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Published1 day agoShareclose panelShare pageCopy linkAbout sharingImage source, WU HAO/EPA-EFE/REX/ShutterstockChina has reported 60,000 Covid-related deaths in just over a month, the first major death toll released since the country stopped its zero-Covid policy. China has been widely accused of underreporting coronavirus deaths, despite evidence of hospitals and crematoriums being overrun. According to officials, China recorded 59,938 Covid-related deaths between 8 December and 12 January. Most of those who died were over 80, with most having underlying conditions.The figures, include 5,503 deaths caused by respiratory failure directly due to the virus, and 54,435 caused by underlying conditions combined with the virus. The real total is likely to be higher because which the figures refer only to deaths recorded at medical facilities.Image source, Tingshu Wang/ReutersLast month, Beijing changed the way it categorises Covid deaths, only counting towards its total those who died of respiratory failure directly induced by the virus.The World Health Organisation criticised the definition, describing it as “too narrow”.Beijing has always contended that its figures are accurate, calling on the WHO to “uphold a scientific, objective and just position”. Officials said that the peak of patients hospitalised with severe Covid was in early January, although the number subsequently remained high. They said that they would continue to monitor the situation in rural areas, focusing on early detection and prioritising treatment of the most vulnerable. More on this storyChina abandons key parts of zero-Covid strategy7 December 2022

The first time Reneé Jones overdosed on drugs last year, she was at her daughter’s Bronx apartment and had gotten up to get one of her seven grandchildren a cup of water. The next thing she knew, a paramedic was jolting her back to life with a defibrillator.The two that followed happened at a busy plaza in the South Bronx. Both times, Ms. Jones recovered quickly after a squirt of naloxone up her nose. She carries strips to detect the presence of fentanyl in the heroin she takes, but she does not use them. They take time.“When you’re out here in the street and you want to just use your heroin, you don’t want to do all of that,” said Ms. Jones, 57, who first used the drug more than four decades ago and wonders how many more years she has left. “There’s so much fentanyl going around, and I don’t want to be the next one,” she said.Driven by fentanyl’s prevalence and the pandemic’s isolation and despair, drug overdose deaths have soared in New York City, reaching their highest point since the health department began tracking them more than two decades ago.Rachel Arana, a volunteer, handed out food hygiene kits and clean syringes in the Bronx this week. Victor J. Blue for The New York TimesThere were 2,668 fatal overdoses in the city in 2021, according to data released this week. That was an increase of more than 500 over the 2020 figure, which itself was 600 deaths above the total in 2019.In an interview on Friday, the city’s health commissioner, Dr. Ashwin Vasan, said that the number of overdose deaths last year was likely to set another record, although the data was still being compiled from post-mortem toxicology testing.“It does appear we’re on the same trajectory of increase, which is really concerning,” Dr. Vasan said.The new data underscores a grim reality: that the surge seen during the isolation and anxiety of 2020, the pandemic’s first year, was no anomaly.But the toll, Dr. Vasan said, had been overshadowed by other public health crises, such as Covid-19 and then the spread of the Mpox virus last summer.“If it weren’t for the infectious diseases we’ve been challenged by, this would be the No. 1 public health issue,” Dr. Vasan said. “You never want to see an epidemic move in this direction.”Mitzi Gonzales, a volunteer, collected used syringes from a sidewalk in the Mott Haven section of the Bronx.Victor J. Blue for The New York TimesOverdose deaths rose even as officials tried new harm-reduction tactics, and expanded the use of older ones. The city distributes, on average, about 586 naloxone kits each day, reversing countless overdoses in the process. It has given away tens of thousands of fentanyl test strips, allowing users to discover whether their drugs unexpectedly contain the deadly ingredient, which is many times stronger than heroin. And at a couple of locations, users can have drug samples tested for fentanyl concentration, allowing them to more accurately gauge risk and adjust how much to put in a syringe.The biggest development in anti-overdose initiatives are the two supervised injection sites that the city authorized in late 2021, the first such sites to be officially opened in the United States.Staff members at the sites, in the Manhattan neighborhoods of East Harlem and Washington Heights, provide needles and can administer naloxone if needed. Users bring their own drugs to smoke, sniff or inject while seated at a small, well-lit desk that health workers call “a narcotic consumption booth.”The number of deaths the sites