Mapping Severe COVID-19 in the Lungs at Single-Cell Resolution

Caption: Image shows macrophages (red), fibroblast cells (green), and other cells (blue). In late COVID-19, macrophages migrate near fibroblasts, which may play a role in fibrosis. Credit: Images courtesy of André Rendeiro

A crucial question for COVID-19 researchers is what causes progression of the initial infection, leading to life-threatening respiratory illness. A good place to look for clues is in the lungs of those COVID-19 patients who’ve tragically lost their lives to acute respiratory distress syndrome (ARDS), in which fluid and cellular infiltrates build up in the lung’s air sacs, called alveoli, keeping them from exchanging oxygen with the bloodstream.

As shown above, a team of NIH-funded researchers has done just that, capturing changes in the lungs over the course of a COVID-19 infection at unprecedented, single-cell resolution. These imaging data add evidence that SARS-CoV-2, the coronavirus that causes COVID-19, primarily infects cells at the surface of the air sacs. Their findings also offer valuable clues for treating the most severe consequences of COVID-19, suggesting that a certain type of scavenging immune cell might be driving the widespread lung inflammation that leads to ARDS.

The findings, published in Nature [1], come from Olivier Elemento and Robert E. Schwartz, Weill Cornell Medicine, New York. They already knew from earlier COVID-19 studies about the body’s own immune response causing the lung inflammation that leads to ARDS. What was missing was an understanding of the precise interplay between immune cells and lung tissue infected with SARS-CoV-2. It also wasn’t clear how the ARDS seen with COVID-19 compared to the ARDS seen in other serious respiratory diseases, including influenza and bacterial pneumonia.

Traditional tissue analysis uses chemical stains or tagged antibodies to label certain proteins and visualize important features in autopsied human tissues. But using these older techniques, it isn’t possible to capture more than a few such proteins at once. To get a more finely detailed view, the researchers used a more advanced technology called imaging mass cytometry [2].

This approach uses a collection of lanthanide metal-tagged antibodies to label simultaneously dozens of molecular markers on cells within tissues. Next, a special laser scans the labeled tissue sections, which vaporizes the heavy metal tags. As the metals are vaporized, their distinct signatures are detected in a mass spectrometer along with their spatial position relative to the laser. The technique makes it possible to map precisely where a diversity of distinct cell types is located in a tissue sample with respect to one another.

In the new study, the researchers applied the method to 19 lung tissue samples from patients who had died of severe COVID-19, acute bacterial pneumonia, or bacterial or influenza-related ARDS. They included 36 markers to differentiate various types of lung and immune cells as well as the SARS-CoV-2 spike protein and molecular signs of immune activation, inflammation, and cell death. For comparison, they also mapped four lung tissue samples from people who had died without lung disease.

Altogether, they captured more than 200 lung tissue maps, representing more than 660,000 cells across all the tissues sampled. Those images showed in all cases that respiratory infection led to a thickening of the walls surrounding alveoli as immune cells entered. They also showed an increase in cell death in infected compared to healthy lungs.

Their maps suggest that what happens in the lungs of COVID-19 patients who die with ARDS isn’t entirely unique. It’s similar to what happens in the lungs of those with other life-threatening respiratory infections who also die with ARDS.

They did, however, reveal a potentially prominent role in COVID-19 for white blood cells called macrophages. The results showed that macrophages are much more abundant in the lungs of severe COVID-19 patients compared to other lung infections.

In late COVID-19, macrophages also increase in the walls of alveoli, where they interact with lung cells known as fibroblasts. This suggests these interactions may play a role in the buildup of damaging fibrous tissue, or scarring, in the alveoli that tends to be seen in severe COVID-19 respiratory infections.

While the virus initiates this life-threatening damage, its progression may not depend on the persistence of the virus, but on an overreaction of the immune system. This may explain why immunomodulatory treatments like dexamethasone can provide benefit to the sickest patients with COVID-19. To learn even more, the researchers are making their data and maps available as a resource for scientists around the world who are busily working to understand this devastating illness and help put an end to the terrible toll caused by this pandemic.

References:

[1] The spatial landscape of lung pathology during COVID-19 progression. Rendeiro AF, Ravichandran H, Bram Y, Chandar V, Kim J, Meydan C, Park J, Foox J, Hether T, Warren S, Kim Y, Reeves J, Salvatore S, Mason CE, Swanson EC, Borczuk AC, Elemento O, Schwartz RE. Nature. 2021 Mar 29.

[2] Mass cytometry imaging for the study of human diseases-applications and data analysis strategies. Baharlou H, Canete NP, Cunningham AL, Harman AN, Patrick E. Front Immunol. 2019 Nov 14;10:2657.

Links:

COVID-19 Research (NIH)

Elemento Lab (Weill Cornell Medicine, New York)

Schwartz Lab (Weill Cornell Medicine)

NIH Support: National Center for Advancing Translational Sciences; National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; National Cancer Institute

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A novel, quick, and easy system for genetic analysis of SARS-CoV-2

