The peak of China's COVID-19 wave is expected to last two to three months, and will soon swell over the vast countryside where medical resources are relatively scarce, a top Chinese epidemiologist has said.
Infections are expected to surge in rural areas as hundreds of millions travel to their home towns for the Lunar New Year holidays, which officially start from Jan. 21, known before the pandemic as the world's largest annual migration of people.
China last month abruptly abandoned the strict anti-virus regime of mass lockdowns that fuelled historic protests across the country in late November, and finally reopened its borders this past Sunday.
The abrupt dismantling of restrictions has unleashed the virus onto China's 1.4 billion people, more than a third of whom live in regions where infections are already past their peak, according to state media.
But the worst of the outbreak was not yet over, warned Zeng Guang, the former chief epidemiologist at the Chinese Center for Disease Control and Prevention, according to a report published in local media outlet Caixin on Thursday.
"Our priority focus has been on the large cities. It is time to focus on rural areas," Zeng was quoted as saying.
He said a large number of people in the countryside, where medical facilities are relatively poor, are being left behind, including the elderly, the sick and the disabled.
The World Health Organization this week also warned of the risks stemming from holiday travelling.
The UN agency said China was heavily under-reporting deaths from COVID, although it is now providing more information on its outbreak.
"Since the outbreak of the epidemic, China has shared relevant information and data with the international community in an open, transparent and responsible manner," foreign ministry official Wu Xi told reporters.
Chinese virologists said on Friday they have discovered one infection with the Omicron subvariant XBB.1.5, which has been described by WHO scientists as the most transmissible sub-variant so far after its rapid spread in the United States in December. There is no evidence yet that it is more severe.
Despite the lack of evidence of the safety of antipsychotics in children, who are smaller in size and still rapidly developing, the number of prescriptions to English youth has doubled between 2000 to 2019, a study suggests.
The researchers from the University of Manchester examined over seven million children and adolescents aged three to 18.
They discovered that youth prescriptions of antipsychotics - drugs used to treat major mental illnesses, such as autism, schizophrenia, and ADHD - increased from 0.06 percent to 0.11 in the past two decades.
While the percentage is small, co-author and senior research fellow at the University of Manchester Matthias Pierce said that the higher prevalence of these disorders, as well as a growing trend to prescribe antipsychotics by clinicians, is concerning.
“However, [it] will help clinicians to evaluate the prescribing of antipsychotics to children more fully and will encourage them to consider better access to alternatives,” Pierce said.
Antipsychotics have been associated with long-term side effects, including sexual dysfunction, infertility, and weight gain leading to diabetes.
For mental illnesses apart from depression and eating disorders, the researchers discovered that risperidone was the most prescribed drug, accounting for over 70 percent of prescriptions.
“We report 20 times more risperidone prescriptions than previously observed,” the authors wrote.
The most prescribed drug for depression was quetiapine, which is approved by the U.S. Food and Drug Administration and associated with the side effects of high blood pressure, vomiting, and fatigue.
The most prescribed medication for eating disorders was olanzapine, with the principal side effect being weight gain, with young males appearing to be at a heightened risk.
A similar study involving a 12-week examination of the use of antipsychotic drugs in children revealed that at the conclusion of the study, all children displayed behavioural change. However, all participants also showed significant adverse effects.
Before agreeing to start their child on antipsychotics to manage aggressive behaviour, parents should ask about alternative treatments, according to Mark Olfson, a research psychiatrist at Columbia University in New York.
He said these might include anger management, counselling for parents on how to address aggression, and other psychosocial options.
The study was published on Jan. 10 in the Lancet Psychiatry.
Shares of UnitedHealth Group Inc. (UNH) climbed 1.3% in premarket trading Friday, after the health insurer reported fourth-quarter profit and revenue that rose expectations and affirmed its 2023 outlook. Net income rose to $$.76 billion, or $5.03 a share, from $4.07 billion, or $4.26 a share, in the year-ago period. Excluding nonrecurring items, adjusted earnings per share increased to $5.34 from $.48, to beat the FactSet consensus of $5.17. Revenue grew 12.3% to $82.79 billion, above the FactSet consensus of $82.48 billion, while revenue from premiums increased 12.4% to $64.70 billion, just above expectations of $64.67 billion. The company affirmed its guidance ranges provided in late-November for 2023 adjusted EPS of $24.40 to $24.90, which compares with the FactSet consensus of $24.94, and revenue of $357 billion to $360 billion, which surrounds expectations of $356.8 billion. The stock has lost 2.8% over the past three months through Thursday, while the SPDR Health Care Select Sector ETF has rallied 8.1% and the Dow Jones Industrial Average has climbed 13.8%.