may have prevented is difficult to measure, but health officials said that on some 670 occasions, employees at the sites have intervened to reduce the risk of overdose. In some instances, that meant administering naloxone or oxygen or calling for an ambulance to avoid what otherwise would have been overdoses in apartments, parks and elsewhere.Although some drug users are wary of the injection sites, about 2,200 people took advantage of them.One regular client, a 57-year-old retired electrician from Queens, shuffled out of the East Harlem site Friday afternoon with the help of a walker.He said he had just shot two bags of dope, much less than he once would have used. But he suspected that what he had taken was mostly fentanyl. He asked to remain anonymous because he was on probation.Fentanyl was detected in 80 percent of all overdose deaths in 2021, according to the health department report. About 40 percent involved fentanyl and cocaine.A new danger also emerged: xylazine, an animal tranquilizer known as “tranq” and “zombie drug” that is sometimes added to fentanyl to devastating effect, including wounds that can require amputation.Post-mortem testing by the city’s medical examiner in 2021 indicated that 429 of the people who died of an overdose had xylazine in their system. In 2020, xylazine was detected in just 52 such deaths.The health department report released this week said that officials were working with nonprofit organizations “to explore the possibility of expanding” injection sites beyond the first two to other parts of the city, particularly the Bronx.The city’s highest rates of fatal overdoses are in the borough, with South Bronx neighborhoods like Hunts Point and Mott Haven experiencing three times the citywide average.Ms. Arana spoke with Luis Colon in Mott Haven this week. Victor J. Blue for The New York TimesThe overdose death rate is highest among New Yorkers 55 to 64, a reflection most likely of fentanyl’s effect on older, longtime heroin users.In The Hub, an area where four streets converge in what was labeled the Times Square of the Bronx, several opioid users accepted ham-and-cheese sandwiches from outreach workers early Friday while taking stock of the death toll.One of them, Luis Colon, 49, ripped a hole into his sandwich bag with a thumb. He had switched to snorting heroin, often laced with fentanyl, because of an infection in his right arm that he believed had been caused by injecting drugs. Six of his friends had been killed by fentanyl, he said.“I know New York is helping a lot of people with a lot of things, but they got to step their game up,” Mr. Colon said.Ms. Jones, who overdosed three times last year, stood next to him.Dressed in a red windbreaker and tie-dye tights, she referred to herself as the “grandmother” of the little South Bronx plaza where she was standing, often checking on other addicts to make sure they were not convulsing.She had quit using for a time in 2020, but it did not last.“When I sit around people that are getting high and I’m clean,” she said, “I feel like the outcast.”

An uptick hinted at in surveillance data was a mirage, the officials said.Fears that the Covid booster shots made by Pfizer-BioNTech may increase the risk of strokes in people aged 65 and older were not borne out by an intensive scientific investigation, federal officials said on Friday.“It is very unlikely” that the risk is real, the officials said. They urged Americans 6 months and older to continue getting booster shots. Federal officials decided to disclose the concern and the results of their investigation despite worries that the revelation might fuel anti-vaccine sentiment.“We believe it is important to share this information with the public,” a joint statement from the Centers for Disease Control and Prevention and the Food and Drug Administration said.Officials declined requests to discuss details of their investigation.The bivalent vaccine is designed to thwart the original version of the coronavirus as well as versions of the Omicron variant that were circulating in the United States in the summer. The bivalent vaccines made by Pfizer-BioNTech and Moderna are the only boosters available in the United States now, and scientists are engaged in a heated debate over their usefulness compared with the original vaccines.It is unclear whether the new reassurance will prompt Americans to receive a bivalent shot if they have not already done so. Only 39 percent of adults aged 65 and older, and only 16 percent of those aged 5 and older, have so far received a bivalent booster shot.More on the Coronavirus PandemicNew Subvariant: A highly contagious version of the Omicron variant — known officially as XBB.1.5 or by its subvariant nickname, Kraken — is quickly spreading in the United States.Travel: The European Union advised its 27 member nations to require negative Covid-19 tests for travelers boarding flights from China to the region, amid a surge in coronavirus cases in the country.Misinformation: As Covid cases and deaths rise in parts of the United States, misleading claims continue to spread, exasperating overburdened doctors and evading content moderators.Free at-Home Tests: With cases on the rise, the Biden administration restarted a program that has provided hundreds of millions of tests through the Postal Service.The concerns about a possible link to ischemic strokes — which can interrupt blood supply to the brain — first emerged late last year. Data from the Vaccine Safety Datalink, a federal safety surveillance system, hinted that Americans aged 65 and older might be at increased risk of an ischemic stroke in the 21 days after receiving a Pfizer-BioNTech bivalent shot.That signal was specific to the bivalent vaccine made by Pfizer-BioNTech. No similar concerns were linked to the original Covid vaccines or to Moderna’s bivalent boosters.The data prompted federal officials to comb through other vaccine safety databases, as well as observations from the United States and other countries. The investigators did not find evidence of an increased risk of strokes in any of these sources, federal officials said in their statement.Federal officials plan to discuss the findings on Jan. 26 at a meeting of scientific advisers to the F.D.A. on future Covid vaccines.The Vaccine Safety Datalink is a real-time surveillance system, a collaboration between the C.D.C. and integrated health care organizations and networks across the United States. The system uses electronic health data from about a dozen sites in the nation to monitor vaccine safety.Among about 550,000 people aged 65 and older who had received the Pfizer-BioNTech bivalent booster, 130 had ischemic strokes in the 21 days after receiving the shot, raising fears that the two events were related. But analysis of the data using a different method did not reveal an increased risk of ischemic stroke.Another database, the Vaccine Adverse Event Reporting System, managed by the C.D.C. and the F.D.A., also did not pick up a signal for ischemic strokes. Neither did a large study of the bivalent vaccines relying on data from the Centers for Medicare and Medicaid Services, a preliminary study using the Veterans Affairs database, nor Pfizer-BioNTech’s global safety database.Other countries have not observed an increased risk for ischemic stroke with the bivalent vaccines, the agencies said. About 795,000 strokes are reported in the United States each year, and about 87 percent of those are ischemic strokes, according to the C.D.C.“There is no evidence to conclude that ischemic stroke is associated with the use of the companies’ Covid-19 vaccines,” Pfizer and BioNTech said in a statement. More than 30 million doses of the companies’ bivalent vaccine have been administered in the United States so far, according to a spokesman for Pfizer.“Compared to published incidence rates of ischemic stroke in this older population, the companies to date have observed a lower number of reported ischemic strokes” after the bivalent shot, the companies said.

Targeting iron metabolism in immune system cells may offer a new approach for treating systemic lupus erythematosus (SLE) — the most common form of the chronic autoimmune disease lupus.
A multidisciplinary team of investigators at Vanderbilt University Medical Center has discovered that blocking an iron uptake receptor reduces disease pathology and promotes the activity of anti-inflammatory regulatory T cells in a mouse model of SLE. The findings were published Jan. 13 in the journal Science Immunology.
Lupus, including SLE, occurs when the immune system attacks a person’s own healthy tissues, causing pain, inflammation and tissue damage. Lupus most commonly affects skin, joints, brain, lungs, kidneys and blood vessels. About 1.5 million Americans and 5 million people worldwide have a form of lupus, according to the Lupus Foundation of America.
Treatments for lupus aim to control symptoms, reduce immune system attack of tissues, and protect organs from damage. Only one targeted biologic agent has been approved for treating SLE, belimumab in 2011.
“It has been a real challenge to come up with new therapies for lupus,” said Jeffrey Rathmell, PhD, professor of Pathology, Microbiology and Immunology and Cornelius Vanderbilt Chair in Immunobiology. “The patient population and the disease are heterogeneous, which makes it difficult to design and conduct clinical trials.”
Rathmell’s group has had a long-standing interest in lupus as part of a broader effort to understand mechanisms of autoimmunity.

When postdoctoral fellow Kelsey Voss, PhD, began studying T cell metabolism in lupus, she noticed that iron appeared to be a “common denominator in many of the problems in T cells,” she said. She was also intrigued by the finding that T cells from patients with lupus have high iron levels, even though patients are often anemic.
“It was not clear why the T cells were high in iron, or what that meant,” said Voss, first author of the Science Immunology paper.
To explore T cell iron metabolism in lupus, Voss and Rathmell drew on the expertise of other investigators at VUMC: Eric Skaar, PhD, and his team are experienced in the study of iron and other metals; Amy Major, PhD, and her group provided a mouse model of SLE; and Michelle Ormseth, MD, MSCI, and her team recruited patients with SLE to provide blood samples.