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. We know that mutations in the genome of SARS-CoV-2 have occurred and spread, but what effect do those mutations have? Current methods for studying mutations in the SARS-CoV-2 genome are very complicated and time-consuming because coronaviruses have large genomes, but now a team from Osaka University and Hokkaido University have developed a quick, PCR-based reverse genetics system for analyzing SARS-CoV-2 mutations.
This system uses the polymerase chain reaction (PCR) and a circular polymerase extension reaction (CPER) to reconstruct the full-length cDNA of viral genome. This process does not involve the use of bacteria, which can introduce further unwanted mutations, and takes only two weeks using simple steps to generate infectious virus particles. Previous methods took a couple of months and were very complicated procedures.
“This method allows us to quickly examine the biological features of mutations in the SARS-CoV-2,” says lead author of the study Shiho Torii. “We can use the CPER technique to create recombinant viruses with each mutation and examine their biological features in comparison with the parental virus.” The large circular genome of SARS-CoV-2 can be constructed from smaller DNA fragments that can then be made into a viable viral genome with CPER, and used to infect suitable host cells. A large amount of infectious virus particles can be recovered nine days later.
“We believe that our CPER method will contribute to the understanding of the mechanisms underlying propagation and pathogenesis of SARS-CoV-2, as well as help determine the biological significance of emerging mutations,” explains corresponding author Yoshiharu Matsuura. “This could accelerate the development of novel therapeutics and preventative measures for COVID-19.” The team also suggest that the use of the CPER method will allow researchers to insert “reporter genes” into the SARS-CoV-2 genome to “tag” genes or proteins of interest. This will enable a greater understanding of how SARS-CoV-2 infects cells and causes COVID-19, assisting with the development of therapies. The CPER method could even allow a recombinant virus that is unable to cause disease to be generated, which could be used as a safe and effective vaccine for SARS-CoV-2.
Mutations are arising in the SARS-CoV-2 population all the time, as well as questions as to what those mutations do and whether they could affect the efficacy of vaccines. “Our simple and rapid method allows scientists around the globe to characterize the mutants, which is a vital step forward in our fight against the SARS-CoV-2,” says Takasuke Fukuhara of the research group.
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Materials provided by Osaka University. Note: Content may be edited for style and length.

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Scientists identify severe asthma species, show air pollutant as likely contributor

Asthma afflicts more than 300 million people worldwide. The most severe manifestation, known as non-Th2, or non-atopic childhood asthma, represents the majority of the cases, greater than 85%, particularly in low-income countries, according to Hyunok Choi, an associate professor at the Lehigh University College of Health. Yet, whether non-Th2 is a distinct disease (or endotype) or simply a unique set of symptoms (or phenotype) remains unknown.
“Non-Th2 asthma is associated with very poor prognosis in children and great, life-long suffering due to the absence of effective therapies,” says Choi. “There is an urgent need to better understand its mechanistic origin to enable early diagnosis and to stop the progression of the disease before it becomes severe.”
Studies show that nearly 50% of the children whose asthma is poorly controlled are expected to emerge as severe adult cases. Yet, a one-size-fits-all treatment approach, currently the norm for asthma, is ineffective and, says Choi, and partially responsible for asthma’s growing economic burden.
“The primary reason for lack of therapeutic and preventive measures is that no etiologic, or causal, driver has ever been identified for the non-Th2 asthma,” says Choi.
Now, for the first time, an epidemiological study, led by Choi, has shown that not only is non-Th2 a distinct disease, its likely inducer is early childhood exposure to airborne Benzo[a]pyrene, a byproduct of fossil fuel combustion. Choi and her colleagues are the first to demonstrate air pollution as a driver of the most challenging type of asthma, the severe subtype which is non-responsive to current therapies.
The team describes their results in an article recently published online in Environmental Health Journal called “Airborne Benzo[a]Pyrene May Contribute to Divergent Pheno-Endotypes in Children.”
What is termed asthma is an umbrella word for multiple diseases with common symptoms. Asthma has been broadly classified as two major sets of symptoms: T helper cell high (Th2-high) and T helper cell low (non-Th2). Th2-high is associated with early-childhood allergies to common pollutants such as pet dander, tree pollens, or mold. In contrast, non-TH2 is not related to an allergic response. The non-Th2 type, marked explicitly by being non-allergy-related, is far less understood than the TH-2 type and could transform into severe or difficult to treat type.
“The identification of non-Th2 asthma as a distinct disease, with early exposure to Benzo[a]pyrene as a driver, has the potential to impact tens of millions of sufferers, since this would make it possible to intervene before the onset of irreversible respiratory injuries,” says Choi.
The team tested two comparable groups of children from an industrial city, Ostrava, and the surrounding semi-rural area of Southern Bohemia, in the Czech Republic: 194 children with asthma and a control group consisting of 191 children. According to the study, Ostrava is an industrial city with a high level of coal mining activities, coal processing, and metallurgical refinement. The district-level ambient mean for Benzo[a]pyrene at the time of their investigation November 2008) was 11-times higher than the recommended outdoor and indoor air quality standard.
Not only was elevated exposure to Benzo[a]pyrene associated with correspondingly elevated odds of non-Th2 asthma, it was also associated with depressed systemic oxidant levels.
“Contrary to the current body of evidence supporting adult onset of non-atopic asthma, our data suggest for the first time that the lung function deficit and suppressed oxidative stress levels during early childhood are critical sentinel events preceding non-atopic asthma,” says Choi.
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Materials provided by Lehigh University. Original written by Lori Friedman. Note: Content may be edited for style and length.

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Study links structural brain changes to behavioral problems in children who snore

