Brazil has enough infection data to analyze Sinovac's COVID-19 vaccine - officials

 Brazil has gathered enough infection data from a late-stage trial of an experimental COVID-19 vaccine developed by China’s Sinovac Biotech and expects to have interim results on its efficiency in early December, trial organizers said on Monday.

Dimas Covas, director of Butantan biomedical research institute that is running the late-stage trial of the Sinovac vaccine in Brazil, said it now has 74 confirmed cases among its trial participants, above the 61 initial milestone set for interim efficiency analysis.

He said an independent committee is likely to release the efficiency results in the first week of December based on its analysis of the data.

The news comes as Britain’s AstraZeneca Plc on Monday joined its U.S. rivals Pfizer and Moderna and Russia in announcing positive results in pivotal trials, raising hopes that the world would soon have successful vaccines to end the pandemic.

Covas said Brazil’s health ministry now has all the information needed to include Coronavac in the national program, while São Paulo Health Secretary Jean Gorinchteyn expected on Monday Brazil’s regulator to approve the use of the Sinovac vaccine, CoronaVac, by January.

João Gabbardo, head of the Sao Paulo’s COVID-19 contingency committee, said at the same event that he expects China’s health regulator to approve Sinovac’s CoronaVac in December, which could hasten approval in Brazil.

The Sinovac vaccine has been promoted by Sao Paulo Governor João Doria, a move which has put him at odds with President Jair Bolsonaro who is a vocal China skeptic.

Bolsonaro has attacked the Chinese vaccine for lacking credibility and it remains unclear whether the federal government will include it in its national inoculation program.

The ministry said on Sunday it planned to sign non-binding letters of intent to buy vaccines from Pfizer Inc, India’s Bharat Biotech, the Russian Direct Investment Fund, Moderna Inc and Janssen, a unit of Johnson & Johnson, but made no mention of Sinovac’s candidate.

https://www.reuters.com/article/us-health-coronavirus-brazil-sinovac/brazil-has-enough-infection-data-to-analyze-sinovacs-covid-19-vaccine-officials-idUSKBN28327C

The Child-Neglect Pandemic

 Last week New York City mayor Bill de Blasio announced that, once again, the nation’s largest public school system would close, in response to spiking Covid-19 infections—throwing hundreds of thousands of children back into remote-learning environments. The human cost of school closures on children cannot be overstated. According to a new report from JAMA Network Open, the American Medical Association’s monthly open-access medical journal, “a total of 24.2 million children aged 5 to 11 attended public schools that were closed during the pandemic, losing a median of 54 days of instruction.” The report also declares that “missed instruction during 2020 could be associated with an estimated 5.53 million years of life lost. This loss in life expectancy was likely to be greater than would have been observed if leaving primary schools open had led to an expansion of the first wave of the pandemic.”

These are not the only concerns. The dramatic drop in reports of child abuse and neglect—more than 50 percent in New York City this spring—is largely the result of teachers not seeing students in person or communicating with them at all in many cases. Teachers account for about a quarter of reports to children’s services; the lack of in-person schooling means that more kids are left in dangerous situations for longer.

What little teachers see via class Zoom meetings is deeply concerning. A few days ago I spoke with M., a first-grade teacher at a Title I elementary school in Northern California. About 97 percent of the kids in her school receive free or reduced-price lunch. They are mostly Hispanic, with some African-American students as well. School has been completely remote since the spring, and there is no sign that it will return to in-person this school year.

In M.’s class of 30, about five kids never log in, though she and her co-teacher reach out regularly to the parents. The district has provided devices to each child but only one hotspot per home, which can rarely support all the kids—not to mention the friends and neighbors who have started to use it for themselves. Another four or five children are in class for the whole day. A number of kids’ parents work the night shift and may not be awake to ensure that their children log in. The remainder pop in and out, though the district gives them credit for being present as long as the parents or students send in one message to the teachers per day. Districts report that a third of their students are absent each day, but the number of kids not receiving any instruction is actually much higher.

The ones M. is most worried about are those home alone all day while their caregivers are out working. A six-year-old she teaches logged in for parent-teacher conferences one evening. She was home alone, lying in her mother’s bed with her mother’s marijuana pipe in her mouth. On other occasions, she has seen parents get fed up. “I hear kids getting hit and crying in the background.”