First, Voss used a CRISPR genome editing screen to evaluate iron-handling genes in T cells. She identified the transferrin receptor, which imports iron into cells, as critical for inflammatory T cells and inhibitory for anti-inflammatory regulatory T cells.
The researchers found that the transferrin receptor was more highly expressed on T cells from SLE-prone mice and T cells from patients with SLE, which caused the cells to accumulate too much iron.
“We see a lot of complications coming from that — the mitochondria don’t function properly, and other signaling pathways are altered,” Voss said.
An antibody that blocks the transferrin receptor reduced intracellular iron levels, inhibited inflammatory T cell activity, and enhanced regulatory T cell activity. Treatment of SLE-prone mice with the antibody reduced kidney and liver pathology and increased production of the anti-inflammatory factor, IL-10.
“It was really surprising and exciting to find different effects of the transferrin receptor in different types of T cells,” Voss said. “If you’re trying to target an autoimmune disease by affecting T cell function, you want to inhibit inflammatory T cells but not harm regulatory T cells. That’s exactly what targeting the transferrin receptor did.”
In T cells from patients with lupus, expression of the transferrin receptor correlated with disease severity, and blocking the receptor in vitro enhanced production of IL-10.
The researchers are interested in developing transferrin receptor antibodies that bind specifically to T cells, to avoid any potential off-target effects (the transferrin receptor mediates iron uptake in many cell types). They are also interested in studying the details of their unexpected discovery that blocking the transferrin receptor enhances regulatory T cell activity.
Skaar is the Ernest W. Goodpasture Professor of Pathology and director of the Vanderbilt Institute for Infection, Immunology, and Inflammation. Major, associate professor of Medicine, and Ormseth, assistant professor of Medicine, are faculty members in the Division of Rheumatology and Immunology. Rathmell is the director of the Vanderbilt Center for Immunobiology.
Other authors of the study include Allison Sewell, Evan Krystofiak, PhD, Katherine Gibson-Corley, DVM, PhD, Arissa Young, MD, Jacob Basham, MD, Ayaka Sugiura, PhD, Emily Arner, PhD, William Beavers, PhD, Dillon Kunkle, PhD, Megan Dickson, Gabriel Needle, and W. Kimryn Rathmell, MD, PhD.
The research was supported by the National Institutes of Health (grants DK105550, AI153167, DK101003, AI150701, CA253718) and the Lupus Research Alliance William Paul Distinguished Innovator Award to Jeffrey Rathmell.

When genes are activated and expressed, they show patterns in cells that are similar in type and function across tissues and organs. Discovering these patterns improves our understanding of cells — which has implications for unveiling disease mechanisms.
The advent of spatial transcriptomics technologies has allowed researchers to observe gene expression in their spatial context across entire tissue samples. But new computational methods are needed to make sense of this data and help identify and understand these gene expression patterns.
A research team led by Jian Ma, the Ray and Stephanie Lane Professor of Computational Biology in Carnegie Mellon University’s School of Computer Science, has developed a machine learning tool to fill this gap. Their paper on the method, called SPICEMIX, appeared as the cover story in the most recent issue of Nature Genetics.
SPICEMIX helps researchers untangle the role different spatial patterns play in the overall gene expression of cells in complex tissues like the brain. It does so by representing each pattern with spatial metagenes — groups of genes that may be connected to a specific biological process and can display smooth or sporadic patterns across tissue.
The team, which included Ma; Benjamin Chidester, a project scientist in the Computational Biology Department; and Ph.D. students Tianming Zhou and Shahul Alam, used SPICEMIX to analyze spatial transcriptomics data from brain regions in mice and humans. They leveraged the unique capabilities of SPICEMIX to uncover the landscape of the brain’s cell types and spatial patterns.
“We were inspired by cooking when we chose the name,” Chidester said. “You can make all sorts of different flavors with the same set of spices. Cells may work in a similar way. They may use a common set of biological processes, but the specific combination they use gives them their unique identity.”
When applied to brain tissues, SPICEMIX identified spatial patterns of cell types in the brain more accurately than other methods. It also uncovered new expression patterns of brain cell types through the learned spatial metagenes.
“These findings may help us paint a more complete picture of the complexity of brain cell types,” Zhou said.