A large study of children has uncovered evidence that behavioral problems in children who snore may be associated with changes in the structure of their brain’s frontal lobe. The findings support early evaluation of children with habitual snoring (snoring three or more nights a week). The research, published in Nature Communications, was supported by the National Institute on Drug Abuse (NIDA) and nine other Institutes, Centers, and Offices of the National Institutes of Health.
Large, population-based studies have established a clear link between snoring and behavioral problems, such as inattention or hyperactivity, but the exact nature of this relationship is not fully understood. While a few small studies have reported a correlation between sleep apnea — when pauses in breathing are prolonged — and certain brain changes, little is known about whether these changes contribute to the behaviors seen in some children with obstructive sleep-disordered breathing (oSDB), a group of conditions commonly associated with snoring that are characterized by resistance to breathing during sleep.
To address this knowledge gap, researchers led by Amal Isaiah, M.D., D.Phil., of the University of Maryland School of Medicine, capitalized on the large and diverse dataset provided by the Adolescent Brain Cognitive Development (ABCD) Study, a long-term study of child health and brain development in the United States. The team of researchers mined this wealth of data from more than 11,000 9- and 10-year-old children to examine the relationships among snoring, brain structure, and behavioral problems.
Confirming the results of previous work, their statistical analysis revealed a positive correlation between habitual snoring and behavioral problems, with the children who most frequently snored generally exhibiting worse behavior according to an assessment completed by parents. The findings further showed that snoring is linked to smaller volumes of multiple regions of the brain’s frontal lobe, an area involved in cognitive functions such as problem solving, impulse control, and social interactions. The statistical analysis also suggested that the brain differences seen in children who snore may contribute to behavioral problems, but additional work on how snoring, brain structure, and behavioral problems change over time is needed to confirm a causal link.
This study’s findings point to oSDB as a potential reversible cause of behavioral problems, suggesting that children routinely be screened for snoring. Children who habitually snore may then be referred for follow-up care. Such care may include assessment and treatment for conditions that contribute to oSDB, such as obesity, or evaluation for surgical removal of the adenoids and tonsils.
The ABCD Study, the largest of its kind in the United States, is tracking nearly 12,000 youth as they grow into young adults. Investigators regularly measure participants’ brain structure and activity using magnetic resonance imaging (MRI) machines, and collect psychological, environmental, and cognitive information, as well as biological samples. The goal of the study is to define standards for normal brain and cognitive development and to identify factors that can enhance or disrupt a young person’s life trajectory.
The Adolescent Brain Cognitive Development Study and ABCD Study are service marks and registered trademarks, respectively, of the U.S. Department of Health and Human Services.
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Covid-19: US agencies call for pause in Johnson & Johnson vaccine

SharecloseShare pageCopy linkAbout sharingimage copyrightReutersUS health authorities are calling for a pause in the use of the Johnson & Johnson Covid-19 vaccine, after reports of extremely rare blood clotting cases.The Food and Drug Administration (FDA) said it was acting “out of an abundance of caution”.It said six cases of severe blood clotting had been detected in more than 6.8 million doses of the vaccine.The recommendation follows similar rare cases in the AstraZeneca vaccine, which has prompted some curbs in its use.In a series of tweets, the FDA said it and the Centers for Disease Control and Prevention (CDC) were reviewing “six reported US cases of a rare & severe type of blood clot in individuals after receiving the vaccine. Right now, these adverse events appear to be extremely rare”.”We are recommending a pause in the use of this vaccine out of an abundance of caution,” it said.This was to “ensure that the health care provider community is aware of the potential for these adverse events”.A joint statement from the FDA and CDC clarified that the blood clotting was cerebral venous sinus thrombosis (CVST).It said that this type of blood clot needed a different treatment than usual.The common treatment – an anticoagulant drug called heparin – “may be dangerous”, it said and an alternative was required.All six cases were in women aged between 18 and 48, with symptoms six to 13 days after vaccination.The New York Times quoted officials as saying one woman had died and a second, in Nebraska, was in a critical condition.Johnson & Johnson statementThe joint statement said that “people who have received the J&J vaccine who develop severe headache, abdominal pain, leg pain, or shortness of breath within three weeks after vaccination should contact their health care provider”.Johnson & Johnson, a US health care company, issued a statement saying that safety was its “number one priority” and that it shared “all adverse event reports” with the health authorities.It added: “We are aware that thromboembolic events including those with thrombocytopenia have been reported with Covid-19 vaccines. At present, no clear causal relationship has been established between these rare events and the Janssen (J&J) Covid-19 vaccine.”It said it would continue to work closely with the regulators.AstraZeneca vaccinationsThe Oxford-AstraZeneca vaccine, which has been given safely to tens of millions of people, has also seen some extremely rare blood clotting cases.The reports led some nations to suspend its use but most have now resumed, although in a number of cases with a recommended minimum age, for example 60 and over in Germany.In the UK, authorities advised that those under 30 should be offered an alternative.

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Covid: People 45 or over in England invited to book vaccine

