The first person to publicly release the genome sequence of the virus that causes COVID-19 — virologist Zhang Yongzhen — appears to have resolved a public dispute with the Shanghai Public Health Clinical Center (SPHCC), Fudan University, that erupted last week.
Zhang had been photographed camping outside his laboratory since Sunday, after the SPHCC closed the lab.
The SPHCC did not respond to Nature’s request to comment but has released public statements saying the laboratory was one of several that needed renovations — and that it provided Zhang’s team with an alternative space.
According to social media posts on Zhang’s personal Weibo account, the institute gave the research team two days to leave but the SPHCC did not initially specify where they should relocate. Later, Zhang said officials told his team to move to a lab that did not have the necessary biosafety conditions to store their samples, which contain unknown pathogens. Zhang’s lab is a biosafety level 3 laboratory.
Zhang said he had been sleeping outside his laboratory since Sunday night, even in the rain. The social media posts include photos of him lying under blankets.
Zhang told Nature on Monday that his situation was “terrible”.
“You don’t know what I have experienced,” he said, but declined to comment further.
According to the social media account of Chen Yanmei, a virologist at the SPHCC, and a member of Zhang’s team, their students’ incomplete experiments were now “impossible to save”. Chen said she was also camping out, inside the lab. Chen also declined to be interviewed by Nature.
But by late Tuesday night, Zhang said in a post that a tentative agreement had been reached with the SPHCC to resume normal research activity in the laboratory. The post states that Zhang will work with the centre to relocate the laboratory and restart research.
Virus sequence
In 2020, Zhang was the first scientist — together with Edward Holmes, a virologist at the University of Sydney in Australia — to share the genome of SARS-CoV-2 with the world on the website virological.org. That act is widely credited as a key factor enabling the swift development of vaccines against COVID-19.
Since 2020, Zhang has received international acclaim. That year, Zhang featured in Nature’s 10 — an annual list of people behind key developments in science, and in 2022 he was awarded the Mohammad bin Rashid Al Maktoum Knowledge Award, which carries a US$1 million bursary.
Nature’s 10: ten people who helped shape science in 2020
But Holmes, a long-time collaborator of Zhang’s, says that since 2020, Zhang’s research output has dwindled. Before 2020, Zhang had an extensive research network and would collect samples of animals and people to study viral evolution, says Holmes. But since 2020, Zhang’s work has largely involved analysing previously collected samples and Holmes’s own collaboration with Zhang is less prolific. “He drove that collaboration but there is nothing to collaborate on now; he hasn’t been able to get any data,” says Holmes. “All I can do is offer support from afar.”
According to the Dimensions database, Zhang co-authored 5 research articles in 2018, 9 in 2019 and 18 in 2020. But that growing publication rate dropped to 3 in 2021 and 4 in 2022. Zhang co-authored 6 articles in 2023, none of which contained original data.
Holmes believes the lab closure is part of an effort to sideline Zhang for unauthorized sharing of data. “It is heartbreaking to watch,” he says. “It is unfathomable to me to have a scientist of that calibre sleeping outside his lab.”
International star
But Yanzhong Huang, a specialist in Chinese health policy at the Council on Foreign Relations in New York City, says the true nature of the dispute and protest are “shrouded in mystery”.
Fan Xiaohong, a physician who heads the SPHCC told reporters for Chinese newspaper Southern Weekly that Zhang’s contract had expired, but he had refused to leave. A post on Zhang’s social media said that although his own contract with SPHCC had formally ended in 2023, members of his team had renewed their contracts with the hospital, and the laboratory is still owed funding.
Even without clarity on the details of the dispute, Dali Yang, a researcher who studies politics in China at the University of Chicago, says it’s concerning that Zhang is sleeping outside his lab. “Many people who know about him are aghast because he is truly an international star,” says Yang.
In late 2020, COVID-19’s global death toll was rising as cold weather in the Northern Hemisphere and holiday gatherings spurred rapid transmission of SARS-CoV-2 in the absence of a vaccine. Scientists and public-health officials were desperate for new ways to track the virus, which often moved faster than contact tracers could follow it.
Tong Zhang, an environmental engineer and microbiologist at the University of Hong Kong (HKU), and his colleagues were pioneers of what was fast becoming a popular surveillance method. They had been collecting periodic wastewater samples from about two dozen maintenance holes in the city and testing the sewage for coronavirus DNA, with support from Hong Kong’s government. In late December, they traced an outbreak to a single apartment building where there had been no sign of cases1.
The government quickly took action. Officials tested all of the building’s 2,000-odd residents; 9 tested positive. “Those people were isolated and went to a quarantine site. So they stopped the transmission chain,” Zhang says. After that success, he and his colleagues expanded their efforts.