The number of studies using spatial transcriptomics technologies is growing rapidly, and SPICEMIX can help researchers make the most of this high-volume, high-dimensional data.
“Our method has the potential to advance spatial transcriptomics research and contribute to a deeper understanding of both basic biology and disease progression in complex tissues,” Ma said.

Chemicals that accumulate in the vagina, potentially originating from personal care products, may contribute to spontaneous preterm birth, according to a new study by researchers at Columbia University Vagelos College of Physicians and Surgeons.
The study of 232 pregnant women found that a handful of non-biological chemicals previously found in cosmetics and hygiene products are strongly associated with preterm birth.
“Our findings suggest that we need to look more closely at whether common environmental exposures are in fact causing preterm births and, if so, where these exposures are coming from,” says study co-leader Tal Korem, PhD, assistant professor in the Program for Mathematical Genomics and the Departments of Systems Biology and Obstetrics and Gynecology at Columbia. “The good news is that if these chemicals are to blame, it may be possible to limit these potentially harmful exposures.”
The study was published January 12 in Nature Microbiology.
Preterm birth, childbirth before 37 weeks of pregnancy, is the number one cause of neonatal death and can lead to a variety of lifelong health issues. Two-thirds of preterm births occur spontaneously, but despite extensive research, there are no methods for predicting or preventing spontaneous preterm birth.
Several studies have suggested that imbalances in the vaginal microbiome play a role in preterm birth and other problems during pregnancy. However, researchers have not been able to reproducibly link specific populations of microorganisms with adverse pregnancy outcomes.

The research team, co-led by Korem and Maayan Levy, PhD, of the University of Pennsylvania, decided to take a more expansive view of the vaginal microenvironment by looking at its metabolome. The metabolome is the complete set of small molecules found in a particular biological niche, including metabolites produced by local cells and microorganisms and molecules that come from external sources. “The metabolome can be seen as a functional readout of the ecosystem as a whole,” Korem says. “Microbiome profiling can tell us who the microbes are; metabolomics gets us close to understanding what the microbes are doing.”
In the current study, the researchers measured over 700 different metabolites in the second-trimester metabolome of 232 pregnant women, including 80 pregnancies that ended prematurely.
The study found multiple metabolites that were significantly higher in women who had delivered early than in those who delivered at full term.
“Several of these metabolites are chemicals that are not produced by humans or microbes — what we call xenobiotics,” says Korem. “These include diethanolamine, ethyl-beta glucoside, tartrate, and ethylenediaminetetraacetic acid. While we did not identify the source of these xenobiotics in our participants, all could be found in cosmetics and hygiene products.”
Algorithm predicts preterm birth
Using machine learning models, the team also developed an algorithm based on metabolite levels that can predict preterm birth with good accuracy, potentially paving the way for early diagnostics.

Though the predictions were more accurate than models based on microbiome data and maternal characteristics (such as age, BMI, race, preterm birth history, and prior births), the new model still needs improvement and further validation before it could be used in the clinic.
Despite the current limitations, Korem says, “our results demonstrate that vaginal metabolites have the potential to predict, months in advance, which women are likely to deliver early.”
More information
The first three authors of the paper — William F. Kindschuh (MD/PhD student at Columbia), Federico Baldini (postdoctoral fellow at Columbia), and Martin C. Liu (MS graduate at Columbia) — contributed equally to the research.
The study is titled, “Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome.”
The other contributors are: Jingqiu Liao (Columbia), Yoli Meydan (Columbia), Harry H. Lee (Columbia), Almut Heinken (University of Galway), Ines Thiele (University of Galway and University College Cork, Ireland), and Christoph A. Thaiss (University of Pennsylvania).
The study was supported by grants from National Institute of Nursing Research (R01NR014784), the Center for Precision Medicine at the University of Pennsylvania, the Vagelos Award provided by Columbia University Precision Medicine Initiative, the Program for Mathematical Genomics at Columbia University, and the CIFAR Azrieli Global Scholarship in the Humans & the Microbiome Program.
Maayan Levy and Tal Korem are inventors on a provisional patent application related to this work. The other authors declare no conflict of interests.

Using artificial intelligence, Cornell University engineers have simplified and reinforced models that accurately calculate the fine particulate matter (PM2.5) — the soot, dust and exhaust emitted by trucks and cars that get into human lungs — contained in urban air pollution.
