Therefore, plans for catch-up and re-vaccination campaigns should take this into account. In addition, in view of the possibility of new variants of concern (VOCs) emerging rapidly, the need to increase immunological breadth from available vaccines is a priority warranting the investigation of updated vaccine composition. However, it is still unclear when data on such updated vaccines will be available for a possible approval during the summer. Depending on whether waning protection against severe outcomes is observed in the coming months and on the evolving epidemiological situation, additional booster doses in anticipation of future waves or in advance of the next autumn/winter season may be needed in some or all age groups. Such additional doses will be of greatest value if administered closer to expected periods of increased viral circulation.

It must also be emphasized that, based on current evidence from longitudinal studies, routine surveillance and observational vaccine effectiveness studies, a primary course of vaccination remains the most efficient way to limit the disease burden and impact of COVID-19. COVID-19 vaccines continue to be very protective against severe disease, hospitalisation and death after completion of primary series and administration of the first booster dose. With vaccine uptake stagnating and in view of the significant variation in uptake across countries (only 63.5% of subjects aged 18 years and above in EU/EEA countries had received the first booster as of the end of March 2022), additional efforts are needed to increase vaccination uptake with a focus on the first booster dose as a public health priority.

ECDC and EMA will continue to closely follow vaccine effectiveness and epidemiological data, along with the progress in the development of adapted vaccines and will update advice accordingly. In addition, as more data are generated and submitted by marketing authorisation holders, these data may be reflected in the relevant product information where applicable.

The data and scientific evidence providing the basis for this statement are provided in the Annex.

Annex: Supporting rationale
Current epidemiological context
• Elevated COVID-19 incidence is resulting in a high proportion of reported hospitalisations and deaths among people with, but not necessarily due to, COVID-19. It is difficult to quantify this proportion which is likely to change over time with disease incidence. ECDC therefore considers ICU occupancy and ICU admissions to be the most reliable indicators of severity in the current context and the most stable over time.

• Many countries reported their highest case notification rates between January and February 2022 due to the highly transmissible Omicron variant of concern. Although this initial Omicron wave coincided with generally falling trends in all-age ICU admission rates since January 2022[1], some increases in early 2022 were observed in the number of older cases requiring admission to ICU, ventilation or ECMO, most notably among the 80+ age group.

• Despite the context of substantial co-circulation of influenza in most EU/EEA countries, all-cause mortality among age groups 65 and older and older adults (45 to 64) is currently declining[2].

• The EU/EEA has recently experienced an increase in COVID-19 cases among people aged 65 years and above, coinciding with the lifting of public health response measure and the more transmissible BA.2 Omicron sub-lineage becoming dominant. While ICU indicators are currently still low, the impact of this resurgence in the coming weeks will depend in part on the susceptibility of those who are infected to severe disease.

• Analysis of European COVID-19 surveillance data indicates that the highest rates of severe outcomes has been, and continues to be, among unvaccinated people. Within all age groups, occurrence of severe disease is extremely rare among those who have completed the primary vaccination course and/or received an additional booster dose.

• Although great progress has been achieved in uptake of COVID-19 vaccinations in the EU/EEA, there are significant variations in uptake across and within countries and population groups for the primary vaccination series and boosters. In the EU/EEA (as of end of March 2022) 83.3% of the adult (+18 years) population have received a full primary course of vaccination, 63.5% received a booster vaccination[3]. We also observe that vaccine uptake is stagnating. Therefore, continued efforts are needed to increase uptake in primary vaccination series and booster doses.

Vaccine effectiveness and impact in averted morbidity and mortality
• The rapid development and administration of COVID-19 vaccines has provided protection from severe disease and death globally. In 33 countries across the WHO European Region, an estimated 470,000 lives had been saved among those aged 60 years and over [4], as of November 2021[5].

• The number of cases of severe COVID-19 has been significantly decreased by the administration of a booster dose of COVID-19 vaccines after the primary vaccination.[6],[7]

• The effectiveness of current vaccines in preventing infections with the Omicron variant is lower than it was for previous variants,[8],[9] however COVID-19 vaccines continue to be highly effective in protecting all age groups against severe disease, hospitalisation and death.
Waning vaccine effectiveness of protection from severe disease
• Vaccine effectiveness (VE) against severe outcomes is high following the administration of a first booster dose, with estimates of around 80 to 90% protection against severe disease and hospitalisations up to 2 to 3 months after administration of a booster dose, with slight decreases after approximately 4 months.
o In elderly people (aged 70 years and older) in Finland before and after the emergence of the Omicron variant of concern, VE increased to 96% (95% CI, 95 to 97) 14 to 60 days after the third dose.[10] VE of other homologous and heterologous 3-dose series was similar. Protection against severe COVID-19 requiring ICU treatment was even better. Since 1 January 2022, the VE of Comirnaty was 91% (95% CI, 79 to 96) and 76% (95% CI, 56 to 86) 14 to 90 days and 91 to 180 days after the second dose, respectively, and 95% (95% CI, 94 to 97) 14 to 60 days after the third dose.

o In the Czech Republic, the VE of a Comirnaty booster against Omicron hospitalisation was 86% (95% CI, 84 to 89) 14 to 74 days after administration of the booster and reduced to 79% (95% CI, 74 to 82) after more than 75 days.[11] The VE against the need for oxygen therapy following a booster dose was 90% (95% CI, 87 to 92) 14 to 74 days after administration and reduced to 85% (95% CI, 80 to 88) after more than 75 days. The VE against the need for intensive care following a booster was 83% (95% CI, 75 to 89) 14 to 74 days after administration and 60% (95% CI, 37 to 74) after more than 75 days.

o A test-negative, case-control study from Qatar investigated vaccine effectiveness and the effectiveness of natural and hybrid immunity after the administration of a booster dose. The VE against hospitalisation and death was over 90% for both Comirnaty and Spikevax, around 7 weeks after the third dose. The authors concluded that hybrid immunity resulting from prior infection and recent booster vaccination confers the strongest protection against either Omicron subvariant (BA.1 and BA.2) and that vaccination enhances protection of those with a prior infection.[12]

o Among adults in the United States during the Omicron period, VE against hospitalisations was 91% during the first 2 months after a first booster, which decreased to 78% when more than 4 months passed since the first booster. [4]

o A case control mRNA vaccination study[13] performed in the United States focused exclusively on the most severe outcomes of COVID-19, including invasive mechanical ventilation (IMV) and death in adults aged 18 years and above. An overall high VE against IMV or in-hospital death of 90% was estimated. Sub-analysis indicated that while VE hardly decreases with age, it does reduce to a large extent depending on health status (from 92% in immunocompetent people to 74% in immunocompromised people), demonstrating that high levels of durable VE can be obtained by mRNA vaccination in healthy subjects.

o A nationwide cohort analysis from Denmark estimated the vaccine effectiveness against COVID-19-associated hospitalisation. The effectiveness after a booster dose of Cominarty was estimated to 88.8% (95% CI: 87.3 to 34 90.1%), declining to 79.0% (76.5 to 81.3%) in the fourth month, and 66.2 (61.1-70.7) at 4+ months after the booster dose. For Spikevax, the initial effectiveness was 90.2% (87.3 to 92.5%), declining to 83.6% (77.7 to 88.0%) in the fourth month, and 77.3 (63.1-86.1) at 4+ months.[14]

o Another study[15] showed that with the generally milder disease seen with Omicron, contamination of data on hospitalisations with incidental cases reduces VE estimates. With more precise VE estimates, high levels of booster VE against hospitalisation with the Omicron variant have been observed (up to 96%), in particular among older adults who are at greatest risk and against more severe outcomes. Nevertheless, there is evidence of limited waning of protection from 3-4 months after administration of a booster dose.

• Due to the recent exposure of large numbers of the population to the Omicron variant, hybrid immunity, gained from documented previous infection and receipt of a full-vaccination course, is likely to play an increasingly important role in protection at population level.[16],[17],[18] When combined with three vaccine doses, hybrid immunity provides additional population protection in the current context.

Current recommendations on booster doses in EU/EEA countries
• Many EU/EEA countries are currently recommending booster doses at a defined interval following primary vaccination, in light of evidence of waning protection over time.

• For immunocompromised individuals, all 30 EU/EEA countries recommend an additional primary dose as an extension of the primary vaccination course. Twenty countries also recommend a booster dose for immunocompromised individuals following the extended primary three-dose vaccination series (i.e. four doses).

• For the general population, all 30 countries also recommend first booster doses to different age groups due to waning protection. Half of the EU/EEA countries (15/30) recommend booster doses for all adults aged 18 years and over. Fifteen countries recommend boosters for adolescents (either to those over 12 years or those over 16 years).

• As of 5th April 2022, nine countries recommend a second booster dose (fourth dose) for different vulnerable population groups such as residents in long-term care facilities and the elderly, with different age cut-offs (Cyprus, Finland, France, Germany, Greece, Hungary, Ireland, The Netherlands and Sweden). The recommendations for a fourth dose for vulnerable people and certain at-risk groups aim to restore serological responses and overall vaccine efficacy.
The basis for the recommendations is the recorded waning over time of protection afforded by the third dose against infection and symptomatic disease, as well as local epidemiological considerations.[19],[20],[21]

Current recommendations on additional booster doses in other parts of the world
• The Australian Technical Advisory Group on Immunization made recommendations on 25 March 2022 on a fourth COVID-19 vaccine dose to increase vaccine protection before their winter season for some groups, including adults aged 65 and older, residents in long-term care facilities and the severely immunocompromised. On 29 March 2022, the United States Food and Drug Administration (FDA) authorised the use of a second booster dose of either the Pfizer-BioNTech COVID-19 vaccine (Comirnaty in the EU) or the Moderna COVID-19 vaccine (Spikevax in the EU) for individuals 50 years of age and older at least 4 months after receipt of a first booster dose. Following this authorisation, the US Centers for Disease Control and Prevention (CDC) updated their recommendations to allow certain immunocompromised individuals and people over the age of 50 who received an initial booster at least 4 months earlier to be eligible for another mRNA booster.

Effectiveness and safety of a second booster vaccination with mRNA vaccines
• The vaccine effectiveness of a second booster dose has been studied mainly in subpopulations considered to be at higher risk for severe COVID-19. Data are still limited, and all data pertain to the Omicron variant. Effectiveness in preventing infection is observed for a few weeks after the administration of the fourth dose but decreases quickly over time. Early data from Israel indicate that the risk of severe infection and/or death due to COVID-19 is decreased for up to 10 weeks after the administration of a fourth dose as compared to those receiving only the third dose, albeit in populations already experiencing very low levels of severe outcomes and thus providing minimal absolute reduction in severe outcomes. The maximum duration of this protection is not yet known due to short follow-up times in the studies available.

o In an open-label, nonrandomized clinical study[22] conducted during the Omicron period in Israel, the immunogenicity, safety and efficacy of a fourth dose of either Comirnaty or Spikevax was evaluated in healthcare workers when administered at least 4 months after the third dose of Comirnaty. All participants were actively screened for SARS-CoV-2 infection on a weekly basis. The data from this small interventional study showed that administration of a fourth dose does not reveal new serious adverse events and that it restores humoral responses to the highest level seen post-third dose. Only subjects expected to be at higher risk of infection were enrolled in the study (whose IgG antibody levels are below the 40-percentile). Breakthrough infections, nearly all asymptomatic, were very common and VE against SARS-COV-2 infection was not established (point estimates 10-30%, and non-statistically significant). There are no data to show that a fourth vaccination may be of benefit in healthy younger adults.

o During the Omicron period, real-world evidence collected from electronic medical records in Israel and summarized in a pre-print study showed that subjects aged 60 to 100 years, including patients with comorbidities, were significantly less likely to die from COVID-19 if they received a second booster compared to those immunized with only 3 doses at least four months earlier. The absolute risk reduction conferred by the fourth dose was 0.07% in circumstances of high circulation of Omicron variant.[23] Similarly, a preprint for a retrospective test-negative case-control study in Israel showed that subjects 60 years of age or older who received a second booster was 73% effective in preventing severe breakthrough COVID-19 (defined as COVID-19-related hospitalisation or death) during at least 9 weeks of follow-up compared with those who received only the first booster, although severe disease was a rare event (<1%) in both groups and relative effectiveness appeared to wane somewhat over time in the fourth dose group relative to the third dose group.[24] Both studies adjusted their results for differences between the groups with regards to age, gender, socioeconomic status, underlying comorbidities and calendar week of testing.

o Another study among 1.2 million Israelis aged 60 and older estimated vaccine effectiveness of the fourth dose of Comirnaty against SARS-CoV-2 infection and severe illness due to COVID-19.[25] The results showed a 2-times lower rate of confirmed infection and a 3.5-times lower rate of severe COVID-19 in adults in this age group in the fourth week after receiving a fourth dose compared to adults who received a third dose more than four months before. Protection against confirmed infection waned in the later weeks, whereas protection against severe illness did not wane during the short follow period of 6 weeks after receipt of the fourth dose.

• The waning of protection from a second booster dose has not yet been sufficiently studied due to the limited follow-up period. Existing studies are observational and, thus, unavoidably present limitations, including residual confounding factors. Several of the studies are still awaiting peer review. Although studies make adjustments for calendar time, age, and other potential confounders, it cannot be guaranteed that there are no remaining differences between the groups that can influence the VE estimate.