SharecloseShare pageCopy linkAbout sharingimage copyrightReutersPeople aged 45 or over in England can now get a Covid jab, as the vaccination programme enters the next phase.Appointments can be booked on the NHS England website, which temporarily crashed on Tuesday morning when it opened up to the new age group. It comes after all over-50s and those in high-risk groups in the UK were offered a first dose of the vaccine.Prime Minister Boris Johnson said he could not see any reason to change England’s roadmap out of lockdown.However, he warned that infections and deaths would start to rise again as restrictions were eased.He said that although the vaccination programme had helped reduce the numbers, “the bulk of the work in reducing the disease has been done by the lockdown” and he urged people to be “cautious”.Mr Johnson added that he was “very confident” about the UK’s vaccine supplies. The government is aiming to offer a first dose to all adults by the end of July.When will over-40s get the jab?How many people have been vaccinated so far?UK sets new record for Covid jab second dosesMinisters have met their target of offering a first dose to the top nine priority groups by 15 April. Its has now moved onto “phase 2” of the vaccination programme – which involves offering vaccines to healthy adults under the age of 50. There are an estimated 3.7 million people in England aged 45 to 49.In Northern Ireland, people aged 40-45 are now eligible to get a Covid vaccine, while in some areas in Wales 40-49 year-olds are being invited.More than 32 million people in the UK have had their first vaccine dose.On Saturday a record 475,230 second doses were given out, with more than 7.6 million people now fully vaccinated.’Supply is a key variable for what happens next’Given how quickly the vaccination programme has been rolled out in the UK, hitting the target of all priority groups by mid-April is not unexpected. And remember, there is no published data on the number of people offered jabs, as opposed to those who have actually been vaccinated. However, NHS England has made clear that across the nine groups, 95% have actually had their first doses – that is an average, with take-up rates varying in different groups.Online bookings for the next age group, those aged 45 and over, have opened in England. Text messages to 48 and 49-year-olds from local vaccination centres are set to go out soon. But what’s not known is to what extent supplies of Pfizer and Moderna vaccines will fill the gap caused this month by supply problems with the AstraZeneca doses. The government is sticking to the line that the programme is on track to offer every adult a first dose by late July. But officials qualify it by saying this is “subject to supply” – and that is a key variable.England has joined Wales and Scotland in giving out its first doses of the Moderna jab, the third Covid-19 vaccine to be administered in the UK.Meanwhile, Prof Jeremy Brown, a member of the Joint Committee of Vaccination and Immunisation (JCVI), said people will eventually “have to” mix Covid jabs.He told BBC Radio 4’s Today programme: “It’s practically going to have to be that way because, once you’ve completed a course of, say, the Moderna or Pfizer or the AstraZeneca with two doses, in the future it’s going to be quite difficult to guarantee you get the same type of vaccine again.”So there will be a mix-and-match occurring just by the sort of practicalities of doing a third or fourth vaccination over the next few years.”He added that trials involving mixed vaccine combinations were ongoing.Another member of the JCVI, Prof Adam Finn, welcomed the news that the UK had completed the first phase of its vaccination programme but added: “We’re only halfway up the hill.”He told BBC Breakfast: “We mustn’t take our eye off the task and we’ve got to keep working to get to the top.”Prof Finn said people over 50 who have not been invited for a first dose of the vaccine should make a “gentle enquiry” with their GP.On Monday, the UK recorded 3,568 new coronavirus cases and 13 deaths within 28 days of a positive test. It comes after pub gardens, non-essential shops and hairdressers reopened in England. Northern Ireland’s “stay at home” order also ended on Monday, while in Wales non-essential shops and close-contact services reopened. In Scotland, non-essential shops and hospitality are not due to open until 26 April. Meanwhile, surge testing has been implemented in the Wandsworth and Lambeth areas of south London after a cluster of the South African Covid-19 variant was found. The Department of Health and Social Care called it the “largest surge testing operation to date” following the identification of 44 confirmed and 30 probable cases.LOOK-UP TOOL: How many cases in your area?LOCKDOWN RULES: What are they and when will they end?SOCIAL DISTANCING: How can I meet my friend safely? OXFORD JAB: What is the Oxford-AstraZeneca vaccine?A LIFE CHANGED IN SECONDS: “I’d been living my perfect life”EXTRA-TERRESTRIAL LIFE: Is suggesting evidence of aliens worth jeopardising a career?

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Could the Pandemic Prompt an ‘Epidemic of Loss’ of Women in the Sciences?