Some of the children in her class are also living with parents from whom they were previously taken, either due to restraining orders or custody arrangements. Some have communicated their fears to M. While they’re generally not concerned about being home alone—even all day—they are worried about waking up or angering an adult in the house. M. tells me: “I’m asking them to do work but they’re afraid of making any sounds.”

M. has had a number of meetings with her school’s leadership to discuss whether they should call child protective services. “My principal told me I could decide if I should call. If we do make the call,” she said, “we should expect not to see that child again.” M. is having a hard time determining whether to contact the authorities because she worries that a child might be removed into a situation that’s even worse. “I have two kids whom I’ve been really concerned about.” So far she has not called, but the longer she goes without seeing them in person, the worse she fears things will become.

M. sees parents at the end of their rope with children who are always at home. Under normal circumstances, she might refer them to some respite-care options, but during the pandemic, many of those options are restricted to families that need long-term help, not a night off to cool down.

“My union has negotiated that we will be remote to December,” M. says. “And that we won’t start a conversation about going back to school in person until other issues are taken care of.” She ticks off the list with growing frustration: single-payer health care, racial reparations, and more funding for homeless housing are all on the list. “School opening is being held hostage to other issues.”

M. knows that there is real risk to her going back, and that neither she nor the parents trust the school district to figure out sanitation and other Covid protocols—but she worries that the current situation is worse. Remote schooling has pushed these families to the breaking point. “Just imagine how much people are struggling,” she says. They are trying to “manage their jobs with multiple kids at home. They are angry and tired and scared and sad. And all that comes out on these little ones.” She wants to be “empathetic toward the parents, but I also feel like what’s happening to kids isn’t right.”

https://www.city-journal.org/toll-of-remote-schooling-on-vulnerable-kids

NYC synagogue fined $15K for hosting massive, maskless wedding

 That “mazel cough” will cost a lot!

City Hall will levy a $15,000 fine against the Brooklyn synagogue that broke social distancing regulations by hosting thousands at a clandestine wedding for the grandson of a top religious official in the Hasidic community, Mayor Bill de Blasio said late Monday.

Hizzoner announced the fine and summons the day after The Post exposed how thousands packed into the Yetev Lev temple in South Williamsburg on Nov. 8 — dancing and singing at the top of their lungs with nary a mask in sight as they celebrate the nuptials of Yoel Teitelbaum, the grandson of Satmar Grand Rabbi Aaron Teitelbaum.

“That’s just not acceptable, I mean, we’ve been through so much,” de Blasio told New York 1’s Errol Louis during his regular Monday appearance on ‘Inside City Hall.’ “This was amazingly irresponsible, just unacceptable.”

De Blasio said that while it remains unclear just how many people packed 7,000-person capacity Satmar schul in South Williamsburg, it was obvious that the social distancing and mask-wearing measures ordered by city and state officials were blatantly broken.

The Post obtained videos of the crowds and revealed that extensive measures that organizers took to prevent word of the wedding from leaking out to City Hall after officials kiboshed a similar celebration for the grandson of a competing Satmar sect, fearing the mass indoor gathering could fuel a new coronavirus outbreak.

“There appeared to be a real effort to conceal it which is absolutely unacceptable,” de Blasio told Louis. “There will be a summons for $15,000 immediately for that site and there could be additional consequences quite soon as well.”

Enlarge Image

Yetev Lev templeAP Photo/Frank Franklin II

Despite the COVID-19’s awful toll in ultra-Orthodox communities, officials have struggled to convince residents and local businesses to abide by mask rules and social distancing regulations.

In turn, several of those neighborhoods were at the center of the city’s first major coronavirus outbreak this fall, leading Gov. Andrew Cuomo to impose ‘red zone’ shutdown rules over some of the area to try to contain the spread. That triggered raucous protests that turned violent, including attacks on reporters.

In a horrendous irony, the Yetev Lev’s own president, R’Mayer Zelig Rispler, who openly urged Brooklyn’s Orthodox community to abide by coronavirus safety measures, died of COVID-19 last month at age 70.

https://nypost.com/2020/11/23/nyc-synagogue-fined-15k-for-hosting-massive-wedding/

NYC sees six-hour lines for COVID-19 testing ahead of Thanksgiving

 Lines for COVID-19 tests in Manhattan stretched for more than six hours Monday, as New Yorkers rushed to get checked ahead of Thanksgiving.