Now, city planners and government health officials can obtain a more precise accounting about the well-being of urban dwellers and the air they breathe, from new research published December 2022 in the journal Transportation Research Part D.
“Infrastructure determines our living environment, our exposure,” said senior author Oliver Gao, the Howard Simpson Professor of Civil and Environmental Engineering in the College of Engineering at Cornell University. “Air pollution impact due to transportation — put out as exhaust from the cars and trucks that drive on our streets — is very complicated. Our infrastructure, transportation and energy policies are going to impact air pollution and hence public health.”
Previous methods to gauge air pollution were cumbersome and reliant on extraordinary amounts of data points. “Older models to calculate particulate matter were computationally and mechanically consuming and complex,” said Gao, a faculty fellow at the Cornell Atkinson Center for Sustainability. “But if you develop an easily accessible data model, with the help of artificial intelligence filling in some of the blanks, you can have an accurate model at a local scale.”
Lead author Salil Desai and visiting scientist Mohammad Tayarani, together with Gao, published “Developing Machine Learning Models for Hyperlocal Traffic Related Particulate Matter Concentration Mapping,” to offer a leaner, less data-intensive method for making accurate models.
Ambient air pollution is a leading cause of premature death around the world. Globally, more than 4.2 million annual fatalities — in the form of cardiovascular disease, ischemic heart disease, stroke and lung cancer — were attributed to air pollution in 2015, according to a Lancet study cited in the Cornell research.
In this work, the group developed four machine learning models for traffic-related particulate matter concentrations in data gathered in New York City’s five boroughs, which have a combined population of 8.2 million people and a daily-vehicle miles traveled of 55 million miles.
The equations use few inputs such as traffic data, topology and meteorology in an AI algorithm to learn simulations for a wide range of traffic-related, air-pollution concentration scenarios.
Their best performing model was the Convolutional Long Short-term Memory, or ConvLSTM, which trained the algorithm to predict many spatially correlated observations.
“Our data-driven approach — mainly based on vehicle emission data — requires considerably fewer modeling steps,” Desai said. Instead of focusing on stationary locations, the method provides a high-resolution estimation of the city street pollution surface. Higher resolution can help transportation and epidemiology studies assess health, environmental justice and air quality impacts.
Funding for this research came from the U.S. Department of Transportation’s University Transportation Centers Program and Cornell Atkinson.

Scientists from the Institut Pasteur, Université Paris Cité, the CNRS and the Collège de France have used paleogenomics to trace 10,000 years of human immune system evolution. They analyzed the genomes of more than 2,800 individuals who lived in Europe over the past ten millennia. They were able to date the increase in frequency of most of the mutations that are advantageous in defending against pathogens to after the Bronze Age, 4,500 years ago. The scientists also observed that mutations conferring a higher risk of developing inflammatory disorders have become more frequent over the past 10,000 years. These enlightening results on the effects of natural selection on immunity genes were published in the journal Cell Genomics on January 13, 2023.
In the 1950s, the geneticist J.B.S. Haldane attributed the maintenance or persistence of the mutation responsible for anomalies in red blood cells commonly observed in Africa to the protection these anomalies provided against malaria, an endemic infection that claims millions of lives. This theory suggested that pathogens are among the strongest selective pressures faced by humans. Several population genetics studies subsequently confirmed the theory. But major questions remained, especially regarding the specific epochs during which the selective pressures exerted by pathogens on human populations were strongest and their impact on the present-day risk of developing inflammatory or autoimmune disorders.
To address these questions, scientists from the Institut Pasteur, Université Paris Cité, the CNRS and the Collège de France, in collaboration with the Imagine Institute and The Rockefeller University (United States), adopted an approach based on paleogenomics. This discipline, which studies the DNA from fossil remains, has led to major discoveries about the history and evolution of humans and human diseases, as illustrated by the decision to award the 2022 Nobel Prize in Physiology or Medicine to the paleogeneticist Svante Pääbo. In the study led by the Institut Pasteur, published on January 13 in the journal Cell Genomics, the scientists analyzed the variability of the genomes of more than 2,800 individuals who lived in Europe over the past ten millennia — a period covering the Neolithic, the Bronze Age, the Iron Age, the Middle Ages and the present.