Even before the pandemic, many female scientists felt unsupported in their fields. Now, some are hitting a breaking point.Like many women during the pandemic, Alisa Stephens found working from home to be a series of wearying challenges.Dr. Stephens is a biostatistician at the University of Pennsylvania, and the technical and detail-oriented nature of her work requires long uninterrupted stretches of thought. Finding the time and mental space for that work with two young children at home proved to be an impossibility.“That first month was really hard,” she recalled of the lockdown. Her infant daughter’s day care was closed, and her 5-year-old was at home instead of at school. With their nanny unable to come to the house, Dr. Stephens tended to her children all day and worked late into the evening. In the fall, when her daughter was set to begin kindergarten, the schools did not reopen.Things eased once the family could safely bring in a nanny, but there was still little time for the deep thought Dr. Stephens had relied on each morning for her work. Over time, she has adjusted her expectations of herself.“Maybe I’m at 80 percent as opposed to 100 percent, but I can get things done at 80 percent to some extent,” she said. “It’s not great, it’s not my best, but it’s enough for now.”Dr. Stephens is in good company. Several studies have found that women have published fewer papers, led fewer clinical trials and received less recognition for their expertise during the pandemic.Add to that the emotional upheaval and stress of the pandemic, the protests over structural racism, worry about children’s mental health and education, and the lack of time to think or work, and an already unsustainable situation becomes unbearable.“The confluence of all of these factors creates this perfect storm. People are at their breaking point,” said Michelle Cardel, an obesity researcher at the University of Florida. “My big fear is that we are going to have a secondary epidemic of loss, particularly of early career women in STEM.”Female scientists were struggling even before the pandemic. It was not unusual for them to hear that women were not as smart as men, or that a woman who was successful must have received a handout along the way, said Daniela Witten, a biostatistician at the University of Washington in Seattle. Some things are changing, she said, but only with great effort, and at a glacial pace.The career ladder is particularly steep for mothers. Even during maternity leave, they are expected to keep up with lab work, teaching requirements, publications and mentoring of graduate students. When they return to work, most do not have affordable child care.Women in academia often have little recourse when confronted with discrimination. Their institutions sometimes lack the human resources structures common in the business world.Leslie Vosshall, a neuroscientist at Rockefeller University. “The older I get, the more of a window I have onto how this profession really works,” she said.Sarah Blesener for The New York TimesThe path is even rockier for scientists of color, like Dr. Stephens, who encounter other biases in the workplace — in everyday reactions, professional reviews or promotions — and now have to cope with the disproportionate impact of the pandemic on Black and Latino communities.Dr. Stephens said a close friend, also a Black scientist, had five family members who contracted Covid-19.The year has been a “pause” for everyone, Dr. Stephens added, and universities should find a way to help scientists when the pandemic ends — perhaps by adding an extra year to the time allotted to them to earn tenure.Others said while extra time for tenure may help, it will be far from enough.“It’s sort of like if you’re drowning, and the university tells you, ‘Don’t worry if it takes you an extra year to get back to shore,’” Dr. Witten said. “It’s like, ‘Hey, that’s not helpful. I need a flotation device.’”Compounding the frustration are the outdated notions about how to help women in science. But social media has allowed women to share some of those concerns and find allies to organize and call out injustice when they see it, said Jessica Hamerman, an immunologist at the Benaroya Research Institute in Seattle. “People are just much less likely to sit quietly, and listen to biased statements that affect them.”In November, for example, a controversial study on female scientists was published in the influential journal Nature Communications, suggesting that having female mentors would hinder the career of young scientists and recommending that the young women instead seek out men to help them.The response was intense and unforgiving.Hundreds of scientists, male and female, renounced the paper’s flawed methods and conclusions, saying it reinforced outdated stereotypes and neglected to take structural biases in academia into account.“The advice from the paper was basically similar to advice your grandmother may have given you 50 years ago: Get yourself a man who will take care of you, and all will be fine,” Dr. Cardel said.Nearly 7,600 scientists signed a petition calling on the journal to retract the paper — which it did on Dec. 21..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-rqynmc{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.9375rem;line-height:1.25rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-rqynmc{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-rqynmc strong{font-weight:600;}.css-rqynmc em{font-style:italic;}.css-akgeos{margin-bottom:15px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.75rem;line-height:1rem;color:#787878;}@media (min-width:740px){.css-akgeos{font-size:0.8125rem;line-height:1.125rem;}}.css-yoay6m{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}@media (min-width:740px){.css-yoay6m{font-size:1.25rem;line-height:1.4375rem;}}.css-1dg6kl4{margin-top:5px;margin-bottom:15px;}#masthead-bar-one{display:none;}#masthead-bar-one{display:none;}.css-1pd7fgo{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;}@media (min-width:740px){.css-1pd7fgo{padding:20px;width:100%;}}.css-1pd7fgo:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-1pd7fgo{border:none;padding:20px 0 0;border-top:1px solid #121212;}.css-1pd7fgo[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-1pd7fgo[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-1pd7fgo[data-truncated] .css-5gimkt:after{content:’See more’;}.css-1pd7fgo[data-truncated] .css-6mllg9{opacity:1;}.css-1rh1sk1{margin:0 auto;overflow:hidden;}.css-1rh1sk1 strong{font-weight:700;}.css-1rh1sk1 em{font-style:italic;}.css-1rh1sk1 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#ccd9e3;text-decoration-color:#ccd9e3;}.css-1rh1sk1 a:visited{color:#333;-webkit-text-decoration-color:#ccc;text-decoration-color:#ccc;}.css-1rh1sk1 a:hover{-webkit-text-decoration:none;text-decoration:none;}The study arrived at a time when many female scientists were already worried about the pandemic’s effect on their careers, and already on edge and angry with a system that offered them little support.“It’s been an incredibly difficult time to be a woman in science,” said Leslie Vosshall, a neuroscientist at Rockefeller University in New York. “We’re already on the ground, we’re already on our knees — and then the paper just comes and kicks us to say: ‘We have the solution, let’s move the graduate students to a senior man.’”Some people on Twitter suggested that the Nature Communications paper had been retracted because a “feminist mob” had demanded it, but in fact the paper was “a dumpster fire of data,” Dr. Vosshall said.The study was based on flawed assumptions and statistical analysis, according to several statisticians. (The authors of the paper declined to comment.)Dr. Vosshall said she felt compelled to push back because the paper was “dangerous.” Department chairs and deans of medical schools would have used the research to steer graduate students toward male mentors and roll back any progress toward making science more equitable, she said: “The older I get, the more of a window I have onto how this profession really works.”She has applied some of her wisdom to invoke change at Rockefeller University, one of the oldest research institutions in the country.A couple of years ago, Rockefeller University invited the news anchor Rachel Maddow to present a prestigious prize. On her way into the auditorium, Ms. Maddow pointed to a wall adorned with pictures of Lasker Award and Nobel Prize winners — all male — affiliated with the university. At least four women at the university had also won prestigious prizes, but their photographs were not on display.“What’s up with the dude wall?” Ms. Maddow asked. And Dr. Vosshall, who had walked past the wall a thousand times, suddenly saw it differently. She realized it sent the wrong message, overtly or not, to all the high school, undergraduate and graduate students who routinely walked past it.“Once you notice a dude wall, you see them everywhere,” she said. “They’re in every auditorium, every hallway, every departmental office, every conference room.”Rockefeller University eventually agreed to replace the display with one that is more representative of the institution’s history. The pictures were taken down on Nov. 11, Dr. Vosshall announced on Twitter, and will be replaced by a more inclusive set.Departments at Yale University and Brigham and Women’s Hospital in Boston have also reconsidered their dude walls, Dr. Vosshall said. “There are some traditions that should not be perpetuated.”