• Despite the relatively small size of the safety database, no major safety issues have emerged following administration of the second booster dose, a finding which is consistent across studies. The EMA will continue monitoring the safety of the second booster closely.

Implementation considerations
• As data on adapted vaccines will be available in the near future and possibly lead to the authorisations of adapted vaccines later on in the year, vaccination campaigns should take into account the impact of repeated booster doses on vaccine acceptance and uptake in the general population. The offer of a fourth dose should be promoted on the basis of an understanding of: (a) public concerns and expectations regarding the vaccines and (b) people’s perceptions and concerns about the disease itself. Behavioural research can offer important insights into vaccination ‘fatigue’ and the low risk perception of the disease among many people today, and thereby providing direction to vaccination campaigns.
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[1] ECDC. https://www.ecdc.europa.eu/en/covid-19/country-overviews
[2] EuroMOMO. https://www.euromomo.eu/bulletins/2022-12/
[3] ECDC Vaccine Tracker
[4] Estimated number of deaths directly averted in people 60 years and older as a result of COVID-19 vaccination in the WHO European Region, December 2020 to November 2021| Eurosurveillance
[5] Estimated number of deaths directly averted in people 60 years and older as a result of COVID-19 vaccination in the WHO European Region, December 2020 to November 2021| Eurosurveillance
[6] Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel | NEJM
[7] BNT162b2 Vaccine Booster and Mortality Due to Covid-19 | NEJM
[8] Effectiveness of mRNA-1273 against SARS-CoV-2 Omicron and Delta variants| Nature Medicine
[9] Vaccine effectiveness against SARS-CoV-2 infection with the Omicron or Delta variants following a two-dose or booster BNT162b2 or mRNA-1273 vaccination series: A Danish cohort study| medrxiv
[10] High vaccine effectiveness against severe COVID-19 in the elderly in Finland before and after emergence of Omicron—medrxiv.org
[11] Protection by vaccines and previous infection against the Omicron variant of SARS-CoV-2—medrxiv.org
[12] Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar
[13] Effectiveness of mRNA Vaccination in Preventing COVID-19–Associated Invasive Mechanical Ventilation and Death — United States, March 2021–January 2022 (cdc.gov)
[14] Vaccine effectiveness against infection and COVID-19-associated hospitalisation with the Omicron (B.1.1.529) variant after vaccination with the BNT162b2 or mRNA-1273 vaccine: A nationwide Danish cohort study
[15] Effectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation: test negative case-control study (khub.net)
[16] Protection against SARS-CoV-2 after Covid-19 Vaccination and Previous Infection | NEJM
[17] Risk of SARS-CoV-2 reinfection and COVID-19 hospitalisation in individuals with natural and hybrid immunity: a retrospective, total population cohort study in Sweden - The Lancet Infectious Diseases
[18] Effectiveness of CoronaVac, ChAdOx1 nCoV-19, BNT162b2, and Ad26.COV2.S among individuals with previous SARS-CoV-2 infection in Brazil: a test-negative, case-control study - The Lancet Infectious Diseases
[19] Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study - ScienceDirect
[20] Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 2022 (cdc.gov)
[21] COVID-19 vaccine surveillance report - week 9 (publishing.service.gov.uk)
[22] Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron | NEJM
[23]Second Booster Vaccine and Covid-19 Mortality in Adults 60 to 100 Years Old | Research Square
[24] Relative Effectiveness of Four Doses Compared to Three Doses of the BNT162b2 Vaccine In Israel | medRxiv
[25] Protection by a Fourth Dose of BNT162b2 against Omicron in Israel | NEJM

ECDC and EMA issue advice on fourth doses of mRNA COVID-19 vaccines | European Medicines Agency [European Medicines Agency, 6 Apr 2022]

The European Centre for Disease Prevention and Control (ECDC) and EMA’s COVID-19 task force (ETF) have concluded that it is too early to consider using a fourth dose of mRNA COVID-19 vaccines (Pfizer’s Comirnaty and Moderna’s Spikevax) in the general population.

However, both agencies agreed that a fourth dose (or second booster) can be given to adults 80 years of age and above after reviewing data on the higher risk of severe COVID-19 in this age group and the protection provided by a fourth dose.

ECDC and EMA also noted that there is currently no clear evidence in the EU that vaccine protection against severe disease is waning substantially in adults with normal immune systems aged 60 to 79 years and thus no clear evidence to support the immediate use of a fourth dose.

Authorities will continue to monitor data to determine if there is an increasing risk of severe illness among those who are vaccinated.

If the current epidemiological situation changes and new signals emerge, it may become necessary to consider a fourth dose in this age group. In the meantime, national authorities will also consider local data in deciding whether to use a fourth dose in those people at higher risk.

For adults below 60 years of age with normal immune systems, there is currently no conclusive evidence that vaccine protection against severe disease is waning or that there is an added value of a fourth dose.

As re-vaccination campaigns could start in the autumn, authorities will consider the best timing for additional doses, possibly taking advantage of updated vaccines.

So far, no safety concerns have emerged from the studies on additional boosters.

Vaccination against COVID-19 remains the most effective way to prevent severe illness during the current pandemic, including severe illness caused by the Omicron variant.

ECDC and EMA urge EU citizens to complete their schedules for both initial and booster vaccinations in line with national recommendations. As of the end of March 2022, 83% of adults had received full initial vaccinations and only 64% had received a booster dose.

What the evidence says about second booster doses
Evidence on the effects of a fourth dose comes largely from Israel, where data indicate that a second booster given at least 4 months after first booster restores antibody levels without raising any new safety concerns. Data also suggest that a second booster provides additional protection against severe disease, although the duration of the benefits is not yet known and the evidence is still limited.

Details of the evidence assessed by both agencies is available in the joint ECDC-EMA statement on second boosters.

Other factors to be considered in vaccination campaigns
National authorities in the EU make final decisions on the roll-out of vaccines, including booster doses, taking into account factors such as the spread of infection, the effects of COVID-19 in different populations and the emergence of new variants.

ECDC and EMA will continue to review available evidence on the effectiveness of COVID-19 vaccines and update their recommendations accordingly. EMA will also consider all emerging data on the safety and effectiveness of booster doses with a view to updating the product information for COVID-19 vaccines where applicable.

Scientists divided on need for 4th Covid shot after FDA quietly approved another round of boosters [CNBC, 6 Apr 2022]

by Spencer Kimball

Leading U.S. scientists and physicians worry that the FDA and CDC are moving too fast in approving a fourth round of Covid shots, with little public debate that gives the vaccine makers too big a role in setting the pace with which the doses are distributed across the nation.

The top U.S. public health agencies last week endorsed a fourth Covid shot for older adults without holding public meetings, drawing criticism from leading vaccine experts who believe federal health officials haven’t provided enough transparency about the reasons for the decision.

The authorization of a fourth dose for adults age 50 and older comes as the scientific community is divided over whether the data is sufficient to support another round of boosters, and whether authorizing additional shots is a sustainable public health policy, especially since protection against infection simply wears off over time. There is a debate over whether the goal of the vaccines is to prevent severe illness, which they’ve largely achieved, or infection as well — a more challenging proposition.

The Food and Drug Administration authorized a second booster shot for people age 50 and older last week, and the Centers for Disease Control and Prevention quickly backed their distribution hours later based on data from Israel, which rolled out fourth doses months ago.
Dr. Peter Marks, who heads the FDA office responsible for vaccine safety and efficacy, said shortly after the decision that another round of boosters will likely be needed in the fall.
Rapid approval

The rapid regulatory clearance of fourth shots for older adults came just weeks after Pfizer and Moderna asked the FDA to permit them. Several FDA and CDC committee members as well as other leading experts said Pfizer and Moderna are playing too large a role in setting the agenda around U.S. vaccine policy by announcing the need for fourth doses and possibly a variant-specific vaccine before the public health agencies have made any recommendations.

Moderna CEO Stephane Bancel said during a January interview with Goldman Sachs that fourth doses would be needed in the fall as the protective antibodies from the shots wane over time. Pfizer CEO Albert Bourla told CNBC in early March, before the company filed its request with the FDA, that there’s a need for a fourth dose though he said the regulators would ultimately come to their own conclusion.

“I just think it’s sort of booster mania. I think the companies are frankly acting like public health agencies,” said Dr. Paul Offit, a member of the FDA committee and one of the nation’s top vaccine experts. Offit said the CDC, which has the final say on vaccine recommendations, needs to develop a clear national strategy to reduce public confusion about what it means to be fully vaccinated at this stage in the Covid pandemic.

Michael Osterholm, a leading epidemiologist, said repeated boosting is not a sustainable public health strategy because of the challenge posed by waning immunity against infection. “We’re not gonna be able to boost our way out of this,” said Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Call for more transparency
The FDA and CDC vaccine advisory panels weigh safety and efficacy data before making recommendations to top federal health officials on the best path forward. Though the recommendations are nonbinding, the meetings provide an open forum where the public can listen to the nation’s top health experts debate the pros and cons of vaccine policy, and often even participate by phoning in to voice their views.

The FDA’s Vaccines and Related Biological Products Advisory Committee is meeting Wednesday to debate the future of boosters. However, it will not vote on any specific recommendations, according to the FDA. The CDC’s Advisory Committee on Immunization Practices did not meet before CDC Director Dr. Rochelle Walensky signed off on the fourth shots for older adults last week.

“It’s just sort of fait accompli,” Offit said. “I feel that we’re in a time, this sort of Covid exceptionalism, where we don’t do things the way we normally do it, which is that the science precedes the recommendation. Here, it’s the other way around,” he said.

Offit said that the FDA is effectively asking the public to believe that the data supports a fourth dose by providing sufficient protection against serious illness. He said the American public benefits from hearing an open discussion about vaccine decisions, particularly at a time when many people are not taking advantage of the third dose. Offit is an infectious disease expert at Children’s Hospital Philadelphia and a co-inventor of a rotavirus vaccine.

Marks, during a call with reporters last week, said the FDA did not call a committee meeting because the decision was “relatively straightforward.” He said data from Israel suggested a fourth dose can reduce the risk of hospitalization and death in older adults. The CDC, in a statement to CNBC, said the fourth dose was an incremental change that did not need to go before its committee.

Dr. William Schaffner, a nonvoting member of ACIP, disagreed that the CDC recommendation was an incremental change. Schaffner said clearing fourth doses for older adults is a big decision that would have benefited from a meeting of outside advisors to provide the public with transparency.

“I think to have this decision made in-house behind closed doors without having the transparency of a full debate that a regularly called ACIP meeting would have provided – I think that’s unfortunate,” said Schaffner, an infectious disease expert at Vanderbilt University Medical Center.

Dr. James Hildreth, who is attending the FDA committee’s Wednesday meeting as a temporary member, noted that the drug regulator wasn’t required to call a public meeting before authorizing the shots, and the agency has seasoned experts who can determine if there is evidence to support a new authorization. However, Hildreth said moving forward without a recommendation from outside experts fuels the perception that industry is playing too big a role in the nation’s vaccine strategy.

“When the FDA makes a decision like that without calling together an outside group of experts, it just adds to the optics of the pharmaceutical companies having an impact on decisions that are being made,” said Hildreth, president of Meharry Medical College in Nashville, Tennessee. Meharry is a clinical trial site for Novavax’s vaccine as well as Moderna’s shots for younger children.

‘Diminishing returns’
While some health experts believe the central purposes of the vaccines is to prevent severe illness, others think it is important to also stop infections from the virus. The protection provided by the Pfizer and Moderna vaccines against infection has declined substantially over time, particularly in the context of omicron, which has numerous mutations that give it an enhanced capability to cause breakthrough infections and mild illness. However, the vaccines are still providing substantial protection against severe illness.

“If you’ve gotten a mild illness after you’ve been vaccinated, you’ve won — that’s it. You’ve been prevented from having serious illness, which is the stated goal of this vaccine,” said Offit, who believes three doses were necessary for the elderly and four for the people with weak immune systems, but is skeptical of the need for additional shots right now.

But if the goal is also to prevent infection, that means, at least for now, booster shots are the only available tool to increase antibodies until a longer-lasting vaccine is available. The problem is that the vaccines eventually run into diminishing returns, according John Moore, a professor of microbiology and immunology at Weill Cornell Medical College. Moore said a three-dose regimen is fairly standard with vaccines to help boost the immune system to its peak response. A fourth shot, however, begins to hit a ceiling — at least in terms of protecting younger people against infection.

The Israeli Health Ministry and scientists at Sheba Medical Center found that a fourth dose does restore antibodies that waned off after a third dose among health-care workers ages 18 and older, but it provided little protection against infection. Pfizer cited that study, which has not undergone peer-review, among others in its statement on the FDA authorization, focusing on the increased antibodies without highlighting the issues with breakthrough infections.

Different age, different needs
Dr. Peter Hotez, a vaccine expert at the Baylor College of Medicine in Houston, strongly supports a fourth dose for older adults, pointing to a CDC study from February that found the third shot’s effectiveness against hospitalization dropped from 91% to 78% after four months.