By reconstituting the evolution over time of hundreds of thousands of genetic mutations, the scientists initially identified mutations that rapidly increased in frequency in Europe, indicating that they were advantageous. These mutations that evolved under “positive” natural selection are mainly located in 89 genes enriched in functions relating to the innate immune response, including especially the OAS genes — which are responsible for antiviral activity — and the gene responsible for the ABO blood group system. Surprisingly, most of these positive selection events, which demonstrate a genetic adaptation to the pathogenic environment, began recently, from the start of the Bronze Age, around 4,500 years ago. The scientists explain this “acceleration” in adaptation by the growth in the human population during this period and/or by strong selective pressures exerted by pathogens in the Bronze Age, probably linked to the spread of severe infectious diseases such as plague.
At the same time, the scientists also looked at the opposite situation, in other words, mutations whose frequency fell significantly over the past ten millennia. These mutations are probably subject to “negative” selection because they increase the risk of disease. They noted that once again, these selection events mainly began in the Bronze Age. Many of these disadvantageous mutations were also located in genes associated with the innate immune response, such as TYK2, LPB, TLR3 and IL23R, and have been confirmed in experimental research to have a deleterious effect in terms of infectious disease risk. The results emphasize the value of adopting an evolutionary approach in research on genetic susceptibility to infectious diseases.
Finally, the scientists explored the theory that the selection exerted by pathogens in the past gave an advantage to alleles conferring resistance to infectious diseases, but that in turn these alleles have increased the present-day risk of autoimmune or inflammatory disorders. They investigated the few thousand mutations known to increase susceptibility firstly to tuberculosis, hepatitis, HIV or COVID-19, and secondly to rheumatoid arthritis, systemic lupus erythematosus or inflammatory bowel disease. By looking at the evolution of these mutations over time, they observed that those associated with an increased risk of inflammatory disorders — including Crohn’s disease — became more frequent over the past 10,000 years, while the frequency of those associated with a risk of developing infectious diseases decreased. “These results suggest that the risk of inflammatory disorders has increased in Europeans since the Neolithic period because of a positive selection of mutations improving resistance to infectious diseases,” explains Lluis Quintana-Murci, director of the study and Head of the Human Evolutionary Genetics Unit (Institut Pasteur/CNRS Evolutionary Genomics, Modeling and Health Unit/Université Paris Cité).
The results of the study, which harnessed the huge potential of paleogenomics, show that natural selection has targeted human immunity genes over the past ten millennia in Europe, especially since the start of the Bronze Age, and contributed to present-day disparities in terms of the risk of infectious and inflammatory diseases.
As well as the institutions mentioned above, this research was supported by the French Foundation for Medical Research (FRM), the Allianz-Institut de France Foundation and the Fondation de France.

Dr. David A. Kessler took over Operation Warp Speed when President Biden entered office, and his departure signals the end of the program.WASHINGTON — Dr. David A. Kessler, who for the past two years has been the behind-the-scenes force driving a vast federal effort to develop and distribute coronavirus vaccines and treatments, said on Friday that he was leaving the Biden administration to return to teaching at the University of California, San Francisco.Dr. Kessler may be best remembered in Washington for a far more public role, as commissioner of the Food and Drug Administration in the 1990s, when he took on the tobacco companies. As chief science officer for the Biden administration’s Covid-19 response, he has operated largely unseen by the public, but his work has affected the lives of millions of Americans.“Six hundred sixty-five million vaccines, 13 million antivirals,” Dr. Kessler said in a brief interview on Friday, referring to the number of doses that Americans have taken since December 2020, shortly before President Biden took office. “We did what we set out to do.”Still, millions of Americans remain unvaccinated. In an interview over the summer, Dr. Kessler talked about the mass vaccination sites he had helped set up, his efforts to distribute the shots to pharmacies and nursing homes and his work to make them available to children.“Our job was getting safe and effective vaccines to be accessible,” he said, “and to make sure that everyone could have it, and that it was easy.”Dr. Kessler’s departure signals the end of Operation Warp Speed, which was started by the Trump administration to develop and distribute coronavirus vaccines. Now the Biden administration is working to shift Covid vaccination from a government-run effort to one that will be handled by the private sector.In his role, Dr. Kessler was responsible for negotiating with drug companies to make certain that vaccines were available to anyone who wanted one — at a price for taxpayers that is far lower than the one companies want to charge on the commercial market.When Mr. Biden was running for office, at the height of the coronavirus pandemic, Dr. Kessler was one half of a two-person team — the other half was Dr. Vivek H. Murthy, now the surgeon general — that briefed the candidate almost daily on matters related to the pandemic. When Mr. Biden became president, Dr. Kessler took over Operation Warp Speed and ran it alongside Gen. Gustave F. Perna, who had worked under President Donald J. Trump.“For decades, Dr. Kessler has worked tirelessly to address our nation’s most challenging public health issues, and his work during the Covid-19 pandemic has been no different,” Xavier Becerra, the secretary of health and human services, said in a statement.