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Sputnik V: What we know about India's Covid-19 vaccines

SharecloseShare pageCopy linkAbout sharingimage copyrightReutersA third coronavirus vaccine has been approved for use in India amid a deadly second wave of infections.Russia’s Sputnik V has been deemed to be safe, and works in a way similar to the Oxford-AstraZeneca jab which is being made in India as Covishield. Sputnik V gives around 92% protection against Covid-19, late stage trial results published in The Lancet reveal.India has so far given more than 100 million doses of two approved vaccines – Covishield and Covaxin. Sputnik V’s approval came on a day when India overtook Brazil to become the country with the second-highest number of cases globally.With the total case tally of more than 13.5 million cases, India is now only behind the United States which has reported more than 31 million cases. With 13.4 million cases, Brazil is now at number three.The government aims to vaccinate 250 million “priority people” by the end of July. But experts say that the pace of vaccination has been slow and unless the drive is scaled up, the target could be missed.What do we know about Sputnik V?The vaccine, developed by Moscow’s Gamaleya Institute, initially generated some controversy after being rolled out before the final trial data had been released.But scientists say its benefits have now been demonstrated.It uses a cold-type virus, engineered to be harmless, as a carrier to deliver a small fragment of the coronavirus to the body.Safely exposing the body to a part of the virus’s genetic code in this way allows it to recognise the threat and learn to fight it off, without the risk of becoming ill.After being vaccinated, the body starts to produce antibodies especially tailored to the coronavirus.This means that the immune system is primed to fight coronavirus when it encounters it for real.It can be stored at temperatures of between 2 and 8C degrees (a standard fridge is roughly 3-5C degrees) making it easier to transport and store. The Russian Direct Investment Fund (RDIF), which is marketing the vaccine, has signed deals to produce more than 750 million doses of Sputnik V in India with six domestic vaccine makers, according to reports. But it has a different second doseUnlike other similar vaccines, the Sputnik jab uses two slightly different versions of the vaccine for the first and the second dose – given 21 days apart.They both target the coronavirus’s distinctive “spike”, but use different vectors – the neutralised virus that carries the spike to the body.The idea is that using two different formulas boosts the immune system even more than using the same version twice – and may give longer-lasting protection.As well as proving effective, it was also safe with no serious reactions linked to the vaccine during the trial.Some side-effects to a vaccine are expected, but these are usually mild, including a sore arm, tiredness and a bit of a temperature. There were no deaths or serious illnesses in the vaccinated group linked to the jab.As well as Russia, Sputnik V is being used in a number of other places, including Argentina, Palestinian territories, Venezuela, Hungary, UAE and Iran.It will be weeks before Sputnik will be rolled out in India and until then, the country has to make do with Covaxin and Covishield.So what do we know about Covaxin?Covaxin is an inactivated vaccine which means that it is made up of killed coronaviruses, making it safe to be injected into the body. Bharat Biotech, a 24-year-old vaccine maker with a portfolio of 16 vaccines and exports to 123 countries, used a sample of the coronavirus, isolated by India’s National Institute of Virology.When administered, immune cells can still recognise the dead virus, prompting the immune system to make antibodies against the pandemic virus. image copyrightGetty ImagesThe two doses are given four weeks apart. The vaccine can be stored at 2C to 8C.The vaccine has an efficacy rate of 81%, preliminary data from its phase 3 trial shows.India’s regulators gave the vaccine an emergency approval in January while the third phase of the trial was still underway, sparking scepticism and questions from experts.Bharat Biotech says it has a stockpile of 20 million doses of Covaxin, and is aiming to make 700 million doses out of its four facilities in two cities by the end of the year. What was the controversy around Covaxin?It all began when the regulator in January said the vaccine had been approved for “restricted use in emergency situations in public interest as an abundant precaution, in clinical trial mode, especially in the context of infection by mutant strains”. Experts wondered how a vaccine was cleared for emergency use by millions of vulnerable people when its trials were still underway. The All India Drug Action Network at the time said that it was “baffled to understand the scientific logic” to approve “an incompletely studied vaccine”. It said that there were “intense concerns arising from the absence of the efficacy data”.Both the manufacturer and drug regulator had defended Covaxin, saying it was “safe and provides a robust immune response”. Bharat Biotech had said that Indian clinical trial laws allowed “accelerated” authorisation for use of drugs after the second phase of trials for “unmet medical needs of serious and life-threatening diseases in the country”. It had promised to provide efficacy data for the vaccine by February, which it has now done.What about Covishield?The Oxford-AstraZeneca vaccine is being manufactured locally by the Serum Institute of India, the world’s largest vaccine manufacturer. It says it is producing more than 60 million doses a month.The vaccine is made from a weakened version of a common cold virus (known as an adenovirus) from chimpanzees. It has been modified to look more like coronavirus – although it can’t cause illness.image copyrightGetty ImagesWhen the vaccine is injected into a patient, it prompts the immune system to start making antibodies and primes it to attack any coronavirus infection.The jab is administered in two doses given between four and 12 weeks apart. It can be safely stored at temperatures of 2C to 8C and can easily be delivered in existing health care settings such as doctors’ surgeries.The jab developed by Pfizer-BioNTech, which is currently being administered in several countries, must be stored at -70C and can only be moved a limited number of times – a particular challenge in India, where summer temperatures can reach 50C.How effective is Covishield?International clinical trials of the Oxford-AstraZeneca vaccine showed that when people were given a half dose and then a full dose, effectiveness hit 90%.But there was not enough clear data to approve the half-dose, full-dose idea.However, unpublished data suggests that leaving a longer gap between the first and second doses increases the overall effectiveness of the jab – in a sub-group given the vaccine this way it was found to be 70% effective after the first dose.Serum Institute (SII), the Indian maker of the vaccine, says Covishield is “highly effective” and backed by phase III trial data from Brazil and United Kingdom. Clinical trials are a three-phased process to determine whether the vaccine induces good immune responses and whether it causes any unacceptable side-effects. But patients’ rights group, All India Drug Action Network, says its approval has been rushed because the manufacturer has not completed a “bridging study” of the vaccine on Indians. Any other vaccine candidates?The other candidates which are in different stages of trials in India to test safety and efficacy include:ZyCov-Di, being developed by Ahmedabad-based Zydus-CadilaA vaccine being developed by Hyderabad-based Biological E, the first Indian private vaccine-making company, in collaboration with US-based Dynavax and Baylor College of MedicineHGCO19, India’s first mRNA vaccine made by Pune-based Genova in collaboration with Seattle-based HDT Biotech Corporation, using bits of genetic code to cause an immune responseA nasal vaccine by Bharat BioTechA second vaccine being developed by Serum Institute of India and American vaccine development company NovavaxWhich countries are signing up for India’s vaccines?India has shipped 64 million doses of vaccines to 86 countries in Latin America, the Caribbean, Asia and Africa. The recipient countries include UK, Canada, Brazil and Mexico. Both Covishield and Covaxin have been exported – some in the form of “gifts”, others in line with commercial agreements signed between the vaccine makers and the recipient nations, and the rest under the Covax scheme, which is led by the World Health Organization (WHO) and hopes to deliver more than two billion doses to people in 190 countries in less than a year.But in March, India placed a temporary hold on all exports of the Oxford-AstraZeneca vaccine. The government said rising cases meant domestic demand was expected to pick up and so the doses were needed for India’s own rollout.