Pfizer, in its public statements on the fourth dose, cited a separate Israeli study that found a fourth dose reduced mortality by 78% in people ages 60 and over. The study from Ben Gurion University and Clalit Health Services, which has not undergone peer-review, analyzed the medical records of more than 500,000 people.

’We continue to collect and assess all available data and remain in open dialogue with regulators and health authorities to help inform a Covid-19 vaccine strategy as the virus evolves,” Pfizer said in a statement to CNBC.

While the Ben Gurion study may point in the direction of a benefit for older adults at the moment, the evidence for boosting younger adults again is scant as the U.S. considers lowering the eligibility for fourth doses sometime later in the year.

Dr. Gili Regev-Yochay and her team of scientists at Sheba said a fourth dose “may only have marginal benefits” for younger people, according to a letter published in the New England Journal of Medicine. While Pfizer originally filed for adults age 65 and older, Moderna asked the FDA authorize a fourth dose for ages 18 and older. Moore called Moderna’s filing “aggressive,” arguing that it didn’t distinguish between the needs of the elderly, who may benefit from an additional dose, compared with younger adults where the data is less convincing.

Moderna CEO Bancel told CNBC last month that the company wanted to give the FDA flexibility to decide which age group would benefit most from a fourth shot right now.
Moderna, in its public statements on its application for a fourth dose, pointed to data from Israel but didn’t cite specific studies.

Though Hotez supports a fourth dose for older adults, he said the FDA and the CDC have not done an effective job at communicating whether the goal of the vaccines is to prevent severe illness, infection or both, and the vaccines makers have filled that void with statements on data from their clinical trials and lab studies. Hotez and a team of scientists in Texas developed a Covid vaccine, Corbevax, based on traditional protein-based technology that has received authorization in India.

Hotez also expressed frustration that the U.S. relies heavily on data from abroad, particularly Israel and the U.K. Offit also questioned why the U.S. is relying on data from countries that are smaller than the U.S. and have different demographic backgrounds.

Long-term strategy needed
Hildreth said the U.S. should put off additional booster doses as long as the public health situation allows so the nation can more clearly define how it measures protection against the virus and develop a long-term strategy to achieve that end. He said if the public is asked to get boosted every several months, many people will simply stop listening.

“We don’t know a specific measure we can do to say whether or not a person is truly protected, and whether or that’s the same with everybody,” said Hildreth. For example, there’s no clear measure of whether a certain level of antibodies is sufficient to protect people, he said.

Beyond vaccination with the current vaccines, Pfizer and Moderna are developing shots that target omicron as well as other variants. Dr. Arnold Monto, who is chairing the FDA’s committee meeting on booster strategy Wednesday, said public health authorities need to develop a consensus about what goes into the vaccines moving forward. Monto said collaboration between the vaccine makers and the government is crucial, but industry has started playing a larger public role in decisions about about what kind of vaccines should be developed to target specific Covid variants.

“Industry has a double-headed goal. They are trying to do public good like we all are. They also have stockholders, and we need to be sure that the public health good is kept mind,” Monto said.

New Coronavirus News from 11 Apr 2022

The latest Covid-19 subvariant: XE [The Daily Briefing, 11 Apr 2022]

A new coronavirus subvariant, called XE, contains a combination of the omicron variant BA.1 and the BA.2 subvariant, known as "stealth" omicron. And while it has infected around 600 people in the United Kingdom, experts say "there's still a lot we don't know about XE."

What we got right (and wrong) in our Covid-19 predictions

What is XE?

The XE subvariant contains a combination of the omicron variant BA.1, which first surfaced in late 2021, and the BA.2 subvariant, known as "stealth" omicron—currently the dominant variant around the world.

XE is a "recombinant" virus—a type of variant that can occur when an individual has a coinfection of two or more variants at the same time, mixing the variants' genetic features within a patient's body. Notably, XE is the fifth recombinant virus that has stemmed from omicron, USA Today reports.

Although data on XE's severity and ability to evade immunity is not yet clear, early estimates suggest it could be more contagious than earlier strains, CNBC reports.

According to data from the UK Health Security Agency (UKHSA), XE has a growth rate that is 9.8% higher than BA.2—a figure the World Health Organization estimates to be 10%.

"This particular recombinant, XE, has shown a variable growth rate and we cannot yet confirm whether it has a true growth advantage. So far there is not enough evidence to draw conclusions about transmissibility, severity or vaccine effectiveness," said UKHSA chief medical advisor Susan Hopkins.

Where has XE been detected?

In the U.K., the earliest confirmed case of XE has a specimen date of Jan. 19, which means it could have been circulating in the population for several months, CNBC reports. In total, UKHSA has confirmed 637 cases of XE. It has since also been identified in Thailand.

The U.K. is currently facing a Covid-19 surge, largely driven by the BA.2 subvariant, and the XE variant currently accounts for less than 1% of total cases that have gone through genomic sequencing in the UK.

Are experts worried about XE?

Jeremy Luban, an infectious disease specialist at the University of Massachusetts Medical School, said he is monitoring XE but is not concerned yet.

"XE has a powerful combination of all these variants of coronavirus. Should it spread rapidly through the U.S. at some point, we would be concerned," Luban said.

Separately, William Schaffner, an infectious disease specialist at the Vanderbilt University School of Medicine, said there is no reason to panic.

"There's still a lot we don't know about XE," Schaffner said. "XE could surprise us, so we have to wait to see how severe it will be."

Notably, Schaffner said he is more concerned about BA.2, which currently accounts for 72% of Covid-19 cases in the United States and remains the dominant variant around the world.

On Tuesday, CDC Director Rochelle Walensky noted that even though BA.2 has sparked several outbreaks around the world, it has not caused a significant increase in cases in the United States. In fact, Walensky said cases dropped 4% from the previous week, and hospitalizations and deaths both declined by over 16%.

According to Schaffner, variants will continue to pose a risk to the world's "return to normalcy" because of their unpredictability. "This is our new reality, variants popping up everywhere because fortunately, we are detecting them," he said. "The more we can find, the more we can study and contain."

New Coronavirus News from 12 Apr 2022

Peter Hotez: What omicron XE COVID variant means for summer 2022 [Houston Chronicle, 12 Apr 2022]

by Andrew Dansby

Dr. Peter Hotez is celebrating a few milestones: Corbevax, a COVID-19 vaccine developed by a team he and Dr. Maria Elena Bottazzi led, has reached 20 million children in India. Indonesia and Botswana also approved the protein-based vaccine last week.

Hotez —dean of the National School of Tropical Medicine at Baylor College of Medicine and co-director of the Center for Vaccine Development at Texas Children’s Hospital — made the announcements in his typically understated way, via Twitter.

The Houston-based Hotez continues to track the pandemic near and far, charting infection rates in the U.S. as well as Texas, while reminding people that global vaccination is crucial to stopping the variants that have marched through the States.

Hotez took time to field questions about Corbevax, the BA.2 variant and what two years of COVID-19 may mean for summer 2022.

Q: I feel like we always start with Texas. But for a change of pace, could you talk about how the Corbevax rollout is going in India?

A: Corbevax is going to have multifacted uses. It can be used both as a pediatric vaccine, an adult vaccine and also as a booster vaccine for both populations. That’s the way I break it down. But we’ve worked with Biological E in India and got emergency authorization last year.
The first population it is going into as of March was kids 12 to 14. And so far the Ministry of Health estimates about 20 million kids in India age 12 to 14 across the country have gotten their first dose of Corbevax. So that’s exciting.

There are other things happening. As those numbers start to climb, there are clinical studies confirming safety and efficacy in five to 11 year olds that are rolling out. So we hope that happens in the next few weeks as well. So we should see kids in India from 5 to 14 vaccinated.

You might ask why it’s not going to adults there. The reason is because so many adults in India have gotten the AstraZeneca or the Chinese inactivated virus vaccines. Those have been used for adults, and our vaccine could be used as a booster to improve protection because the effectiveness of those vaccines against the variants has not been very strong. … All of this has relevance globally. It should feed into other global approvals. In the meantime the government in Botswana approved Corbevax as a vialed vaccine or in bulk. They’re looking at 100 million doses. You might ask why a country with 2 million people, which is what Botswana is, needs that many doses. That’s because they want to be purveyors and providers of the COVID vaccine for that part of the continent. Not only Botswana, but also Namibia, Zambia, Zimbabwe, the list goes on.

Q: You’ve long maintained Asia and Africa need the vaccines to halt variants that keep reaching here. How do you feel about future variants with these rollouts?

A: I think when I look at the new variants that are a threat to the United States, I break them into two components. Component 1 are brand new variants totally unrelated to things we’ve seen before. We have a track record of this with alpha and then delta and then omicron. I still worry about more of those emerging in lower- and middle-class countries. We may see something like that this summer in Texas and Southern states. We saw big epidemics in the summer in Texas in 2020 and 2021 into the fall. So I worry about that.

The other side of this is the fact that BA.2 arose out of the same town where omicron arose.
So I’m concerned we may see down the road some spinoffs of BA.2. And BA.2 has been partially successful infecting some individuals with omicron previously. So we may see new fronts. But the first is brand new variants unrelated to previous ones. The others are those that might step out of the initial omicron wave: from omicron to BA.2 to BA.X or some type of combination. My colleague Trevor Bedford at the University of Washington does modeling on this front. And he wrote about sub-subvariants of BA.2 that we may have to think about as well.

Q: That said, mask mandates are going away, events are taking place again. If you look at those maps of the U.S., the states in crimson are gone. How do you feel about that going forward with BA.2?

A: So a few things about BA.2: BA.2 is not necessarily behaving in the same way the other variants of concern did. We saw the alpha variant and the delta variant go up as a percentage of total virus isolates in the U.K. followed immediately by a wave. Then the wave subsequently hit the U.S. BA.2 in western European countries, it’s not as straightforward. In some countries BA.2 is becoming a dominant variant and cases are up. In others it’s not dominant and cases are not going up. Or cases are going up, but it’s not BA.2. It’s a messier picture. But there’s no question BA.2 — if you look at wastewater or virus isolates — there’s no question it’s becoming the dominant variant in the U.S. How much that could translate into another big wave is the big unknown. It does look now like it’s translating into case numbers going up in New York state and New York City; Washington, D.C. Nancy Pelosi just got infected. Whether that’s a consequence of BA.2 going up or becoming a full-blown wave, we don’t know. Maybe it’s more a bump that goes up and then down. That’s unknown. How it could reach different part of the country is unknown. For example the alpha variant, we saw it hang up there in Michigan for a while. And it had less impact in other places. We could see something along those lines.

Q: School is winding down and travel and camps are about to start back up. What do you think about summer? Two years ago we heard the suggestion that summer would kill this thing. And here we are.

A: The thinking was that upper respiratory coronaviruses pre-pandemic showed winter spikes, but they weren’t big players in the summer. But summer 2020 was a rude wake-up call for Texans, who were devastated. The vaccine wasn’t out yet. So it was devastating for Hispanic populations, essential workers and some low-income communities that got hit hard. Essential workers didn’t have the option of staying home and doing things through Zoom. But in multi-generational households, a 22-year-old construction worker could come home and infect parents and grandparents. The following summer was a different scenario altogether. In 2021, Texas had another huge wave, but it was different after the vaccine became widely available.
Those going into hospitals and ICUs were largely those defying the vaccine. The demographics were quite different, with a lot of groups in Texas being hesitant and defying the vaccine because of political allegiance, as self-defeating as that was.

Q: I’ve had several parents and parents-to-be asking about the vaccine for kids 5 and under.
Do you think that’ll be here soon? And what do you expect it do do?

A: Well, I think even for a pediatric vaccine, what we saw with both Pfizer and Moderna was that the dose of the vaccine was greatly reduced, the dose of the mRNA component. As a consequence, the immune responses were not as strong. We may have underdosed a bit too much. Whether it meets the immunological criteria to say the immune response is adequate to release them for emergency use is the big question. So they may wait for a third dose before they go and greenlight it. I think that’s what we’re waiting for.

Q: This is anecdotal based on friends, family and colleagues, but I feel like I’m hearing about more breakthrough cases among those who have received three doses. Am I reading too much into this?

A: Well a few things: We thought once you got that third immunization — based on what the data from alpha and delta looked like — once you got that booster, that third dose, we thought you were done. You had a big bump in virus-neutralizing antibodies, and it looked like the protection was holding up well. It wasn’t one-and-done or two-and-done. But we thought three, you’re done. We’ve had this conversation.

But clearly with omicron and BA.2, something else is happening. That protection is neither as durable nor as strong as we’d thought. Against the third dose vs. omicron, four months after you got it, protection against hospitalization went down to 78 percent. And protection against ER visits went to 66 percent. Still pretty good, but not as good as it was. Even against infection, you were still 3.6 times less likely to get omicron if you were fully vaccinated and boosted compared to an unvaccinated individual. So there were more breakthrough infections, but not as many and certainly with less severity. But those declines were sufficient to make people concerned about maybe needing a second booster, a fourth immunization. I’m a big proponent of that. I think it will help a lot — data from Israel suggests that.