Madagascar is home to a unique biodiversity with a large number of endemic species, among those many lemur species, including the mouse lemurs. This diversity is also found in their retroviruses, a team led by scientists from the Leibniz Institute of Zoo and Wildlife Research (Leibniz-IZW) and the University of Stirling reports in the journal “Virus Evolution.” They analysed the mouse lemur genome and identified viruses of two classes that represent ancient infections of the mouse lemur germline. The viruses now behave similarly to lemur genes and are thus called endogenous retroviruses (ERVs). It was surprising that some of the identified retroviruses are closely related to viruses found in other, very different mammals such as polar bears or domestic sheep. This suggests an intriguing and complex pattern of host switching of retroviruses, much more complex than previously thought.
For their analysis, the team collected blood samples from four species of Malagasy mouse lemurs and screened them using high throughput sequencing. The scientists identified two gamma and three beta retrovirus sequences in the lemurs’ genomes, representing ancient infections of the mouse lemur germlines. Since then, the virus DNA has been incorporated in the host genomes and the viruses are no longer active or infectious. “We were surprised to find that one of the two identified gamma retroviruses was related to an ERV described in polar bears,” states Dr Sharon Kessler, a German Academic Exchange Service (DAAD) supported scientist and Assistant Professor at the University of Stirling. The polar bear virus is young from an evolutionary point of view whereas the lemur virus is old. “How these related viruses infected such geographically separated species is unclear,” Kessler says.
There were further surprises among the beta retroviruses. A virulent retrovirus that infects domestic sheep called Jaagsiekte sheep retrovirus (JSRV), which also forms ERVs in domestic sheep, is thought to be a virus confined to domestic sheep, goats and their relatives — the first cloned sheep “Dolly” had to be euthanised after a JSRV infection and subsequent illness. The mouse lemurs have a closely related JSRV-like virus in their genome. “This suggests that JSRV-like viruses have been more widespread among mammals and are considerably older than previously thought. Why they only show up in such disparate species and in such a punctuated way is curious,” says Prof Alex Greenwood, head of the Leibniz-IZW Department of Wildlife Diseases, where the sample screening was conducted. Similarly, the team also identified a virus in the mouse lemurs related to retroviruses found in squirrel monkeys, vampire bats and marsupials. “This group of viruses is becoming more interesting over time as more and more examples of similar viruses are being found in many places including very young ones that may still have currently infectious exogenous counterparts in nature,” says Greenwood.
Much of the mouse lemur retroviral diversity observed is associated with non-primate viruses, suggesting a complex pattern of viral host switching around the time the ancestors of lemurs colonized Madagascar. Further studies of viral diversity will help to clarify the complex history of retroviral transmission among mammals.
Dr Kessler and Prof Greenwood collaborated with Prof Solofonirina Rasoloharijaona of the University of Mahajanga, (Madagascar), Prof Ute Radespiel of the University of Veterinary Medicine Hannover, Foundation, (Germany) and Dr Kyriakos Tsangaras of the University of Nicosia (Cyprus) in this scientific investigation that was also made possible with funding from the American Association of Physical Anthropologists.
Retroviruses are viruses that replicate by incorporating their genetic material into the genome of a host cell. If the infected cell is a germ cell, the retrovirus can subsequently be passed on as an “endogenous” retrovirus and spread throughout a population as part of the host genome. Repeated infections have resulted in endogenous retroviruses being ubiquitous in mammalian genomes, sometimes making up significant portions of the host genome. However, most retrovirus integrations are very old and already degraded and therefore inactive — their initial impact on host health reduced by millions of years of evolution.