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The anti-vax movement targeting German children

SharecloseShare pageCopy linkAbout sharingimage copyrightEPAA German anti-lockdown, anti-vaccine movement with links to the far right has recruited hundreds of children into a private online group, reports Jessica Bateman.The girl with the loudspeaker doesn’t look much older than 15. “I’ve spoken at these demonstrations [before],” she says, before launching into a tirade against the German government’s lockdown restrictions and vaccination programme. “They say, ‘We have to lock them up! Have them vaccinated! Only then will they be allowed out again!'” she bellows, adding that she was escorted from her school by police for refusing to comply with restrictions.The girl was speaking at one of a series of demonstrations organised by Querdenken, Germany’s anti-lockdown movement. Roughly translated as “lateral thinkers”, it’s a loose-knit coalition that pushes baseless conspiracy theories – such as the idea masks are deadly or that vaccines will alter your DNA. And YouTube videos like this one, and others of other teenagers speaking at events, are frequently shared on social media.How have children become so heavily involved in a controversial movement? We’ve been investigating a private group for under-18s on the chat app Telegram, run by one of Querdenken’s most popular figures.Who are they?The Querdenken movement first sprung up last summer and gained international notoriety when one of its Berlin demonstrations ended with protestors storming the German parliament. The group claims to have no party political affiliation, but several of its key figures have well-documented far-right connections. Querdenken draws in a range of supporters – not only from the far-right, but a motley crew of hippies, spiritualists and some evangelical Christians. Hundreds arrested in German ‘anti-corona’ protestsWater cannon breaks up Covid protest in BerlinGlobetrotting fake newsIt has spawned a new crop of social media celebrities who push disinformation, sell branded merchandise and solicit donations from their followers. One of these is Samuel Eckert, a former evangelical preacher, who runs a public Telegram channel with more than 120,000 subscribers. image copyrightTelegramAccording to computer scientist Josef Holnburger, who has studied the movement’s rise, it’s one of the most popular Telegram channels in Germany. And Eckert also regularly promotes a second, private channel called “SE Youngsters,” which he says is for children and teenagers aged 10 to 17 – even though the minimum age for using Telegram is 16. On Eckert’s website, there’s a sign-up page and a verification process to ensure the interested child really is under 18. Telegram did not respond to our questions about the group.The Anti-Vax FilesThe Anti-Vax Files: A new series from BBC Trending, on the World Service from 05:30 GMT Saturday. Download the podcast or listen online Inside informationThe BBC spoke to an online activist who gained access to the channel via an insider. He describes an echo chamber of increasingly extreme Covid conspiracy theories, alongside talk of deteriorating mental health, school exclusion and bullying.Our source remains anonymous for safety reasons and goes by the name DatenLiebe (“Data Love”) online. He’s been accessing the group – which has more than 300 members – since last autumn. “What surprised me was that the children were having very casual conversations, they were talking about the weather, or about their pets… like totally undangerous stuff,” he says. “But they are also forwarding content from dangerous Telegram channels, like QAnon.”image copyrightTelegramAccording to DatenLiebe, practically “every type” of anti-vax or anti-Covid conspiracy you can think of is circulating in the group. “They say pretty clearly that they either don’t think that coronavirus exists, or that it’s just the flu,” he says. He also says the members have “a strong distrust in state institutions” and most believe Covid-19 vaccines either don’t work or are more harmful than the disease itself.And he’s also tracked stories of the children’s beliefs causing them trouble in their personal lives. Several members of the group have said that they dropped out of school because they can’t handle the pressure around mask regulations, or have been bullied by their classmates.WATCH: Covid vaccine myths bustedThe unfounded claims about vaccines and fertilityThe vaccine misinformation battle raging in France What is QAnon?We spoke to the mother of two girls who are members of the group. Like her daughters, she also believes Covid-19 is no more dangerous than flu, even though overwhelming evidence indicates it’s both more deadly and can result in long-term health problems.The mother also says she doesn’t plan to take a Covid-19 vaccine. However, she’s adamant that her daughters came to their views independently and aren’t being influenced by her or exploited by Samuel Eckert and the Querdenken movement. “We always taught them to think for themselves,” she says.She says her children changed schools – which she describes as a “traumatic” experience for them – after disputes over masks and their involvement in Querdenken demos.Children as propagandaThe safety of children has long been a powerful narrative in conspiracy theories, from the anti-Semitic “blood libel” which falsely accused Jews of murdering children, to the present day QAnon which claims world leaders are involved in child sex trafficking. At the same time, many parents have legitimate concerns about how lockdown measures, including school closures and social distancing, have affected their children’s mental health and education. Journalist Marc Röhig, from the German magazine Der Spiegel, believes Eckert is trying to exploit these fears. “His main target is concerned parents,” he says. “You can have two narratives. One is to fight for your own freedom… But you can also say, let’s fight for our children and for their future.”image copyrightEPAEckert did not respond to any of our requests for comment. However, he says on his social media accounts that the Telegram group is simply for Covid-sceptic young people to meet and support one another. He’s not shy about using them for his own content, too. He set up a dedicated YouTube channel for videos of their speeches, and the children often appear with him at events or on his video livestreams.While experts say the Querdenken movement doesn’t appear to be getting much bigger, it may be becoming more radical. Officials in the state of Baden Württemberg, in Germany’s south-west, have put the group under surveillance as a potential security threat. And protestors are becoming more extreme in their actions, attacking journalists at demonstrations and even targeting vaccination centres.”I’m really concerned about it, because those are real kids,” says DatenLiebe, the inside source. “And they go to real schools and they feel physical pain from a reality that doesn’t exist.”Listen to The Anti-Vax Files from BBC Trending, on the World Service from 05:30 GMT Saturday. Download the podcast or listen online.