The big unknown now with omicron and BA.2 is the durability of protection not holding up as well. That means what? They started those conversations at the FDA advisory committee meetings yesterday, but I was a bit disappointed that they didn’t come up with much in the way of conclusions. I think the situation is this: the mRNA vaccine … every vaccine has its strengths and weaknesses, including ours, and including the mRNA vaccines. It may be with mRNA vaccines, until we fix the technology, that the durability won’t be as strong as we’d like.
Therefore, what’s the plan? Let’s say for now, we try to convince a lot of American people to get a second booster. I got my second booster. Four or five months from now, will we need a fifth booster? Or do we try to think outside the box and bring in another vaccine technology that might give you longer lasting and more enduring protection?

Q: What might that look like?

A: I think it could be a protein-based vaccine like ours. The problem is that we’re not seeing that higher-ordered thinking coming from the federal government right now. In public statements, we’re not seeing any movement toward trying to convene experts to say, “Hey, maybe giving mRNA vaccines in perpetuity may not be the best strategy. Maybe it’s the only choice, but we’re not seeing that discussion yet. That’s the next big thing I’m looking for: convening experts, which isn’t something that’s happening in the FDA advisory meetings to inform us what else we need to do assuming this pandemic continues.

Q: I feel like each time we talk, we’d have better information if we waited two weeks. But I guess that’s the nature of this.

A: And the answer is we do, actually. But it’s still not complete. The omicron variant and BA.2 are disappointing. We thought we had this thing figured out with a third dose lasting, giving five- or six-year protection; we thought that would buy us more time to think about this. Now now we’re already thinking about what happens this fall. Do you ask the American people to get a fifth dose? Do you ask immunocompromised people to get a fifth dose? Will they accept that? If you look at the numbers, fewer than half of Americans eligible for the first booster got it. For a second booster, there’ll probably be further drop off. You’re going start seeing people getting more fed up.

Q: Have you observed that sort of fatigue elsewhere in the world?

A: Israel seems to have buy-in. But again, one problem is that a country doesn’t speak with one voice. There’s one part of our country that is very much in tune with what the CDC says. And there’s a part of the country that completely tuned out and wants no part of it — people who won’t get a booster or who aren’t even vaccinated at all. This is part of the problem I see coming from the White House. And that’s a challenge for the new coordinator, Ashish Jha, will have. Because trying to speak to the whole country with one voice is really problematic. It has been in the past. It comes out as babytalk. If you try to reach all parts of the country with one message, you wind up serving nobody.

Q: What are your thoughts on the “XE” variant?

A: By XE, I think you mean the sort of hybrid. I think we’re going to see recombination hybrid variants coming along. That’s what I mean when I talk about the next generation BA.2. I call it BA.X. Which … then the question is going to be do we finally get around to making an omicron booster? I don’t know the answer to that. There’s some evidence that there are these recombinant variants like XE, so should we make an omicron-specific booster?

On the other hand, there was an important paper in the medical journal “Cell” that suggested if you’re getting vaccinated and boosted with a vaccine connected to the original lineage, you may not respond robustly to a booster made up of the variant. There’s a phenomenon in our field called “original antigenic sin,” which means whatever you started with, that’s basically driven the immune system in one direction. And it’s hard to bring it back to a new variant through boosting. There’s both data for and against that. And that could be a bigger problem. In the past I’ve said — even in the recent past — there’s no point in making an omicron-specific booster. But if we continue to see bumps if not waves of omicron — things like BA.2 and XE — there may be logic to that.

New omicron XE Covid variant first detected in the UK spreads to Japan as cases rise [CNBC, 12 Apr 2022]

by Karen Gilchrist

Japan has reported its first case of omicron XE — a new Covid-19 strain first detected in the U.K. — just as British cases of the subvariant rise.

The XE variant was found in a woman in her 30s who arrived at Narita International Airport from the U.S. on March 26. The woman, whose nationality was not immediately disclosed, was asymptomatic, Japan’s health ministry said Monday.

It comes as cases of the new strain have almost doubled in Britain, according to the latest statistics from the U.K. Health Security Agency.

As of April 5, 1,125 cases of XE had been identified in the U.K., up from 637 on March 25. The earliest confirmed case has a specimen date of Jan. 19 of this year, suggesting it could have been in circulation in the population for several months.

XE has since been detected in Thailand, India and Israel. It is suspected that the latter Israeli cases may have developed independently. The U.S. has not yet reported any XE cases.

What is omicron XE?
XE is what’s known as a “recombinant,” a type of variant that can occur when an individual becomes infected with two or more variants at the same time, resulting in a mixing of their genetic material within a patient’s body.

In the case of XE, it contains a mix of the previously highly infectious omicron BA.1 strain, which emerged in late 2021, and the newer “stealth” BA.2 variant, currently the U.K.’s dominant variant.

Such recombinants are not uncommon, having occurred several times during the course of the coronavirus pandemic. However, health experts say it is too soon to draw conclusions on the new subvariant’s severity or ability to evade vaccines.

“We continue to monitor cases of the recombinant XE variant in the U.K., which currently represents a very small proportion of cases,” Meera Chand, director of clinical and emerging infections at UKHSA, said in a statement.

On Sunday, the U.K. reported 41,469 new Covid cases, with a seven-day average of 59,578 cases. As such, XE likely accounts for only a small percentage of total Covid cases currently.

How worried should we be?
Early estimates suggest XE may be more transmissible than earlier strains, having so far demonstrated a slightly higher growth rate than its predecessor.

UKHSA data shows XE has a growth rate of 9.8% above that of BA.2, while the World Health Organization has so far put that figure at 10%.

However, experts say they expect it to wane in severity even as it spreads more easily. XE has so far not been declared a variant of concern.

“XE seems to be moving in the same direction as BA.2, having an increased transmissibility to BA.1 but being less severe,” Jennifer Horney, professor of epidemiology at the University of Delaware, told CNBC.

“It is the devil we know, so to speak. [It is] essentially a reshuffling of the same deck of cards,” added Mark Cameron, associate professor in the School of Medicine at Case Western Reserve University.

XE contains spike and structural proteins from the same virus family, i.e. omicron, meaning that it should, theoretically at least, behave as omicron has done before. Existing vaccines and immunity should, therefore, provide some level of protection against infection.

“Recombinants that contain the spike and structural proteins from a single virus (like XE or XF) are fairly likely to act similarly to [their] parental virus,” Tom Peacock, virologist at Imperial College London’s Department of Infectious Disease, wrote in a thread of tweets in mid-March.
XF refers to another recombinant previously detected in the U.K. in February.

However, other recombinants containing spike and structural proteins from different virus families continue to emerge. That includes the XD subvariant, recently discovered in Germany, the Netherlands and Denmark, which contains delta structural proteins and omicron spike proteins and which Peacock described as “a little more concerning.”

As such, all new emergences need to be closely monitored, especially in their early phases, to ensure they don’t evolve into something more serious.

“The virus is still capable of evolving, recombining and developing a new branch of its family tree,” Cameron said.

“The key takeaway is that for each of these variants and subvariants, risk of hospitalization and death appears to be, on average, lower where vaccination rates are higher, indicating that vaccination, including a third dose, should be effective in reducing risk for severe disease,” added Stephanie Silvera, professor of public health at Montclair State University.

Shanghai tweaks lockdown rules amid COVID-19 surge [Al Jazeera English, 12 Apr 2022]

City will be divided into three tiers depending on recent cases amid rising anger over food shortages and lack of necessities.

Shanghai has eased a punishing citywide lockdown that it imposed to break a surge in cases that is the biggest test of China’s two-year strategy to stamp out the disease wherever it appears.

Authorities in Shanghai introduced the three-tier disease control system on Monday, allowing residents in areas where no cases have been reported for 14 days to leave their homes so long as they follow health protocols and remain in their sub-district.

Those living in areas where no cases have been confirmed for seven days are allowed to collect food deliveries or take a walk at a designated time and location.

City health official Wu Qianyu emphasised the need for continued controls at a press briefing.

“After a long period of lockdown, it is understandable that people want to go out and get some air, and they need to go shopping for food and medicine and go for medical treatment,” she said. “But if lots of people gather in a disorderly way, it will cause hidden dangers to our epidemic prevention work.”

Of the city’s 17,600 communities, however, some 7,624 remain in the strictest lockdown designation and people there are required to stay at home.

Gu Honghui, deputy secretary-general of the Shanghai municipal government, said the zoning would be updated regularly based on the situation in each community.

“Our principle, as always, is to strive to minimise the impact of the epidemic on residents’ daily lives,” Gu told the daily briefing on the city’s epidemic control situation.

The Shanghai outbreak is the most severe since the initial surge in cases in Wuhan that triggered the global pandemic, and is proving to be a considerable test of China’s ‘zero COVID’ strategy, which relies on mass testing, quarantine and draconian lockdowns to stamp out the virus.

Anger over restrictions
But the Shanghai lockdown, which was initially supposed to be just a few days long, has fuelled anger among residents who have complained about food shortages and a lack of basic necessities.

On Tuesday, the United States said it had ordered all non-essential consulate staff to leave the city, citing the COVID response. The US earlier advised its consulate staff to leave and also urged Americans to reconsider travel to China due to “arbitrary enforcement” of local laws and COVID-19 restrictions, particularly in Hong Kong, Jilin province and Shanghai in an announcement that drew anger from Beijing.

China was “strongly dissatisfied with and firmly opposed to the US side’s groundless accusation against China’s epidemic response,” Foreign Ministry Spokesperson Zhao Lijian said on Sunday.

Guangzhou, a sprawling metropolis of 18 million people on China’s southern coast, is also battling an outbreak of the disease and is conducting a mass testing campaign.

Residents have been advised not to travel unless absolutely necessary and the city has been closed to arrivals from outside.

Guangzhou’s health commission said it had found 27 new confirmed local cases and 11 asymptomatic cases as of Monday evening. A total of 61 infections have been reported in the current outbreak since Friday.

China is still mainly closed to international travel, even as most of the world has sought ways to live with the virus.

Mainland China reported a total of 24,659 confirmed cases on April 11, most of them people without symptoms, the national health authority said on Tuesday. More than 23,000 cases were in Shanghai.

Shanghai COVID lockdown lifted for some, but millions remain trapped as China sticks to strict "zero-COVID" policy [CBS News, 12 Apr 2022]

Tokyo — The U.S. State Department has ordered all non-emergency consular staff to leave China's largest city, Shanghai, as the global business hub enters its third week of lockdown in response to a surge in COVID-19 cases. The U.S. Embassy in Beijing said it was ordering the departure because of the outbreak in Shanghai and as American diplomats had raised "concerns about the safety and welfare of U.S. citizens" in the city.

"It is best for our employees and their families to be reduced in number and our operations to be scaled down as we deal with the changing circumstances on the ground," a statement from the embassy said, according to The Associated Press.

Shanghai officials reported more than 23,000 new coronavirus cases on Tuesday. The vast majority of them are asymptomatic, but despite that, and some limited easing of the restrictions, the government has largely stuck to its strict lockdown and isolation measures — even as it battles public anger, food shortages and a major impact on business.

China's central government has bristled at criticism of its tactics from the U.S. and Europe, insisting over the weekend that its draconian "zero-COVID" policy was "effective and scientific."
Analysts at the global financial services firm Nomura estimated that as many as 45 cities in China were implementing either full or partial lockdowns as of Tuesday, impacting more than a quarter of the country's overall population, according to the Reuters news agency.

As CBS News senior foreign correspondent Elizabeth Palmer reports, Shanghai is under the single biggest COVID lockdown in the world. For more than two weeks, the megacity of more than 25 million people has been eerily quiet.

The only bustle is at food depots, where there's a daily race to deliver groceries to millions of people who haven't been allowed out to shop.

Amid an outcry from residents, city authorities on Tuesday did allow people in some COVID-free neighborhoods to leave their homes, and officials said some pharmacies and grocery stores would reopen, too.

A local news outlet said fewer than 7 million Shanghai residents were being liberated, however, and details on who would be freed and when remained murky.

American Billy Stockton, who lives and works in Shanghai, is among the millions who have been confined to their apartments since late March.

"No one knows where to get stuff," he told Palmer. "No one knows where to get medical help… and it's creating panic, fear and, just, instability."

There have been angry protests — rare anywhere in China — in areas where food ran out. Videos posted to social media show crowds of frustrated residents shouting, "we're starving!"
Last week, a man vented his fury in a video recorded on his phone, and then uploaded online.

"What am I supposed to buy," he shouted. "What do I eat? You're driving us to our deaths!"
Small groups of residents have now been allowed out over the past couple weeks, but only briefly, for COVID testing. Anyone who tests positive has no choice: As one patient showed on TikTok, they had to board a special bus and then check into a government-run mass-isolation center.

The authorities are clearly ready to quarantine an onslaught of new cases, even as they release old ones who are now testing negative.

But for the recently released, it's a false sense of freedom. The roughly 6,000 people who were let out of isolation centers on Monday headed straight back into lockdown at home.

Looking out of Billy Stockton's window, however, there was no sign of that. He was busy taking stock of his dwindling food supply.

"I have sausages and then they supplied a bag of rice yesterday, so simple stuff like that," he said of his meal plan.