A group of 43 national security professionals published an open letter on Jan. 11 criticizing news organizations and scientific publications that dismissed the possibility that the COVID-19 pandemic might have been the result of a lab leak.
The letter is addressed “To the editors, authors, and contributors to major scientific, medical, and journalistic publications worldwide.” The addressees include The Lancet, Nature Medicine, The New York Times, and TIME magazine.
The letter was coordinated by the Vandenberg Coalition, and included signatures from House Foreign Affairs Committee Chairman Michael McCaul (R-Texas), former U.S. National Security Advisor Robert O’Brien, Former U.S. Deputy National Security Advisor Matthew Pottinger, and analysts from the Heritage Foundation, the Hudson Institute, the Center for Strategic and International Studies (CSIS), and other security and foreign policy analysts.
“Leading scientific journals censored dissenting voices; many science writers at major news outlets promoted narratives or asserted conclusions unsubstantiated by evidence; reporters failed to make even cursory attempts at surfacing potential conflicts of interest of their sources,” the letter states.
“This served to hamper national and international policy discussions about how to mitigate against future pandemics of any origin—natural, accidental, or deliberate.”
The letter faults editors and reporters at news organizations and scientific publications for stifling debate on the origins of the virus.
The letter references a Fox News article about a May 2021 tweet by a New York Times reporter who said, “Someday we will stop talking about the lab leak theory and maybe even admit its racist roots. But alas, that day is not yet here.”
The New York Times reporter deleted the tweet the same day she wrote it.
“Our security and prosperity depend on rigorous scientific debate, research, and scholarship, as well as an intrepid and independent news media,” the letter continues.
“The responsibility of scientists and journalists alike is to ask hard questions and seek truth. By prematurely dismissing or stigmatizing certain questions—from the very outset of the pandemic—many prominent scientists and journalists failed in their duty.”
The letter went on to list “notable failures” by the various news and scientific publications. A February 2020 statement by The Lancet “asserted without evidence that questioning the supposed natural origin of COVID-19 constituted ‘misinformation’ and a ‘conspiracy theory,” the letter states.
Peter Daszak, president of EcoHealth Alliance, was listed as a co-author the February 2020 statement by The Lancet. EcoHealth Alliance worked directly with China’s Wuhan laboratories to research coronaviruses. The Lancet subsequently acknowledged questions if Daszak had a “competing interest” when he co-authored the 2020 statement.
The letter authors also noted that a report by Nature Medicine, which “became one of the most-cited academic journal articles in history” had “effectively stigmatized anyone who questioned whether the outbreak may have originated in a laboratory.”
Researchers are reporting progress on a blood test that can detect multiple cancers in a relatively simpler, and potentially less pricey way than other tests under development.
The test picks up certain cancer signals in the blood using a fairly straightforward method: counting bits of DNA that appear to be "broken" in unexpected places.
In the new study, scientists found that the approach can distinguish people with any of 11 different types of cancer from people who are cancer-free. Not only that, it can do so using a relatively small blood sample, according to senior researcher Dr. Muhammed Murtaza, of the University of Wisconsin's School of Medicine and Public Health, in Madison.
That's relative to other blood tests under development for cancer screening, which typically require multiple tubes of blood.
"The biggest advantage of our approach would probably be in cost-effectiveness," Murtaza said, although he added that it's hard to make predictions on real-world costs.
The study, published Jan. 11 in the journal Science Translational Medicine, is among the latest in the broader push to develop blood tests that can serve as a one-stop screening for multiple cancers.
A number of companies are working on such "multi-cancer" early detection tests. Essentially, they are all based on the fact that tumors shed bits of genetic material in the blood. If a test can detect those tumor signals, that could provide a simple, noninvasive way to screen for various cancers—including ones that now lack any screening method.