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All UK over-50s now offered first dose of Covid jab

SharecloseShare pageCopy linkAbout sharingimage copyrightPA MediaAll over-50s and those in high-risk groups in the UK have now been offered a first dose of a coronavirus vaccine, the government has announced. It means ministers have met their target of offering a first dose to the top nine priority groups by 15 April. The government said it was on track to offer a first dose to all adults by the end of July, with those in their late 40s expected to be next in England. More than 32 million people in the UK have had their first dose. And on Saturday a record 475,230 second doses were given out, with more than 7.6 million people now fully vaccinated.Under-50s in Northern Ireland have already been asked to book appointments, and more people in the age group in other parts of the UK are now set to get their invitations.When will over-40s get the jab?How many people have been vaccinated so far?UK sets new record for Covid jab second dosesPrime Minister Boris Johnson described the news the vaccination target had been reached as “another hugely significant milestone in our vaccine programme”. “We will now move forward with completing essential second doses and making progress towards our target of offering all adults a vaccine by the end of July.”Health Secretary Matt Hancock said: “I’m delighted the team have done such an amazing job to hit yet another target early.”The tide of this pandemic is turning in every part of the UK, as every day more and more people are being given the safety of a Covid-19 vaccine.” ‘Supply is a key variable for what happens next’Given how quickly the vaccination programme has been rolled out in the UK, hitting the target of all priority groups by mid-April is not unexpected. And remember, there is no published data on the number of people offered jabs, as opposed to those who have actually been vaccinated. However, NHS England has made clear that across the nine groups, 95% have actually had their first doses – that is an average, with take-up rates varying in different groups.The key question is: where next? Pending the advice of the Joint Committee on Vaccination and Immunisation, ministers seem set to give the all-clear for invitations to go out to people in their late 40s. But what’s not known is to what extent supplies of Pfizer and Moderna vaccines will fill the gap caused this month by supply problems with the AstraZeneca doses. The government is sticking to the line that the programme is on track to offer every adult a first dose by late July. But officials qualify it by saying this is “subject to supply” – and that is a key variable.Urging those who are eligible to come forward for the jab, he added: “Vaccines are safe and effective and have already saved more than 10,000 lives. “The vaccine programme has had a significant impact on reducing the pressure on hospitals, helping us to gradually ease restrictions.”Sir Simon Stevens, chief executive of NHS England, said it was an “incredible achievement” to have vaccinated 19 out of 20 people aged over-50 with a first dose.He said the vaccination programme was “without a doubt the most successful in our history”, adding: “It’s one of our tickets out of this pandemic and offers real hope for the future.”The announcement came on the day lockdown restrictions were further eased across the UK.Chris Hopson, chief executive of NHS Providers, representing NHS Trusts, urged people offered a vaccine to take it up, saying: “As we return to pub gardens and sports activities and make our way back to non-essential shops, we must continue do all that we can to prevent the spread of infection and ensure this lockdown will be the last.”The top nine priority groups include all over-50s, over-16s with underlying health conditions, unpaid carers for the elderly and disabled and health and social care workers. It covers 99% of those at high risk of dying with Covid-19.The vaccination roll-out will move on to focus on those aged 40-49.The Joint Committee on Vaccination and Immunisation (JCVI), which advises UK health departments, is expected to publish its final advice on how the government should vaccinate under-50s, and the next phase of the programme is expected to begin this week.NHS organisations in the four nations, in collaboration with devolved administrations, will decide how to carry out the JCVI advice. Last week the Moderna vaccine became the third vaccine to be administered in the UK, alongside the Pfizer-BioNTech and the Oxford-AstraZeneca jabs. The roll-out began in Wales, followed by Scotland, and is expected to be delivered in England next.All under-30s in the UK are to be offered an alternative Covid vaccine to the AstraZeneca jab due to the evidence linking it to rare blood clots.On Monday, the UK recorded 3,568 new coronavirus cases and 13 deaths within 28 days of a positive test. It comes after pub gardens, non-essential shops and hairdressers reopened in England. Northern Ireland’s “stay at home” order also ended on Monday, while in Wales non-essential shops and close-contact services reopened. In Scotland, non-essential shops and hospitality are not due to open until 26 April. Meanwhile, surge testing has been implemented in the Wandsworth and Lambeth areas of south London after a cluster of the South African Covid-19 variant was found. The Department of Health and Social Care called it the “largest surge testing operation to date” following the identification of 44 confirmed and 30 probable cases.LOOK-UP TOOL: How many cases in your area?LOCKDOWN RULES: What are they and when will they end?SOCIAL DISTANCING: How can I meet my friend safely? OXFORD JAB: What is the Oxford-AstraZeneca vaccine?A LIFE CHANGED IN SECONDS: “I’d been living my perfect life”EXTRA-TERRESTRIAL LIFE: Is suggesting evidence of aliens worth jeopardising a career?

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