"It's like a movie," he told Palmer, saying he felt like he was trapped in a nightmare. "I just can't believe I'm in this. It's beyond surreal. You kind of have to pull yourself out of it to get through it."

Like millions of other Shanghai residents, Stockton has no choice but to just get through it.

That could take another couple of weeks, however, and the question is whether there will be lasting fallout among Shanghai's massive population, who have rarely, if ever, felt so mistreated and abused by their government.

New Coronavirus News from 10 Apr 2022

China labels U.S. concerns over COVID regulations 'groundless accusations' [Reuters.com, 10 Apr 2022]

SHANGHAI, April 10 (Reuters) - China's foreign ministry expressed "strong dissatisfaction" with the United States late on Saturday after it raised concerns over China's coronavirus control measures.

The U.S. State Department said on Friday that non-emergency staff at its Shanghai consulate and families of U.S. employees could leave due to a surge in COVID cases and coronavirus restrictions in the city.

"We express strong dissatisfaction and firm opposition to the groundless accusations against China's pandemic prevention policy from the U.S. in its statement, and have lodged solemn representations," foreign ministry spokesperson Zhao Lijian said in a statement.

Shanghai is fighting China's worst COVID-19 outbreak since the virus first emerged in Wuhan in late 2019, with almost 25,000 new local cases reported on Sunday for the previous day.

While those case numbers are small by global standards, Shanghai's curbs to battle the outbreak have squeezed supplies of food and other essential goods for the city of 26 million, with residents also raising concerns about access to medical care.

The most controversial of Shanghai's practices had been separating COVID-positive children from their parents. Authorities have since made some concessions.

"Ambassador (Nicholas) Burns and other Department and Mission officials have raised our concerns regarding the outbreak and the PRC's control measures directly with PRC officials," a U.S. Embassy spokesperson said in a statement on Saturday, referring to the People's Republic of China.

"We have informed them about the voluntary departure decision," the statement said.

Friday's advisory said that U.S. citizens should reconsider travel to China "due to arbitrary enforcement of local laws and COVID-19 restrictions."

The advisory also warned Americans from travelling to Hong Kong, Jilin province or Shanghai, citing a risk of parents and children being separated.

China's foreign ministry said on Saturday that China's pandemic prevention and control is "scientific and effective", adding that the government had assisted foreign diplomatic personnel as much as possible.

Diplomats from more than 30 countries recently wrote to China's foreign ministry to express concern with the separations.

China reports 1351 new confirmed COVID cases on April 9 vs 1350 a day earlier [Reuters.com, 10 Apr 2022]

BEIJING, April 10 (Reuters) - China reported 1,351 new confirmed coronavirus cases on April 9, the national health authority said, compared with 1,350 the day before.

Of the new cases, 1,318 were locally transmitted, the National Health Commission said, compared with 1,334 on April 8.

The number of new asymptomatic cases, which China counts separately, stood at 25,111, compared with 23,815 a day earlier.

There were no new deaths, the commission said in data released on Sunday, leaving the death toll in China unchanged at 4,638.

As of April 9, mainland China had confirmed 164,393 cases.

Why China Sticks With Costly Lockdowns and 'Zero COVID' [Newsweek, 10 Apr 2022]

BY JOHN FENG

A s the occupants of a high-rise apartment block in western Shanghai sang from their windows in the third week of China's harshest COVID lockdown since the beginning of the pandemic, a small drone carrying a loudspeaker sought to quell their benign protest with a dystopian message: "Dear residents ... Please strictly comply with the municipal government's epidemic prevention regulations. Control your soul's desire for freedom and refrain from opening your windows to sing. This behavior carries a risk of transmission."

Like many countries in the West, the United States has done away with most rules surrounding public health. Some argue the measures were never restrictive enough to be begin with.
America's nearly 1 million COVID-19 deaths are now the go-to gibe in Beijing whenever Washington mentions the condition of human rights in China, where the death toll remains at a little more than 4,600.

With nearly 90 percent of China's population fully vaccinated, many observers outside the country—and some within—are wondering why policymakers still refuse to abandon their "zero-COVID" approach, despite fears that the strategy is becoming untenable.

In Shanghai, the eastern port city of 25 million, there was a sign of Beijing's lingering anxieties when Sun Chunlan, vice premier, arrived over the weekend. In spring 2020, Sun was dispatched to Wuhan, and wasn't recalled from central China until after the city had ended its lockdown. Her appearance in China's financial capital came on the back of a month of record daily cases, which continue to rise due to the Omicron BA.2 variant, in what has quickly become the country's most alarming outbreak in its most populous city.

The megacity has been at a standstill since late March. Citywide testing is underway, and exhibition centers are being converted into centralized quarantine facilities in moves that evoked scenes from Wuhan, which was abruptly shut down in order to stem a disease whose lethality wasn't fully known. But in Shanghai, where residents found themselves confined to their homes, workplaces and, in one case, even a public toilet as part of the sweeping clampdown on the virus, the recent surge has so far produced one severe case and no deaths, according to official data, despite a buildup of more than 100,000 mostly asymptomatic cases in the new epicenter.

Upon arrival, however, Sun—the only woman on the Chinese Communist Party's powerful 25-member Politburo—dashed any idea the leadership might change tack from what it calls "dynamic zero COVID"; on the contrary, Beijing is doubling down.

Sun ordered local health officials to "act quickly and forcefully" to stop the spread of the virus, stressing "unswerving adherence" to China's zero-tolerance approach by mandating lockdowns, centralized quarantine and mass testing. Tens of thousands of beds will be made available to isolate patients, and the military has been called in to assist.

Sun has put the city on a war footing not seen since workers erected emergency field hospitals in Wuhan, operations she was tasked with overseeing.

A Costly Trade-Off
Shanghai's chaotic response to the crisis suggests local leaders were woefully unprepared to impose such stringent measures.

Last month residential neighborhoods where positive cases were found were sealed off, and officials took a stepped approach to containment to protect the economy. The municipal government drew up plans for a two-stage snap lockdown that would split the city in two by the Huangpu River. But on March 27, an indefinite COVID shutdown was extended citywide, catching many residents and officials off guard.

This job is not a job—it's costing me my life. Sun Chunlan is here. I hope she has good policies.

Shanghai neighborhood official
Decision-makers were well aware of the economic impact of a full lockdown of Shanghai, a financial hub home to vehicle and electronics plants as well as semiconductor suppliers, and the world's busiest shipping port. The day before the announcement, Wu Fan, a member of the city's pandemic response team, told reporters: "If Shanghai, this city of ours, came to a complete halt, there would be many international cargo ships floating in the East China Sea," he said. "This would impact the entire national economy and the global economy." This week, French investment bank Natixis slashed China's 5.5 percent GDP growth targeted by 1.8 percentage points for the first quarter.

Yanzhong Huang, a senior fellow for global health at the Council on Foreign Relations, describes Shanghai's COVID policy U-turn as a "strange twist."

Each locality is held accountable for disease control, failing which Beijing can use its "central playbook," he says. "For the supporters of that policy, it's not just politically justifiable, it also makes sense from a public health perspective, especially when they foresee a worst-case scenario."

According to some projections, abandoning the zero-COVID strategy could overwhelm China's healthcare system and lead to more than 1 million deaths. "But the question here is to what extent the worst-case scenario is likely. I think many of the policymakers, those who believe the zero-COVID approach, overestimate the likelihood," he says.

Huang notes factors including China's high vaccination rate and epidemiological data from Shanghai and Hong Kong that show Chinese-made inactivated vaccines can significantly reduce the risk of severe cases and death.

"In my opinion, there is a better, more cost-effective approach that may not be able to avoid the surge of cases when opened up, but it can minimize the damage by minimizing the number of fatalities and severe cases; by, more importantly, avoiding disruption to society and the economy," he says.

It would call for boosting the country's public health surge capacity, educating the public about the risks of the virus, effective triage procedures, and aggressively vaccinating the elderly.
"This would represent a more viable alternative to the zero-COVID strategy," says Huang, who is also a professor at Seton Hall University.

As the occupants of a high-rise apartment block in western Shanghai sang from their windows in the third week of China's harshest COVID lockdown since the beginning of the pandemic, a small drone carrying a loudspeaker sought to quell their benign protest with a dystopian message: "Dear residents ... Please strictly comply with the municipal government's epidemic prevention regulations. Control your soul's desire for freedom and refrain from opening your windows to sing. This behavior carries a risk of transmission."

Like many countries in the West, the United States has done away with most rules surrounding public health. Some argue the measures were never restrictive enough to be begin with. America's nearly 1 million COVID-19 deaths are now the go-to gibe in Beijing whenever Washington mentions the condition of human rights in China, where the death toll remains at a little more than 4,600.

With nearly 90 percent of China's population fully vaccinated, many observers outside the country—and some within—are wondering why policymakers still refuse to abandon their "zero-COVID" approach, despite fears that the strategy is becoming untenable.

In Shanghai, the eastern port city of 25 million, there was a sign of Beijing's lingering anxieties when Sun Chunlan, vice premier, arrived over the weekend. In spring 2020, Sun was dispatched to Wuhan, and wasn't recalled from central China until after the city had ended its lockdown.
Her appearance in China's financial capital came on the back of a month of record daily cases, which continue to rise due to the Omicron BA.2 variant, in what has quickly become the country's most alarming outbreak in its most populous city.

The megacity has been at a standstill since late March. Citywide testing is underway, and exhibition centers are being converted into centralized quarantine facilities in moves that evoked scenes from Wuhan, which was abruptly shut down in order to stem a disease whose lethality wasn't fully known. But in Shanghai, where residents found themselves confined to their homes, workplaces and, in one case, even a public toilet as part of the sweeping clampdown on the virus, the recent surge has so far produced one severe case and no deaths, according to official data, despite a buildup of more than 100,000 mostly asymptomatic cases in the new epicenter.

Upon arrival, however, Sun—the only woman on the Chinese Communist Party's powerful 25-member Politburo—dashed any idea the leadership might change tack from what it calls "dynamic zero COVID"; on the contrary, Beijing is doubling down.

Sun ordered local health officials to "act quickly and forcefully" to stop the spread of the virus, stressing "unswerving adherence" to China's zero-tolerance approach by mandating lockdowns, centralized quarantine and mass testing. Tens of thousands of beds will be made available to isolate patients, and the military has been called in to assist.

Sun has put the city on a war footing not seen since workers erected emergency field hospitals in Wuhan, operations she was tasked with overseeing.

A Costly Trade-Off
Shanghai's chaotic response to the crisis suggests local leaders were woefully unprepared to impose such stringent measures.

Last month residential neighborhoods where positive cases were found were sealed off, and officials took a stepped approach to containment to protect the economy. The municipal government drew up plans for a two-stage snap lockdown that would split the city in two by the Huangpu River. But on March 27, an indefinite COVID shutdown was extended citywide, catching many residents and officials off guard.

“This job is not a job—it's costing me my life. Sun Chunlan is here. I hope she has good policies.”

Shanghai neighborhood official
Decision-makers were well aware of the economic impact of a full lockdown of Shanghai, a financial hub home to vehicle and electronics plants as well as semiconductor suppliers, and the world's busiest shipping port. The day before the announcement, Wu Fan, a member of the city's pandemic response team, told reporters: "If Shanghai, this city of ours, came to a complete halt, there would be many international cargo ships floating in the East China Sea," he said. "This would impact the entire national economy and the global economy." This week, French investment bank Natixis slashed China's 5.5 percent GDP growth targeted by 1.8 percentage points for the first quarter.

Yanzhong Huang, a senior fellow for global health at the Council on Foreign Relations, describes Shanghai's COVID policy U-turn as a "strange twist."

Each locality is held accountable for disease control, failing which Beijing can use its "central playbook," he says. "For the supporters of that policy, it's not just politically justifiable, it also makes sense from a public health perspective, especially when they foresee a worst-case scenario."

According to some projections, abandoning the zero-COVID strategy could overwhelm China's healthcare system and lead to more than 1 million deaths. "But the question here is to what extent the worst-case scenario is likely. I think many of the policymakers, those who believe the zero-COVID approach, overestimate the likelihood," he says.

Huang notes factors including China's high vaccination rate and epidemiological data from Shanghai and Hong Kong that show Chinese-made inactivated vaccines can significantly reduce the risk of severe cases and death.

"In my opinion, there is a better, more cost-effective approach that may not be able to avoid the surge of cases when opened up, but it can minimize the damage by minimizing the number of fatalities and severe cases; by, more importantly, avoiding disruption to society and the economy," he says.

It would call for boosting the country's public health surge capacity, educating the public about the risks of the virus, effective triage procedures, and aggressively vaccinating the elderly. "This would represent a more viable alternative to the zero-COVID strategy," says Huang, who is also a professor at Seton Hall University.

Hints of Unrest
The social impact of the governments's decision was felt in days.

China's social media platforms are awash with videos of residents protesting about a lack of daily necessities including food, water and other forms of welfare support. Images emerged of standoffs between citizens and police, and instances of micro-level cruelty against people and animals, performed in the name of upholding the law. One grim example saw a worker in a hazmat suit beat a corgi dog to death with a shovel, after its owner had been taken into quarantine, according to one social media account. The inspector was apparently concerned that the pet could inadvertently spread the virus.