Outside a CityMD clinic on East 86th Street in the Upper East Side, the line stretched for three blocks, down First Avenue and onto East 85th Street, by early afternoon.

One local couple said they’d been waiting for six hours, part of it in the rain, since 6:45 am — and still had another hour to go.

“We’ve been taking turns going home to put more layers on and use the bathroom,” said John, 34, a tech worker waiting with his girlfriend.

“We’re getting the rapid results test,” he said. “We have to, we’re going to her parents house in New Jersey for Thanksgiving. Her mom is 65 and her dad is 63.”

Others weren’t so prepared for the long, chilly wait.

“I didn’t know it’d be this long,” said Jack, a 21-year-old student who showed up to the urgent care clinic at 11 a.m. — wearing shorts and flip flops.

“Someone is coming down with some pants,” he added.

He had just come from home Wake Forest University in North Carolina and said his mom was “making” him get tested before Turkey Day with his family.

“I’m doing the rapid test to get the negative results before Thanksgiving, we’re having relatives over,” the Upper East Side resident added. “She’s worried.”

The huge crowds lined up even as many medicals experts and officials advise people to stick to their immediate households for the celebration — and that they shouldn’t necessarily rely on a negative test result as a sign that they’re safe.

The Food and Drug Administration says rapid test results “are usually highly accurate, but false positives can happen, especially in areas where very few people have the virus.”

But that wasn’t going to stop California resident Sarabeth — who joined a six-hour-long line at outside another CityMD on West 88th Street after flying to the East Coast to share the holiday with her family in Connecticut.

“My family won’t let me anywhere near them without (a test),” Sarabeth, who works in real estate marketing, told the Post.

“I explained that I could test negative and have it, it doesn’t mean anything really. They don’t care. I’m not allowed in the house without one.”

https://nypost.com/2020/11/23/nyc-sees-six-hour-lines-for-covid-19-testing-ahead-of-thanksgiving/

Wolf: new mitigation efforts to slow spread of COVID-19 in Pennsylvania

 Pennsylvania Gov. Tom Wolf and Secretary of Health Dr. Rachel Levine have announced new targeted mitigation measures to help limit the spread of COVID-19, including a stay-at-home advisory and new gathering limits.

Wolf said Monday that the state is in a dangerous situation, and it's necessary to redouble efforts to keep people safe.

The new measures include limiting indoor events to 500 people and outdoor events to 2,500 people.

The administration is also encouraging residents to limit unnecessary travel and stay at home.

In addition, the state is stepping up efforts to ensure schools are in compliance with safety plans.

“Our collective responsibility continues to be to protect our communities, our health care workers and our most vulnerable Pennsylvanians from COVID-19. That has not changed," Levine said.

Schools

The Wolf Administration is requiring pre-K to 12 public schools in counties that have been in the substantial transmission level for at least two consecutive weeks to commit to safety measures to ensure the safety and well-being of students and educators. If they choose not to, they must move to fully remote learning without all extra-curricular activities. As of Nov. 20, there are 59 counties in the substantial transmission level for at least two consecutive weeks.

Requirements for pre-K through 12th grade public schools in substantial counties for at least two consecutive weeks:

• Schools are mandated to comply with updated protocols if a COVID-19 case is identified in the school building.
• By 5 p.m. Nov. 30, chief school administrators and the governing body president/chair must sign an attestation form stating they have either transitioned to fully remote learning or are complying with the orders if they are conducting any in-person instruction while in the “substantial” range of transmission.
• Those schools that do not sign or comply with an attestation are required to provide only fully remote learning and suspend all extracurricular activities as long as the county remains in the substantial transmission level.

Businesses

The administration is revising and reissuing its orders to protect businesses, customers, and employees. This order will consolidate previous orders and includes reiterating cleaning and social distancing requirements, mandatory telework requirements unless impossible and other safety measures.

• Telework is mandatory unless impossible. Safety measures required for businesses including cleaning, social distancing and masking.
• Online sales and curbside pickup for all shopping are encouraged.

To help with enforcement of existing masking orders in businesses, the administration is introducing liability protection for all businesses that maintain in person operations and are open to the public. Businesses will receive immunity from civil liability only as related to the health secretary's masking order given that individuals and entities are engaged in essential emergency services activities and disaster services activities when enforcing the order.