Where the tests vary is in what, exactly, they are measuring, Murtaza explained.
He and his colleagues took the approach of analyzing DNA "fragmentation patterns." Both tumor cells and healthy cells regularly release pieces of DNA into the blood. But because tumors express different genes than normal body cells do, they also differ in how those DNA bits break off.
The new test looks at the "end position" of DNA fragments in the blood, to see if the breaks happened in "unexpected places," Murtaza said.
He described it as a "simple method" that allows for a smaller blood sample containing a limited supply of DNA (which, in the world of DNA, amounts to a minimum of 1 million fragments).
For the study, the researchers analyzed blood samples from 286 healthy people, 103 who had non-cancer medical conditions, and 994 people with one of 11 types of cancer. They ranged from breast and ovarian cancers to melanoma, to rarer cancers like bile duct tumors and the deadly brain cancer glioblastoma.
Overall, the researchers found, the test did a good job of pinpointing which blood samples came from cancer patients, including those who had early-stage cancer, which is important in a screening test.
The test had an "area-under-curve" (AUC) of 0.91 for cancer overall, and 0.87 for stage 1 cancer, according to the researchers. The AUC is a measure of test accuracy that ranges from 0 to 1: the closer it is to 1, the better.
More research is still needed, according to Murtaza. One of the next steps, he said, is to see how well the test performs in detecting a single cancer, rather than multiple ones—including pancreatic cancer, a deadly disease for which there is no screening test.
A researcher who was not involved in the study agreed that the approach "potentially has some advantages" over other blood tests under development.
"It's another approach that may be a little simpler, and maybe less expensive," said Dr. David Polsky, of NYU Langone's Perlmutter Cancer Center, in New York City.
Like Murtaza, he said the test is "not ready for prime time," and more research is needed.
With any test aimed at screening healthy people for cancer, Polsky said, there are important measures of its performance: its sensitivity, which refers to the test's ability to correctly identify people who have cancer; and its specificity, or its ability to correctly identify people who do not have cancer.
Specificity is critical, Polsky noted, because if it's too low, the test will generate a lot of false-positive results that lead to unnecessary follow-up testing—and anxiety.
Some other blood tests for cancer screening are further along in development, including one called Galleri that screens for over 50 cancers with a single blood draw. It's currently being put to the test in the Pathfinder 2 study, being run at multiple U.S. medical centers.
There are currently no multi-cancer early detection tests approved by the U.S. Food and Drug Administration.
More information: Karan K. Budhraja et al, Genome-wide analysis of aberrant position and sequence of plasma DNA fragment ends in patients with cancer, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.abm6863
The American Cancer Society has more on blood tests under study for cancer screening.
Fungi such as Aspergillus are so common in our surroundings that we breathe in hundreds to thousands of spores every day. In healthy people, fungi typically pose no threat, but they can cause deadly infections in those with compromised immune systems. However, it is increasingly recognized that viral infections such as influenza or SARS-CoV-2 can increase the risk of invasive Aspergillus infections even in healthy people.
The World Health Organization (WHO) has stated that invasive fungal infections are an increasing threat to human health and has reiterated that more research is needed. Until now little was known about how the Aspergillus fungus was able to take root, and what could be done to get rid of it. Researchers at the University of Calgary working with researchers at McGill University have provided new insight on why the immune system fails.
"We discovered that influenza and COVID-19 destroy a previously unknown natural immunity that we need to resist invasive fungal infections," says Nicole Sarden, a Ph.D. candidate at the University of Calgary and first author on the study.
The findings published in Science Translational Medicine show that two types of white blood cell (neutrophils and a unique type of B cells) normally work together to fight fungal infection. However, viruses like SARS-CoV-2 and influenza impede the special B cells from doing their job.
Working with mice and human blood and tissue samples, the researchers were able to see that following a viral infection, neutrophils sensed a fungal infection and were gathering nearby, but weren't acting to destroy the invader as expected. The scientists delved further and learned that viral molecules were rendering these B cells apathetic, preventing them from cooperating with neutrophils as they normally would, and thus protecting the fungi from destruction. Understanding this process led to the next discovery.