This debate on zero COVID or coexistence with the virus is no longer just a debate between which method works better. It's characterized now as a competition between two political systems, even two civilizations.

Yanzhong Huang, Council on Foreign Relations
In another case of helplessness, a mother in Shanghai complained of inadequate social distancing enforcement in a phone call with her neighborhood health official, only to be met with surprising frankness from the woman on the other end of the line. In a recording of the nine-minute conversation, the sobbing official said her supervisors weren't taking her calls, and that she'd rather be isolating at home too, instead of dealing with irate residents who were likely carrying COVID. "This job is not a job—it's costing me my life," she cries. "Sun Chunlan is here. I hope she has good policies."

The inhabitants of Shanghai have become the living embodiment of the Chinese proverb "the crying child gets the milk"; however, it's hard to say whether social grievances will lead to a meaningful change in the government's approach.

Politics Lead the Way
It may be that fewer and fewer experts see the practical merits of continuing a similar policy in any country at this point in the pandemic.

But inside Zhongnanhai, zero COVID emerges from a specific assessment about continued socio-political stability in 2022, a year in which China's President Xi Jinping is expected to tout his political achievements as reasons to be re-elected at the CCP's 20th National Congress this autumn. Accordingly, party ideology is part of the approach to public health.

In an April 6 letter from the CCP's Shanghai Committee, members were told to bravely "draw swords and fight" against actions that interfere with or undermine the anti-epidemic battle.

"Those who step forward in critical moments and risk everything in times of crisis are real Communists," it read.

The Chinese public doesn't directly vote its national leaders into power, but the legitimacy of the leadership matters. There's no question that China's successful containment of COVID compared to the West has won Xi overwhelming support at home.

April 8 marks the second anniversary of Wuhan's lifting of its 76-day lockdown in 2020. Two months after the city reopened, at the delayed "Two Sessions" political convention in Beijing, the CCP all but declared victory over the virus, while the West had yet to experience the worst of the disease. In public addresses since, Xi has put his country forward as a leader in global health. China reported its first COVID deaths in over a year last month.

A new COVID wave is probably coming, and America just doesn’t seem to care [Fortune, 10 Apr 2022]

BY ERIN PRATER

It was a viral moment that elicited both nervous laughs and tears of joy from a pandemic-weary nation: Colorado Gov. Jared Polis awaiting his state's first COVID vaccine shipment in December 2020, staring at a delivery door like a child stares at a fireplace on Christmas Eve.

“Any minute now we’re going to hear a doorbell,” Polis says with childlike glee, his words muffled by a surgical mask.

“And then we’re going to ….” He dramatically pauses before saying, “of course, let the vaccine in.”

Before he finishes his sentence, a bell shrieks.

“Ope, there we go!” Polis exclaims, making a rapid rotation to hit a button and open the warehouse door.

“This is the Pfizer vaccine, arriving here in Colorado, to end the pandemic!” he exclaims as the door opens slowly, awkwardly revealing a delivery man who perhaps wasn’t aware he’d been chosen to save mankind—or at least Coloradans.

Polis’ giddy anticipation mirrored the mental state of so many Americans in those weeks before Christmas 2020. The potential side effects were unnerving, maybe, but the vaccine was coming.

To end the pandemic and nine months of isolation and tragedy.

That was the hope. But it wasn’t reality.

“I think some of it is just human nature, that you want to believe there will be a quick technological fix,” Fractal Therapeutics CEO Arijit Chakravarty told Fortune. His position is summed up by the headline of his searing new article published to Lancet-affiliated preprint journal medRxiv: “Endemicity is not a victory: the unmitigated downside risks of widespread SARS-COV2 transmission.”

Scenarios under which the U.S. sees surges of a variant more deadly than any seen before are plausible, Chakravarty and his colleagues contend.

Hundreds of thousands of deaths could ensue annually, they say. COVID could become the No. 1 cause of death in the U.S., beating out the most common maladies like heart disease and cancer.

“It’s not a specific prediction about the future,” Chakravarty hedged. “We’re not saying the world will end on Tuesday, April 7, 2024. But the goal is to make people say, ‘Gee, some scenarios out there are really quite ugly.’”

A ‘one-way ceasefire’
Chakravarty isn’t alone in worrying about what happens next. He has good company in Dr. Anthony Fauci, the infectious disease expert who has become the face of America’s COVID response. He said this week that a surge of COVID is likely this fall, and an increase in cases over even the next few weeks would not be surprising.

Fauci’s remarks contrast with a sudden vanishing of the Omicron wave that gripped the country in December and January (and ruined many people’s holiday plans). Cases fell so far so fast that big cities like New York relaxed mandates that had been in place for nearly two years. In New York’s case, famously unvaccinated celebrities like basketball star Kyrie Irving are free to play indoors again, and masks are off at most restaurants and retail outlets, bringing it in line with the rest of the country.

March is seeing cases creep back up again as bosses consider a widespread return to the office.

When it comes to the blissful oblivion of many to the pandemic’s continued existence, “motivated reasoning” is to blame, says psychologist Paul Thagard, a philosopher and cognitive scientist who authored the paper “The cognitive science of COVID-19: Acceptance, denial, and belief change.”

Another term for motivated reasoning: “a complicated version of wishful thinking.”

“People look at what makes them happy instead of evidence,” Thagard says. “This virus has been very unpredictable. People want to believe it’s going to get better and better. It’s not based on solid knowledge of the biology of the virus.”

If another severe wave of COVID were to hit the U.S., Thagard predicts the country would see a similarly large wave of denial, “one more application of motivated reasoning.”

“Right now things don’t look that bad in North America, generally, because hospitals aren’t that full. That could change fairly quickly.”

Vaccines aren't enough Current vaccines have failed to end the pandemic.

That’s a key argument Chakravarty and his coauthors make in their new paper.

It’s a reality, they say, that so many are failing to recognize as they buy into the scenario that the pandemic is becoming milder and will continue to, and that the pandemic is shrinking to endemicity and will continue to shrink in scale.

“Public-health authorities in many countries have advocated for a strategy of using the vaccines to limit morbidity and mortality while permitting unchecked SARS-CoV-2 spread (‘learning to live with the disease’),” Chakravarty’s team writes.

But that strategy seems to rely on future waves of COVID being less deadly, either due to weaker but more transmissible strains of the virus taking hold, or due to population immunity that is inevitably temporary, the authors write. And it ignores the fact infection fatality rates of future COVID variants may wax and wane.

“Omicron was mild. Maybe if there’s a BA.3, it will be mild too,” Chakravarty says. “But just because it was named Omicron 3 doesn’t mean it couldn’t be its own beast.”

Writing the paper wasn’t easy, Chakravarty says.

“We, as a team, went back and forth—this took months to write,” he says. “Emotionally, it’s a difficult conclusion to come to. It doesn’t help you sleep well at night.”

Regarding COVID, “You have to mitigate the risk of the worst thing without having a big debate about whether or not it’s going to happen today. People aren’t really having that conversation.”

He and his colleagues realize an approach like China’s zero COVID policy isn’t sustainable. The team recommends an approach of “subtle changes” that “don’t require endless amounts of personal sacrifice,” and that “slow down evolution and work on limiting the spread.”

Among their proposals: upgrading air quality and ventilation in buildings, since most transmission occurs indoors; widespread surveillance of virus transmission; and focusing on the development of preventative medicines and next-generation vaccines that can reduce the spread.

But with Congress bickering over a $10 billion COVID aid bill and the U.S. running out of funds for things like vaccines and research, the U.S. is quickly losing its ability to “see what’s happening and react nimbly.”

“We’re more and more flying blind,” he says.

A World Health Organization official recently aid we may be entering a "period of ceasefire" with the virus, but Chakravarty says "it takes two parties to agree to a ceasefire. Another word for a one-way ceasefire? Surrender.”

'We get comfortable with what happens' Chakravarty says America is now rolling the dice with its COVID strategy.

Dr. Georges Benjamin, executive director of the American Public Health Association, says it’s the no-plan plan.

In short: The American approach to COVID seems to be “ignore it and hope it goes away, and hope the interventions we have right now are functional enough to make it tolerable,” he says.

“And the answer is, not yet. We have good tools. We’re better than we were two years ago, but this virus is pretty tricky. It’s fooled us every time we thought we understood something.

“In many ways, we were unprepared and playing catch-up.”

COVID isn’t the only public health crisis about which Americans have become complacent, Benjamin says.

“We get tired of an issue,” he says. “We park it. We get comfortable with what happens.
Thousands of people die from gun violence every year. That’s something that, when it happens, particularly mass shootings, everyone says, ‘It’s terrible. We must do something.’

“But the political will to do something about it quickly fades.”

He worries the most about politicians getting COVID fatigue and potentially failing to pass another COVID aid bill to fund, among other things, surveillance of the virus and research on new variants.

“Resource allocators have a tendency to, when something happens, throw a lot of money at it—usually not quite enough, never for long enough,” he says. “Then they withdraw funding, and their expectation of performance far exceeds the money put into it.

“We’re seeing that happen right now.”

A cautionary tale This isn’t the first time Americans have turned a blind eye toward disease, says John M. Barry, author of “The Great Influenza: The story of the deadliest pandemic in history.”

The 1918 flu pandemic “killed young people and children, and the elderly largely escaped it—despite that, people grew tired of taking precautions.”

The flu, an H1N1 virus thought to have originated in birds, was first identified in the U.S. in the spring of 1918. It spread worldwide in waves, infecting about a third of the world’s population and killing at least 50 million, with about 675,000 deaths in the U.S. alone, according to the U.S. Centers for Disease Control and Prevention. Many were previously healthy young adults and young children.

When it comes to America’s collective memory, the flu pandemic was left out, a seeming historical amnesia.

“That’s the single question I was asked most when my book came out in 2004: ‘How come I never heard of this?’” he says.

He’s not entirely sure, though it might have something to do with people at the time being more accustomed to death by infectious disease, World War I, and historians writing about “what people did to people,” but not about what nature did to people.

Thagard offers a cautionary tale: a fourth wave of the 1918 flu pandemic that came in 1920 at a time when the public was weary.

“They pretty much entirely ignored it—and the fourth wave, in some cities, was the deadliest yet,” Barry says.

“People just didn’t want to deal with it, just as we don’t want to deal with it.”

New Coronavirus News from 8 Apr 2022

Japan considers 4th doses of COVID-19 vaccines [NHK WORLD, 8 Apr 2022]

Fourth dose under discussion
Japan's health ministry is considering whether to authorize a second booster, or fourth dose, of a coronavirus vaccine as the efficacy of a third dose reportedly wanes over time. Though no decision has been taken yet, the ministry says local authorities should complete the groundwork for a rollout, arranging vaccination coupons and venues, by around the end of May.

Slow uptake for booster shots
Though more than 80 percent of Japan's elderly people have received a booster shot, the rate for the population as a whole was just 44 percent as of April 7. Some experts say the delay is one of the reasons for the failure to bring the infection rate under control.

Research in Israel
Research has shown that a third shot is more effective against the Delta variant than the currently dominant Omicron variant. The efficacy also declines as time passes. As a result, some nations have already begun administering fourth shots.

On March 16, the New England Journal of Medicine published the results of a study in Israel that found the first booster was key to maximizing immunity, and that a second booster was effective primarily in restoring antibody levels that had diminished since a third dose.

The researchers looked at 154 medical workers who had received a Pfizer shot for their fourth dose, and 120 medical workers who received the Moderna shot. They found that both vaccines were only one tenth as effective against Omicron as against the original virus. They say a fourth dose for young, healthy people may have only marginal benefits.

Pfizer claims that when people aged 60 or older receive a fourth shot more than four months after a third shot, it cuts the number of infections in half, and reduces the number who develop serious symptoms by 75 percent.

Around the world
On March 29, the US Food and Drug Administration authorized fourth doses of the Pfizer-BioNTech and Moderna vaccines for people aged 50 or above who got their third shot at least four months ago, and for people under 50 who are immunocompromised.

The United Kingdom, France, Germany, South Korea and Israel are already offering second booster shots–in most cases limited to the elderly, residents of care homes, medical workers and the immunocompromised.

No need to rush
Immunologist Miyasaka Masayuki, guest professor at the Osaka University Immunology Frontier Research Center, says that even though the ability to prevent serious illness can decline, a resurgence of efficacy can be expected after a fourth shot, based on the data from Israel among other sources.

He says the level of neutralizing antibodies rises to a certain level after a fourth shot and that is enough from the perspective of immunology.

"Immune system could be weakened, especially in older people, and people with underlying health conditions such as diabetes and cardiac problems, so they are highly likely to be the target of the fourth dose," Miyasaka says. "We don't need to rush to provide a fourth dose, but it is important to prepare for it as variant strains with higher pathogenicity or infectivity could emerge."

As for the vaccine interval, he doesn't recommend receiving a fourth too soon after a third dose, and that leaving a long-enough interval can produce high-quality antibodies.

He says that a third dose activates the B cells, a kind of immune cell, that create antibodies, so before a fourth dose, waiting for a sufficient period to develop B cells is highly likely to produce antibodies that can respond to various variant strains.