Gathering limitations

All large indoor and outdoor events and gatherings are reduced until further notice.

To specifically address large crowds, the retail food services industry - including bars, restaurants, and private catered events - must stop alcohol sales for on-site consumption at 5 p.m. Nov. 25 only. Indoor dining may continue, and takeout is encouraged.

Pennsylvanians are advised against gathering with others who are not in the same household.

The new gathering limits are as follows:

Maximum Occupancy	Allowable Indoor Rate
0-2,000 people	10% of Maximum Occupancy
2,001 - 10,000 people	5% of Maximum Occupancy
Over 10,000 people	No events over 500 people

Maximum Occupancy	Allowable Outdoor Rate
0-2,000 people	15% of Maximum Occupancy
2,001 - 10,000 people	10% of Maximum Occupancy
Over 10,000 people	5% of Maximum Occupancy up to 2,500 people

Empowering local government

• The governor and health secretary's orders were issued pursuant to the authority granted to them under the law, and as such they have the force and effect of law. This authority extends to all local enforcement agencies in Pennsylvania. Local law enforcement received guidance on enforcement of the various COVID-19 orders in place from the Pennsylvania State Police through the Pennsylvania Chiefs of Police Association.
• Given the importance of local engagement, the Department of Health has provided recommendations for local municipal leaders, as well as countywide leadership. While statewide mitigation steps are necessary, local leaders can implement their own orders, ordinances, or directives in order to protect health and safety as long as they are stricter than those mandated by the state. Additionally, counties and municipalities are authorized to enforce state law, including orders from the secretary of health or governor.
• Local leaders at all levels of government should exercise their authority and influence to support public health efforts that will protect residents and local economies. When local leaders engage, their constituents understand that they are supported in adopting and sustaining preventive behaviors.
• The Department of Health has established thresholds representing low, moderate or substantial community transmission of COVID-19, and corresponding actions that can be taken by county and municipal leaders. A county’s threshold may change week-by-week as incidence and percent positivity rates rise and fall. Leaders should implement more public health actions rather than fewer if their county is between thresholds. To determine level of community transmission, counties should use the Department of Health’s COVID-19 Early Warning Monitoring System Dashboard. The Department of Health and the Department of Education use the same metrics to recommend instructional models for school leaders.
• Recommendations for each level of community transmission include increased communication, collaborative planning, stricter directives and working with school leaders.

Enforcement

Orders already in place and those announced are all enforceable. Law enforcement and state agencies will be stepping up enforcement efforts, issuing citations and fines, and possibly taking regulatory actions for repeat offenders.

The Wolf Administration is stepping up enforcement on the following orders:

• Out-of-state travel.
• Mask-wearing.
• Business safety, including telework, occupancy, cleaning, social distancing.
• Restaurant mitigation, including occupancy, masking, social distancing, self-certification.
• Gathering limits.
• School attestation and mitigation.
• Orders are enforceable as a disease control measure under the Disease Prevention and Control Law. Citations may be written under the Administrative Code of 1929 71 P. S. § 1409 and/or the Disease Prevention and Control Law of 1955 35 P.S. § 521.20(a). The decision whether to issue a warning or a citation is made on a case-by-case basis and determined by the unique circumstances of each encounter.
• Persons who fail to comply with an order may be fined between $25 and $300 dollars.
• Enforcement agencies include the Pennsylvania State Police, local law enforcement, personnel from the departments of Agriculture and State and Pennsylvania Liquor Control Board stores that interact with visitors.

The Department of Health, with assistance from other agencies, is bolstering its ability to receive and respond to complaints from customers and employees. The department will continue to investigate complaints provided via its web form and plans to use additional staff from other state agencies under the governor’s jurisdiction to process complaints.

Following a complaint about a business, the Department of Health will send a warning letter informing the business of the potential consequences, including fines and closure if the business is not compliant with the mitigation orders. If a business continues to receive complaints, it risks referral to the Pennsylvania State Police or regulatory agencies, further fines and possible closure.

https://www.wgal.com/article/wolf-administration-announces-new-mitigation-efforts-to-help-stop-covid-19-spread-in-pennsylvania/34762001

NYC Unveils Digital Tool to Help Verify Authenticity of Contact Tracers

 Contract tracers are trying to reach more people than ever amid the latest U.S. surge. But how can you tell if the person who calls you is legitimate? New York City now has an answer to that all-important question.