"We also found that current therapies exist that could be repurposed in a realistic and meaningful way to replace the natural antibodies not being produced by the virally-damaged B cells and re-establish the neutrophils ability to fight these infections," says Sarden.
"This research was sparked by a young man I cared for in the ICU on life support who died of influenza-associated aspergillosis, where every therapy we tried failed," says Dr. Bryan Yipp, MD, clinician researcher at the Cumming School of Medicine and senior author on the study. "Our findings are very timely given the high numbers of patients affected by multiple respiratory viruses including influenza."
Sarden and Yipp believe these findings will lay the groundwork for new diagnostic tests, based on natural antibody levels to predict who is at the highest risk for invasive fungal infections, and that currently available antibody replacement strategies could be tested to treat Aspergillus infections in future clinical trials.
"These discoveries provide a new understanding of how we can best support the body to fight off deadly fungal infections," says Yipp.
More information: Nicole Sarden et al, A B1a–natural IgG–neutrophil axis is impaired in viral- and steroid-associated aspergillosis, Science Translational Medicine (2022). DOI: 10.1126/scitranslmed.abq6682
An international study 13 years in the making demonstrates for the first time that degradation in the way DNA is organized and regulated—known as epigenetics—can drive aging in an organism, independently of changes to the genetic code itself.
The work shows that a breakdown in epigenetic information causes mice to age and that restoring the integrity of the epigenome reverses those signs of aging.
Findings are published online Jan. 12 in Cell.
"We believe ours is the first study to show epigenetic change as a primary driver of aging in mammals," said the paper's senior author, David Sinclair, professor of genetics in the Blavatnik Institute at Harvard Medical School and co-director of the Paul F. Glenn Center for Biology of Aging Research.
The team's extensive series of experiments provide long-awaited confirmation that DNA changes are not the only—or even the main—cause of aging. Rather, the findings show, chemical and structural changes to chromatin—the complex of DNA and proteins that forms chromosomes—fuel aging without altering the genetic code itself.
"We expect the findings will transform the way we view the process of aging and the way we approach the treatment of diseases associated with aging," said co-first author Jae-Hyun Yang, research fellow in genetics in the Sinclair lab.
The authors say that because it's easier to manipulate the molecules that control epigenetic processes than to reverse DNA mutations, the work points to new avenues that focus on epigenetics rather than genetics to prevent or treat age-related damage.
First, the results need to be replicated in larger mammals and in humans. Studies in nonhuman primates are currently underway.
"We hope these results are seen as a turning point in our ability to control aging," said Sinclair. "This is the first study showing that we can have precise control of the biological age of a complex animal; that we can drive it forwards and backwards at will."
Beyond mutations
Perhaps the most burning question for those who study aging is what causes it.
For decades, a reigning theory in the field was that aging arises from an accumulation of changes to DNA, primarily genetic mutations, which over time prevent more and more genes from functioning properly. These malfunctions, in turn, cause cells to lose their identity, so that tissues and organs break down, leading to disease and ultimately death.
In recent years, however, studies have increasingly hinted that there's more to the story.
For instance, some researchers found that some people and mice with high mutation rates don't show signs of premature aging. Others observed that many types of aged cells have few or no mutations.
Researchers started wondering what else works with or instead of DNA changes to cause aging. A list of possible culprits grew. Among them were epigenetic changes.
A component of epigenetics is the physical structures such as histones that bundle DNA into tightly compacted chromatin and unspool portions of that DNA when needed. Genes are inaccessible when they're bundled up but available to be copied and used to produce proteins when they're unspooled. Thus, epigenetic factors regulate which genes are active or inactive in any given cell at any given time.
By acting as a toggle for gene activity, these epigenetic molecules help define cell type and function. Since each cell in an organism has basically the same DNA, it's the on-off switching of particular genes that differentiates a nerve cell from a muscle cell from a lung cell.
"Epigenetics is like a cell's operating system, telling it how to use the same genetic material differently," said Yang, who is co-first author with Motoshi Hayano, a former postdoctoral fellow in the Sinclair lab who is now at Keio University School of Medicine in Tokyo.
In the late 1990s and early 2000s, Sinclair's lab and others showed in yeast and mammals that epigenetic changes accompany aging. Yet they couldn't tell whether these changes drove aging or were a consequence of it.