Take the first booster, prepare for the next
Tokyo Medical University Hospital Professor Hamada Atsuo, an expert on infectious diseases, says it is good to provide a fourth shot to older people who have a higher risk of serious illness and medical workers about six months after their third. But, he also emphasizes that the current priority is to increase the coverage of third shots to more than 50 percent in April or May to seek an exit strategy to get society and the economy back on track. Our immediate challenge is to continue taking basic anti-infection measures and, at the same time, to bring daily life back to normal.

This information is accurate as of April 8, 2022.

Fauci expects uptick in COVID-19 cases in coming weeks, another surge in the fall [FOX 9 Minneapolis-St. Paul, 8 Apr 2022]

By Stephanie Weaver

BETHESDA, Maryland - White House medical adviser and infectious disease expert Dr. Anthony Fauci said he expects another increase in COVID-19 cases in the coming weeks in the United States, with a more serious surge that could arrive in the fall.

"I would not be surprised if we see an uptick in cases," Fauci said during an exclusive interview with Bloomberg Television on Wednesday.

Fauci noted that the increase could come "over the next couple of weeks," potentially fueled by the high transmissibility of BA.2 — a subvariant of the omicron variant.

Fauci says we could see COVID-19 surge in fall
Fauci, who is also the director of the U.S. National Institute of Allergy and Infectious Diseases, noted that it is very difficult to accurately predict when the next surge will happen, but said, "it is likely that we will see a surge in the fall" when the weather gets cooler and as immunity from the virus wanes.

Currently, about half of eligible Americans have received booster shots, and there have been nearly 80 million confirmed infections overall.

Some states have shown small rises recently in COVID-19 cases, but overall cases are still at the lowest since last summer and hospitalizations are at a pandemic low.

But most health experts cite that immunity from the COVID-19 vaccine wanes over time, so the best way to avoid another surge is by getting more people vaccinated and boosted against the virus.

COVID-19 booster may be effective against BA.2 variant, study shows
In fact, new evidence released last month showed a booster dose of the coronavirus vaccine may provide protection against BA.2.

Researchers from Beth Israel Deaconess Medical Center examined neutralizing antibodies produced after vaccination or infection.

The study, funded in part by the National Institutes of Health’s National Cancer Institute and published in the New England Journal of Medicine, found that after a booster vaccination, levels of antibodies in the blood that could bind to and neutralize a new omicron variant increased substantially.

"After the booster dose, levels of antibodies that could neutralize BA.2 jumped substantially.
The number that could recognize BA.2—as well as BA.1—after the booster dose was higher than those recognizing the original virus after only the first two shots," the NIH wrote. "

Fauci hopes US won’t see surge in hospitalizations
If an uptick does become a surge, Fauci said he hopes the U.S. won’t see a large increase in hospitalizations due to existing background immunity.

The NIH is currently conducting studies to determine what the best booster in fall should be — an omicron boost or a boost of the original ancestral strain. The U.S. Food and Drug Administration and its committee also met this week to discuss how and when vaccines should be modified.

US death toll from COVID-19 hits 900,000
In February, the U.S. death toll from COVID-19 hit 900,000. President Joe Biden lamented the milestone, saying, "After nearly two years, I know that the emotional, physical, and psychological weight of this pandemic has been incredibly difficult to bear."

He again urged Americans to get vaccinations and booster shots.

"Two hundred and fifty million Americans have stepped up to protect themselves, their families, and their communities by getting at least one shot — and we have saved more than one million American lives as a result," Biden said.

As of Friday, 75.6% of adults in the U.S. were fully vaccinated, or about 195 million Americans, according to the Centers for Disease Control and Prevention. Some 98.4 million people have received a booster dose of the vaccine.

One study from earlier this year used those factors and others to estimate that 73% of Americans were, at the time, immune to omicron. And according to health experts, this could prevent or shorten new illnesses in protected people and reduce the amount of the virus circulating overall, likely tamping down new waves.

Immunity from virus, vaccination may ease wave of COVID-19 cases
"When you combine the immunity that many people have following infection, with the immunity that people who have been vaccinated and hopefully boosted have, there’s a significant amount of background immunity," Fauci continued.

Fauci: US ‘likely’ to see fall COVID-19 surge [The Hill, ８ Apr 2022]

BY NATALIE PRIEB

President Biden’s chief medical adviser Anthony Fauci predicted Wednesday that there will likely be a rise in COVID-19 cases in the coming weeks as well as a potential surge in the fall.

“I think we should expect, David, that over the next couple of weeks, we are going to see an uptick in cases – and hopefully there is enough background immunity so that we don’t wind up with a lot of hospitalizations,” Fauci told Bloomberg TV’s David Westin.

Fauci, who serves as director of the National Institute of Allergy and Infectious Diseases, said that the increase in infections could come as a result of waning immunity and the loosening of COVID-19 restrictions across the U.S.

“Those conditions are also present in the United States,” he said. “So, I would not be surprised if we see an uptick in cases. Whether that uptick becomes a surge where there are a lot more cases is difficult to predict.”

When Fauci was asked whether the U.S. will be faced with a similar COVID-19 surge in the fall as the country has experienced for the past two years, he said the prospect is “likely,” noting that “these are uncharted waters for us with this virus.”

“I would think that we should expect that we are going to see some increase in cases as you get to the colder weather in the fall,” he said. “That’s the reason why the [Food and Drug Administration] and their advisory committee are meeting right now to plan a strategy, and we at the [National Institutes of Health] are doing studies now to determine what the best boost would be.”

Over the past two fall seasons during the pandemic, the U.S. has experienced a surge in cases due to the holiday season when families gather and the colder weather that forces people indoors.

Fauci’s remarks come as the BA.2 variant, which has an increased level of transmissibility compared to the original omicron strain, has become the dominant variant in the U.S.

New York City and Washington, D.C., have seen a rapid rise in coronavirus cases over the past two weeks, according to The New York Times COVID-19 tracker. However, the cases are still relatively low compared to January’s spike.

The coronavirus is also making its way through Congress. House Speaker Nancy Pelosi (D-Calif.) tested positive for the disease earlier this week. Following the news of her infection, Sen.
Susan Collins (R-Maine) announced she had tested positive for COVID-19.

B.C. scientist wins prestigious national award for work on mRNA COVID-19 vaccine [Global News, 8 Apr 2022]

By Simon Little

A British Columbia biochemist whose work played a key role in the development of COVID-19 vaccines has been honoured with one of Canada’s most prestigious scientific awards.

Biochemist Pieter Cullis, former director of UBC’s Life Sciences Institute, was named a winner of the 2022 Canada Gairdner International Award on Tuesday.

He was honoured alongside Katalin Karikó, senior vice-president of RNA Protein Replacement Therapies at BioNTech SE and Drew Weissman, director of the Penn Institute for RNA Innovation, for their work developing the vaccine’s mRNA engineering.

“It’s astonishing, really,” Cullis told Global BC Morning on Friday.

“This really reflects the work of hundreds of people. I had the privilege of leading some pretty successful groups, but this is really a group effort and a very collaborative endeavour.”

Technology developed over decades by Cullis and his colleagues was used in the Pfizer-BioNTech messenger RNA (mRNA) vaccine.

Scientists have been working with mRNA, which can direct cells in the human body to produce proteins for decades, but one of the key challenges in its use in medicine was how to deliver it safely into cells.

That’s where Cullis’ work was important. Cullis and UBC colleagues pioneered the development of lipid nanoparticles, tiny droplets of fat that work to create a “bubble” around mRNA and allow it to travel to cells in the body.

“You need a delivery system both to protect it from the external environment and also to carry it across the cell membrane. Without a delivery system, the mRNA would not get into the cell, and therefore not make the protein it codes for,” Cullis explained.

Unlike traditional vaccines, which involve the use of an inert form of a virus, messenger RNA vaccines work by teaching human cells how to create a protein that triggers an immune response.

In the case of COVID-19, they direct he cells to produce proteins that mimics the spike protein that allows the SARS-SoV-2 virus to interact engage with our cells.

Messenger RNA research itself has been ongoing since the 1980s.

Cullis and B.C. researchers have been working on lipid nanoparticle technology for decades, and in 2009 he and colleagues Thomas Madden and Michael Hope launched a private company, Acuitas Therapeutics, which later partnered with Pfizer-BioNTech to develop their mRNA vaccine.

Those decades of work, Cullis said, belies the popular misconception that mRNA COVID-19 vaccines were developed “overnight.”

“This is work that has been going on in my laboratory and others for over 25 years now,” Cullis said.

“It certainly is a different form of vaccine, but it’s not one you can say has been developed overnight. This has been a gradual improvement in technology so that we can actually use nucleic acid polymers as therapeutics.”

Madden, president and CEO of Acuitas, described work to actually produce the vaccine as a sprint that involved sending scores of different formulations to BioNTech for pre-clinical work.

“We were doing that at at time where we still needed to ensure the safety of people at Acuitas who were doing this work — most other businesses were locked down,” he said.

“People were working seven days a week, 24-hours a day ins some cases, in order to be able to quickly turn around all of these different vaccine candidates so that the best ones could move into phase one clinical trials.”

Cullis said he believes the technology used in the vaccine has massive potential, and could one day be used to treat other diseases including cancer.

It’s a potential the Gairdner Foundation also saw, noting the honorees “pivotal discoveries also have the potential to revolutionize the future delivery of effective and safe vaccines, therapeutics and gene therapies.”

“This is work that has been going on in my laboratory and others for over 25 years now,” Cullis said.

“It certainly is a different form of vaccine, but it’s not one you can say has been developed overnight. This has been a gradual improvement in technology so that we can actually use nucleic acid polymers as therapeutics.”

Madden, president and CEO of Acuitas, described work to actually produce the vaccine as a sprint that involved sending scores of different formulations to BioNTech for pre-clinical work.

“We were doing that at at time where we still needed to ensure the safety of people at Acuitas who were doing this work — most other businesses were locked down,” he said.

“People were working seven days a week, 24-hours a day ins some cases, in order to be able to quickly turn around all of these different vaccine candidates so that the best ones could move into phase one clinical trials.”

Cullis said he believes the technology used in the vaccine has massive potential, and could one day be used to treat other diseases including cancer.

It’s a potential the Gairdner Foundation also saw, noting the honorees “pivotal discoveries also have the potential to revolutionize the future delivery of effective and safe vaccines, therapeutics and gene therapies.”

New Coronavirus News from 7 Apr 2022

People urged to stay vigilant as coronavirus infections rebound in Japan — again [The Japan Times, 7 Apr 2022]

Merely two months after the peak of the sixth wave, coronavirus infections are already rebounding in Japan, with experts again urging people to stay vigilant by getting vaccine booster shots, wearing masks and avoiding crowded places.

The seven-day average of new COVID-19 infections stood at 46,594 as of Tuesday, up from 43,250 the week before and increasing for two weeks in a row. New infections had been gradually declining for several weeks after the government in January began implementing quasi-emergency measures, which restricted business hours for restaurants and some activities.

The lifting of those measures nationwide in late March, an uptick in people’s movement around the April start of the new school and business year, and the spread of the highly transmissible BA.2 omicron subvariant are seen as factors behind the rebound. Experts said the situation needs close monitoring given that new cases are increasing in all age groups, but particularly among teens and those in their 20s.

Low vaccination rates among young people were discussed in a meeting Thursday between Prime Minister Fumio Kishida and Shigeru Omi, the nation’s top coronavirus adviser. In an apparent attempt to entice younger people to get their third jabs, the government is reportedly considering offering discounts for music and sports events to people who have received booster shots.

“The level of new infections remains higher than in the peak we experienced last summer, and a potential rebound is a concern,” Takaji Wakita, chair of the health ministry’s COVID-19 advisory board, said after its weekly meeting Wednesday.

On the bright side, as the weather gets warmer, it becomes easier for people and businesses to ventilate indoor spaces, which can help reduce infections, Wakita said. People will also spend less time indoors, helping prevent the spread of the virus, he said.

But Hiroshi Nishiura, a mathematical modeling expert at Kyoto University, presented a grimmer outlook, saying “a seventh wave has already started.” He cited a resurgence in infections in many prefectures in recent days.

The pathogen fueling the current case increase is the BA.2 sublineage, a heavily mutated version of the coronavirus. BA.2 is more transmissible than the original omicron variant, BA.1, which led to record numbers of infections in Japan in February. Now accounting for 70% of new cases, BA.2 is expected to make up 90% of all new cases by the first week of May, according to surveillance data provided by the National Institute of Infectious Diseases.

Between the two variants, there has been no difference reported when it comes to vaccine efficacy or the risk patients will develop severe symptoms, meaning the treatments and prevention measures needed will be the same, said Motoi Suzuki of the NIID.

As the coronavirus continues to mutate, a new set of highly transmissible variants known as “recombinant variants” have been detected overseas. A recombinant variant occurs when an individual becomes infected with two or more variants at the same time, resulting in a mixing of their genetic material within the patient’s body, according to the U.K. Health Security Agency. The U.K. has already reported more than 600 cases of XE — a recombinant of the omicron variant’s BA.1 and BA.2.