New Yorkers contacted by the city's Test & Trace Corps to track possible COVID-19 exposure can now verify the authenticity of the contact tracer through a brand new digital function of the program, officials announced Friday.

Anyone called or visited at home by a city tracer can now ask for a "validation code" meant to confirm the tracer's identity. A new website feature released by the city now confirms the tracer's identity by simply inputting the code.

Once a code has been used it will no longer be valid, further preventing the possibility of fraud, the program's leaders said.

"Contact tracing is a tried and true public health measure, and this new technology improves upon that practice," Lisa Hendricks, chief technology officer of the corps, said in a press release Friday. "We are taking every step to ensure the safety of our community members."

Phone calls from the Test & Trace Corps begin with 212-540-XXXX or 212-242-XXX. The program's leaders warn New Yorkers not to provide their Social Security number, private financial/credit card information, or control of personal technology equipment; no tracer will ask for the aforementioned access.

"As more people test positive for COVID-19, our contact tracers are reaching more New Yorkers than ever," Dr. Ted Long, executive director of NYC Test & Trace Corps, said in a press release Friday. "Our program has been able to reach 90% of all New Yorkers diagnosed with COVID-19 since our program launched in June, and we are confident that this tool will help us reach even more New Yorkers by earning their trust from the start."

This latest function of the city's corps program follows the expansion of at-home test kits provided to New Yorkers potentially exposed to the virus. Anyone who has been notified by contact tracers that they may have been exposed to COVID-19, will receive a free at-home coronavirus test kit.

Officials also remind New Yorkers that if they need to quarantine separate from their family to reduce spread, the city has a program in place where individuals can quarantine at local hotels free of charge.

https://www.nbcnewyork.com/news/local/nyc-unveils-digital-tool-to-help-new-yorkers-verify-authenticity-of-contact-tracers/2737423/

Why Oxford’s positive COVID vaccine results are puzzling scientists

 A highly anticipated COVID-19 vaccine has delivered some encouraging — but head-scratching — results. The vaccine developed by the University of Oxford, UK, and pharmaceutical giant AstraZeneca was found to be, on average, 70% effective in a preliminary analysis of phase III trial data, the developers announced in a press release on 23 November.

But the analysis found a striking difference in efficacy, depending on the amount of vaccine delivered to a participant. A regimen consisting of two full doses given a month apart looked to be just 62% effective. But, surprisingly, participants who received a lower amount of the vaccine in a first dose and then the full amount in the second dose were 90% less likely to develop COVID, compared with participants in the placebo arm.

Last week, Pfizer and BioNTech reported that their RNA-based vaccine was 95% effective after the trial reached its primary endpoint, and an interim analysis of Moderna’s RNA vaccine showed it worked nearly as well.

Researchers caution against making head-to-head comparisons of vaccines based on incomplete data. The disparity in the latest results mean there is considerable uncertainty in precisely how well the Oxford vaccine protects against COVID-19 without more data from ongoing efficacy trials, say scientists. “We’re slightly in danger of rushing to compare apples and oranges,” says Daniel Altmann, an immunologist at Imperial College London. “There’s a long, long way to go before these data settle down and get reported and published in full.”

Viral vector

The Oxford–AstraZeneca vaccine is made from a cold-causing ‘adenovirus’ that was isolated from the stool of chimpanzees and modified so that it no longer replicates in cells. When injected, the vaccine instructs human cells to produce the SARS-CoV-2 spike protein — the immune system’s main target against coronaviruses.The vaccine entered phase III efficacy trials before other frontrunners, including Pfizer and Moderna, and trials are ongoing in countries including the United States, South Africa, Japan and Russia. The 23 November analysis is based on 131 COVID-19 cases among more than 11,000 trial participants in the United Kingdom and Brazil, up to 4 November.

Overall, the developers found that the two-dose vaccine had an efficacy of 70%, when measured two weeks after participants received their second dose. But that figure is an average of the 62% and 90% efficacy figures from the two different dosing regimens. “90% is pretty good, but the 62% for the second tested regimen are not that impressive,” Florian Krammer, a virologist at a virologist at Icahn School of Medicine at Mount Sinai in New York City said on Twitter.