It wasn't until the current study that Sinclair's team was able to disentangle epigenetic from genetic changes and confirm that a breakdown in epigenetic information does, in fact, contribute to aging in mice.
ICE mice
The team's main experiment involved creating temporary, fast-healing cuts in the DNA of lab mice.
These breaks mimicked the low-grade, ongoing breaks in chromosomes that mammalian cells experience every day in response to things like breathing, exposure to sunlight and cosmic rays, and contact with certain chemicals.
In the study, to test whether aging results from this process, the researchers sped the number of breaks to simulate life on fast-forward.
The team also ensured that most of the breaks were not made within the coding regions of the mice's DNA—the segments that make up genes. This prevented the animals' genes from developing mutations. Instead, the breaks altered the way DNA is folded.
Sinclair and colleagues called their system ICE, short for inducible changes to the epigenome.
At first, epigenetic factors paused their normal job of regulating genes and moved to the DNA breaks to coordinate repairs. Afterward, the factors returned to their original locations.
But as time passed, things changed. The researchers noticed that these factors got "distracted" and did not return home after repairing breaks. The epigenome grew disorganized and began to lose its original information. Chromatin got condensed and unspooled in the wrong patterns, a hallmark of epigenetic malfunction.
As the mice lost their youthful epigenetic function, they began to look and act old. The researchers saw a rise in biomarkers that indicate aging. Cells lost their identities as, for example, muscle or skin cells. Tissue function faltered. Organs failed.
The team used a recent tool developed by Sinclair's lab to measure how old the mice were, not chronologically, in days or months, but "biologically," based on how many sites across the genome lost the methyl groups normally attached to them. Compared to untreated mice born at the same time, the ICE mice had aged significantly more.
Young again
Next, the researchers gave the mice a gene therapy that reversed the epigenetic changes they'd caused.
"It's like rebooting a malfunctioning computer," said Sinclair.
The therapy delivered a trio of genes—Oct4, Sox2, and Klf4, together named OSK—that are active in stem cells and can help rewind mature cells to an earlier state. (Sinclair's lab used this cocktail to restore sight in blind mice in 2020.)
The ICE mice's organs and tissues resumed a youthful state.
The therapy "set in motion an epigenetic program that led cells to restore the epigenetic information they had when they were young," said Sinclair. "It's a permanent reset."
How exactly OSK treatment achieved that remains unclear.
At this stage, Sinclair says the discovery supports the hypothesis that mammalian cells maintain a kind of backup copy of epigenetic software, that when accessed, can allow an aged, epigenetically scrambled cell to reboot into a youthful, healthy state.
For now, the extensive experiments led the team to conclude that "by manipulating the epigenome, aging can be driven forwards and backwards," said Yang.
From here
The ICE method offers researchers a new way to explore the role of epigenetics in aging and other biological processes.
Because signs of aging developed in the ICE mice after only six months rather than toward the end of the average mouse life span of two and a half years, the approach also saves time and money for researchers studying aging.
Researchers can also look beyond OSK gene therapy in exploring how lost epigenetic information might be restored in aged organisms.
"There are other ways to manipulate the epigenome, like drugs and small molecule chemicals that induce gentle stress," said Yang. "This work opens a door for applying those other methods to rejuvenate cells and tissues."
Sinclair hopes the work inspires other scientists to study how to control aging to prevent and eliminate age-related diseases and conditions in humans, such as cardiovascular disease, type 2 diabetes, neurodegeneration, and frailty.
"These are all manifestations of aging that we've been trying to treat with medicines when they arise, which is almost too late," he said.
The goal would be to address the root causes of aging to extend human health span: the number of years that a person remains not just alive but well.
Medical applications are a long way off and will take extensive experiments in multiple cell and animal models. But, Sinclair said, scientists should think big and keep trying in order to achieve such dreams.
"We're talking about taking someone who's old or sick and making their whole body or a specific organ young again, so the disease goes away," he said. "It's a big idea. It's not how we typically do medicine."
More information: Jae-Hyun Yang et al, Loss of epigenetic information as a cause of mammalian aging, Cell (2023). DOI: 10.1016/j.cell.2022.12.027