In China, which is seeing its biggest outbreak since the coronavirus was first detected in Wuhan, authorities have reported two novel omicron subvariants that don’t match any existing sequences, according to Bloomberg News. It’s unclear how serious the symptoms caused by them are and whether they pose a significant risk.

Nishiura said Japan should also keep an eye on XE and other new variants.

“XE’s transmissibility is certainly higher than that for BA.1 or BA.2,” Nishiura said. “If people’s international mobility increases, XE has a high chance of replacing the current omicron variants. But we still don’t know the severity of symptoms among the infected people, so we need to examine the epidemiological impact of the variant closely.”

The omicron variant, first detected in South Africa last November, quickly overtook delta as the dominant strain worldwide. Many people infected with the omicron variant have developed mild or no symptoms, although the variant is far more infectious than delta. More recently, BA.2 has fueled a resurgence of infections worldwide.

BA.2’s generation time, or the time between the start of infection in a primary case and the start of infection in a secondary case, is slightly shorter than with BA.1, with both at around two days. Omicron’s generation time as a whole is also shorter than delta’s, which is around five days. The shorter the generation time, the harder it becomes to control an outbreak.

A new coronavirus variant combination, XE, has been detected in the UK. Here's what we know. [USA TODAY, 7 Apr 2022]

by Gabriela Miranda

A new variant of the coronavirus has emerged in the U.K., but it’s too soon to know whether it should be cause for concern.

Called XE, it is a combination of two versions of omicron, named BA.1 and BA.2. It’s common for viruses to recombine, experts said.

Since XE was identified in early January, it has infected about 600 people in the U.K.. It’s not clear whether XE is more contagious than BA.2, and there is no indication it can cause more severe disease.

XE “has shown a variable growth rate and we cannot yet confirm whether it has a true growth advantage.” Susan Hopkins of the U.K. Health Security Agency said in a statement. “So far there is not enough evidence to draw conclusions about transmissibility, severity or vaccine effectiveness.”

Dr. Jeremy Luban, an infectious disease specialist at the University of Massachusetts Medical School, said he’s watching XE but is not worried yet.

“XE has a powerful combination of all these variants of coronavirus. Should it spread rapidly through the U.S. at some point, we would be concerned,” Luban said.

Dr. William Schaffner, an infectious disease specialist at the Vanderbilt University School of Medicine in Nashville, Tennessee, said there’s no reason to panic

“There’s still a lot we don’t know about XE,” he said. “XE could surprise us, so we have to wait to see how severe it will be.”

He said he's more concerned about BA.2, which accounts for 72% of COVID-19 cases in the USA and is the dominant variant worldwide.

BA.2 has led to several outbreaks around the world but is not driving up cases substantially in the USA. Cases dropped 4% compared with a week earlier, and hospitalizations and deaths are both down more than 16%, Dr. Rochelle Walensky, director of the Centers for Disease Control and Prevention, said Tuesday.

What exactly is XE?
The British Health Security Agency confirmed 637 cases of XE, the earliest on Jan. 19.
As a mix of two variants, XE is what’s called a recombinant virus. This mixing of viral DNA is so common that XE is the fifth recombinant virus involving omicron.

The British Health Security Agency identified XD and XF as combinations of delta and omicron BA.1.

In the U.K., 38 cases of XF have been identified, all before mid-February, and there is no evidence that this version of the virus is being transmitted within the country.

Forty-nine cases of XD have been reported in global databases, the majority in France.

Infectious disease experts worry that a variant will develop that’s as contagious as BA.2 and as lethal as delta, but all the omicron-related variants have caused less severe disease.

The vaccines have provided good protection from severe illness and death from the variants, though a third vaccine dose is needed to provide the same level of protection against omicron as against earlier variants.

Because of their unpredictability and dangerous potential, variants will continue to pose a threat to the world’s “return to normalcy,” Schaffner said.

“This is our new reality, variants popping up everywhere because fortunately, we are detecting them,” he said. “The more we can find, the more we can study and contain.”

New Coronavirus Variant XE Identified, Spreading in U.K. [U.S. News & World Report, 7 Apr 2022]

by Cecelia Smith-Schoenwalder

Early estimates suggest XE is 10% more transmissible than ‘stealth omicron,’ which would make it the most transmissible variant yet.

A new coronavirus variant that could be the most transmissible yet has been identified in the United Kingdom.

The variant, known as XE, is a combination of the omicron subvariants BA.1 and BA.2. It was first detected in the U.K. on Jan. 19, according to the World Health Organization, though it has since been reported in India as well. As of late March, roughly 600 cases of it were identified.

According to the U.K. Health Security Agency, there is evidence of community spread of the variant in England. However, it currently is responsible for less than 1% of sequenced infections.

Early estimates suggest XE is 10% more transmissible than BA.2 – sometimes referred to as “stealth omicron” – which would make it the most contagious variant yet. But WHO states in a recent report that “this finding requires further confirmation.” Its level of severity is not yet known.

The development comes as BA.2 has taken over both worldwide and in the U.S. as the dominant variant. While some states in the U.S. have started seeing increases in new coronavirus cases, experts don’t expect BA.2 to lead to another surge.

WHO is tracking XE under the umbrella of omicron, so as of now, it does not have its own Greek letter name. The organization said that “XE belongs to the omicron variant until significant differences in transmission and disease characteristics, including severity, may be reported.”

XE is an example of a so-called “recombinant” event, which involves two virus strains mixing their genetic material in the same cell that then replicates. WHO is also tracking another recombinant nicknamed “deltacron” that has been found in European countries but so far has not yet alarmed experts either.

WHO notes that “recombination is common among coronaviruses and is regarded as an expected mutational event.”

New Coronavirus News from 9 Apr 2022

Dr. Fauci explains why US will see a new COVID surge this fall [Deseret News, ９ Apr 2022]

By Herb Scribner

A new coronavirus outbreak will begin in the fall, according to Dr. Fauci
There will likely be an uptick in COVID-19 cases in the next few weeks, but a true coronavirus surge will happen this fall, according to Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases.

The news: Bloomberg TV’s David Westin asked Fauci about the potential for a new coronavirus outbreak in the United States from the BA.2 variant.

• Fauci said the United States often lags behind the United Kingdom, which has seen a recent surge in cases.
• The BA.2 variant — a subvariant of the omicron variant — and opening up by loosening restrictions will contribute to an uptick in cases, Fauci said, per CNN.

What Fauci said: “I think we should expect, David, that over the next couple of weeks, we are going to see an uptick in cases — and hopefully there is enough background immunity so that we don’t wind up with a lot of hospitalizations,” he said.

Yes, but: Fauci told Bloomberg TV that “it is likely that we will see a surge in the fall.”

• “I would think that we should expect that we are going to see some increase in cases as you get to the colder weather in the fall,” he said.
• “That’s the reason why the (Food and Drug Administration) and their advisory committee are meeting right now to plan a strategy, and we at the (National Institutes of Health) are doing studies now to determine what the best boost would be.”

Flashback: At the end of March, Fauci, the White House medical adviser on the coronavirus, said on ABC’s “This Week” program that he didn’t think there would be a surge from the BA.2 variant, per The Hill.
• “I don’t think we will,” he added. “The easiest way to prevent that is to continue to get people vaccinated. And for those who have been vaccinated, to continue to get them boosted, so that’s really where we stand right now.”
• Fauci also told KGTV he expects “we might see an uptick in cases here in the United States because, only a week or so ago, the CDC came out with their modification of the metrics for what would be recommended for masking indoors, and much of the country right now is in that zone, where masking indoors is not required.”

New Mutant May be More Transmissible: Gurugram Health Dept Issues Guidelines to Monitor XE Covid Variant [India.com, 9 Apr 2022]

An intensive screening campaign will be run in crowded places and the private health facilities will have to update the department if they find any suspicious case of the new variant.

Gurugram: The Gurugram district health department has issued directions for the private and government health facilities to monitor the newly reported Covid cases here in the wake of country’s first case of coronavirus variant XE being reported in Mumbai. Although no cases of the new variant have been reported yet, Gurugram Chief Medical Officer (CMO), Virender Yadav has issued an advisory to all the concerned officials and authorities about the new variant.Also Read - Massive Fire Breaks Out In Slum Cluster In Gurugram's Sector 74, Fire Tenders Rush To Spot

The health officials said that the department has prepared an action plan to deal with the new variant. An intensive screening campaign will be run in crowded places and the private health facilities will have to update the department if they find any suspicious case of the new variant.
The officials said that the new mutant may be more transmissible than any strain of Covid. Also Read - Gurugram Police Arrest 2 For Duping Car Buyers on OLX. Here's What Happened
“We have directed the private health facilities to keep a watch on patients who had foreign travel history and immediately inform the health department. Rapid antigen probe will be emphasised. Necessary directions have been issued to the concerned authorities,” Yadav told IANS. All government and private hospitals have been instructed to take necessary steps to prevent Covid infections, Yadav added. Also Read - Thieves Break Open Private Bank ATM, Walk Away With Rs 13.28 Lakh in Gurugram

Gurugram Covid update
On Friday, the city reported 61 new Covid cases which has increased the total number of active cases in Gurugram to 270. The health department said fewer people are now using face masks which is another reason for the rise in cases. On April 2, the Haryana government had lifted its mask mandate in public spaces and government offices.

Coronavirus Fourth Wave: UN Expresses Caution As large COVID-19 Outbreaks Reported In Asia [India.com, 9 Apr 2022]

by Sanstuti Nath

UN Secretary-General Antonio Guterres called for governments and pharma companies to work together to deliver vaccines to "every person, everywhere".

United Nations: With the threat of the fourth wave of the COVID-19 pandemic looming large, and new variants of the virus emerging every four months on average, UN Secretary-General Antonio Guterres has cautioned that the COVID-19 pandemic is far from over as large outbreaks are spreading in Asia. Guterres has also called for governments and pharma companies to work together to deliver vaccines to “every person, everywhere”.Also Read - You May Soon Get 'Highly Accurate' COVID-19 Test Result In Just 30-second.

In a video message, Guterres said, “We’re seeing 1.5 million new cases each day. Large outbreaks are spreading in Asia. A new wave is sweeping across Europe.” He added that some countries are reporting their highest death rates since the start of the pandemic. Also Read - Covaxin Booster Dose Enhances Antibody Response Against COVID-19 Variants Including Omicron: ICMR Study

He noted that the Omicron variant of the coronavirus is a startling reminder of how quickly COVID-19 can mutate and spread especially in the absence of high vaccination coverage, and rued, “While some high-income countries are preparing for their second booster doses, one-third of humanity remains unvaccinated.” Also Read - Amid XE COVID Variant Scare, Is India Making A Mistake by Lifting COVID Curbs? Experts Explain

“This is a brutal indictment of our deeply unequal world. It’s also a prime breeding ground for new variants more deaths and increased human and economic misery,” he said, adding that the next variant is not a question of if but of when.

“We are far from our target of every country reaching 70 per cent vaccination coverage by the middle of this year. And with new variants emerging every four months on average, time is of the essence,” he said and added that governments and pharmaceutical companies need to work together to deliver vaccines to every person, everywhere not just in wealthy countries.
COVID XE recombinant and its spread

A new strain of the COVID-19 Omicron variant, first detected in the United Kingdom, appears to be more transmissible than previous strains of the virus, the World Health Organization (WHO) had said. The UN health agency last week that the XE recombinant (BA.1-BA.2), was first detected in the United Kingdom on January 19 and more than 600 sequences have been reported and confirmed since.

“Early-day estimates indicate a community growth rate advantage of 10 per cent as compared to BA.2. However, this finding requires further confirmation,” WHO had said. It added that XE belongs to the Omicron variant until significant differences in transmission and disease characteristics, including severity, may be reported.

WHO continues to closely monitor and assess the public health risk associated with recombinant variants, alongside other SARS-CoV-2 variants, and will provide updates as further evidence becomes available.

Status Of COVID-19 Across the globe
The WHO COVID-19 Weekly Epidemiological Update issued this week said that after the increase observed during the first half of March 2022, the number of new COVID-19 cases has decreased for a second consecutive week, with a 16 per cent decline during the week of March 28 through April 3 as compared to the previous week.

The number of new weekly deaths also decreased sharply (-43 per cent) as compared to the previous week, when an artificial spike in deaths was observed. Across the six WHO regions, over nine million new cases and over 26,000 new deaths were reported. All regions reported decreasing trends both in the number of new weekly cases and new weekly deaths. As of April 3, over 489 million cases and over 6 million deaths have been reported globally.

At the country level, the highest number of new weekly cases were reported from South Korea (2,058,375 new cases; a decline of 16 per cent), Germany (1,371,270 new cases; a 13 per cent decrease), France (959,084 new cases; a 13 per cent increase), Vietnam (796,725 new cases; a 29 per cent decline), and Italy (486,695 new cases; a 3 per cent fall).

The highest number of new weekly deaths were reported in the United States of America (4,435 new deaths; a 10 per cent decline), Russia (2,357 new deaths; an 18 per cent decline), South Korea (2,336 new deaths; a 5 per cent decline), Germany (1,592 new deaths; a 5 per cent rise) and Brazil (1,436 new deaths; a 19 per cent fall).

(With agency inputs)