A top priority for researchers is understanding why the vaccine seems to have performed so much better with a lower first dose. One explanation could lie in the data: the trial might not have been big enough to gauge the difference between the two regimens, and the differences will vanish once more cases of COVID-19 are detected, says Luk Vandenberghe, a virologist at the Massachusetts Eye and Ear Institute and Harvard Medical School in Boston. The more effective ‘half-dose, full dose’ results were based on 2,741 trial participants, whereas the less efficacious arm included 8,895 volunteers. The press release did not specify in which group cases occurred.

Stephen Evans, a statistical epidemiologist at the London School of Hygiene and Tropical Medicine, estimates, based on the data, the group that the ‘half-dose, full dose’ regimen could have an efficacy as low as 66%.

Dosing theories

But, if the differences are bona fide, researchers are eager to understand why. “I don’t think it’s an anomaly,” says Katie Ewer, an immunologist at Oxford’s Jenner Institute who is working on the vaccine. “I’m keen to get into the lab and start thinking about how we address that question.” She has two leading theories for why a lower first dose might have led to better protection against COVID. It’s possible that lower doses of vaccine do a better job at stimulating the subset of immune cells called T cells that support the production of antibodies, she says.

Another potential explanation is the immune system’s response against the chimpanzee virus. The vaccine triggers an immune response not only to the SARS-CoV-2 spike protein, but also to components of the viral vector. It’s possible that the full first dose blunted this reaction, says Ewer. She plans to look at antibody responses against the chimpanzee virus to help address this question.

“This is a plausible explanation,” says James Wilson, a virologist at the University of Pennsylvania in Philadelphia who pioneered the use of adenoviruses for vaccines in the 1990s. By giving a half-dose first, “it is possible that AstraZeneca threaded the needle with their dosing,” he adds.

Hildegund Ertl, a viral immunologist at the Wistar Institute in Philadelphia, says results make sense in the light of some of her work on adenovirus vaccines in mice. She, too, has found that a low first dose can lead to better protection than a higher first dose in a two-dose vaccine. She thinks this is because a lower first dose leads more quickly to the establishment of ‘memory’ immune cells that are triggered by a second-dose boost. Waiting longer between the two doses could achieve the same effect.

Meanwhile, AstraZeneca hopes to gather more data on the dosing regimen. The company has so far given the vaccine to around 10,000 participants in a US arm of the efficacy trial, which was paused for more than a month in the summer while a neurological condition in a trial participant was investigated.

The company plans to ask regulators whether it can modify the trial to include the more efficacious dosing regimen, Mene Pangalos, AstraZeneca’s vice-president of biopharmaceuticals research, said at a press briefing.

“It would be madness to use more vaccine than you needed to get less efficacy,” says Ewer. “I think we will see a move towards rollout of the ‘low dose, standard dose’ regime.”

Hints of optimism

While Oxford and AstraZeneca make sense of their trial data and gather more, there is reason for optimism in other facets of the vaccine’s performance, say scientists. No participants who received the vaccine were hospitalized or developed severe COVID, suggesting the vaccine may do a good job preventing such infections.

There were also hints that the vaccine may prevent people from transmitting the virus, even if they aren’t showing symptoms. In the trial’s UK arm, some participants routinely swabbed themselves for SARS-CoV-2 testing, even if they weren’t showing symptoms. Differences in infection rates between people who received the placebo and the Oxford vaccine suggest the vaccine blocks transmission, says Ewer. (Pfizer and Moderna’s trials tested only people who showed symptoms.)

Even with a question mark hanging over its efficacy, the Oxford–AstraZeneca vaccine may see wider rollout than some other COVID immunizations. The vaccine is stable at refrigerator temperatures, in contrast to Pfizer and BioNtech’s vaccine which must be stored at –70 ºC until hours before vaccination.

And more of the vaccine may be available sooner, relative to other jabs. AstraZeneca estimates that it will have 200 million doses ready worldwide by the end of 2020 and capacity to produce 100 million to 200 million doses per month once production is ramped up, according to Pam Cheng, vice-president for operations and information technology at AstraZeneca.

“The battle really between all these vaccines is going to be really a logistical one,” says Vandenberghe. “We will be able to use every dose that becomes available.”

doi: https://doi.org/10.1038/d41586-020-03326-w

https://www.nature.com/articles/d41586-020-03326-w