These scientists traced a new coronavirus lineage to one office — through sewage
Wastewater testing remains part of Hong Kong’s COVID-19 strategy to this day. Zhang’s team tests for the coronavirus at about 20 sites across the city each week, he says, and the team has expanded the analysis of these samples to cover other pathogens, including influenza, rotavirus, norovirus and mpox, as well as markers of antimicrobial resistance. He views wastewater testing as a way to gauge the health of an entire community at once. “If we can make the methodology more standardized”, this tool becomes a “promising and exciting” way to screen the world for pathogens, including those that scientists haven’t yet identified,he says.
Many researchers are following similar approaches. There are currently more than 4,600 sites around the world where wastewater is being collected for SARS-CoV-2 testing, and some of the research teams involved are investigating other potential applications, such as tracking illicit drug use and even the prevalence of cancer.
But whether this has the potential to be an effective public-health strategy is still a matter of debate. Leo Poon, a colleague of Zhang’s at HKU’s School of Public Health, says that more research should be done before health agencies expand their sewage testing programmes and make this surveillance part of their routine budgets. “There’s still a lot unknown,” he says, particularly in terms of testing for pathogens besides SARS-CoV-2. “I think there’s a steep learning curve at the moment: when we detect something, what does it mean?”
By the end of 2020, several studies had shown that levels of coronavirus in public water systems could correlate with the number of COVID-19 cases in the community. For example, researchers at Stanford University in California found that viral levels in wastewater rose and fell with cases in the San Francisco Bay area3. The group that led the work has gone on to found the WastewaterSCAN project, which tests samples from nearly 200 sites across the United States (see ‘Peak transmission’).
Source: WastewaterSCAN
In the most successful wastewater projects, scientists say, researchers collaborated directly with public-health officials, who used the data to inform COVID-19 safety policies. This happened in rural parts of Ghana, where, as in Hong Kong, wastewater testing found COVID-19 cases that hadn’t been caught by other types of surveillance. Habib Yakubu, a public-health researcher at Emory University’s Center for Global Safe Water, Sanitation, and Hygiene in Atlanta, Georgia, worked with a team of Ghanaian scientists to develop testing methods that accounted for the country’s limited public sewers and laboratory equipment. They tried this in two rural districts, Nanumba North and Mion, where government officials suspected that COVID-19 might be spreading but where clinical testing hadn’t identified any cases.
The researchers worked with community leaders to identify sites for sampling, including schools, health-care facilities, markets and streams used for washing clothes. “We looked at, where do people converge?” Yakubu says. COVID-19 was, in fact, present in these regions, the researchers found. As a result, officials increased public-health activities, including community education and vaccination efforts. The team tested for other diseases that are common in Ghana, including cholera and typhoid, which has also informed health actions.
For scientists at the Tata Institute for Genetics and Society in Bengaluru, India, the need for wastewater testing for COVID-19 became clear after the country’s devastating wave of the Delta variant of SARS-CoV-2 in early 2021, says Farah Ishtiaq, an evolutionary ecologist at Tata who leads the COVID-19 surveillance programme in the city. She and her colleagues worked with officials to set up testing at 28 water treatment plants in Bengaluru — a logistically challenging task, because the team had to collect samples manually rather than using the automated samplers common in higher-income nations.
This testing proved its worth during the spread of the Omicron variant in Bengaluru the following year, Ishtiaq says. Wastewater data demonstrated that Omicron variants were spreading widely across the city at a time when data from the health-care system were limited. Officials responded by renewing mask mandates and placing restrictions on large gatherings, she says.
Inspired by case studies such as these, the field has grown drastically over the past 4 years, with hundreds of research teams now testing in 72 countries, according to the COVIDPoops19 dashboard maintained by environmental engineer Colleen Naughton and her colleagues at the University of California, Merced (see ‘Uneven coverage’).
In December 2023 and January 2024, it was clear that COVID-19 was spreading widely in several parts of the world. But public-health agencies had severely cut back on conventional testing and surveillance programmes, leading to uncertainty about how much the coronavirus was spreading, and a sudden focus on wastewater-based epidemiology.
Some scientists and social-media commentators stated that SARS-CoV-2 levels in wastewater correlated with specific case numbers, estimating huge surges in the United States and Europe. But others cautioned that wastewater surveillance is not reliable enough to predict true infection numbers. There’s a “false sense of precision” in such estimates, says Sam Scarpino, an epidemiologist at Northeastern University in Boston, Massachusetts, who has worked on COVID-19 data systems.
Estimates are difficult to make because the sewage data differ considerably from conventional health indicators. In typical surveillance, data represent individual infected people who can be identified through contact tracing, isolated and treated. In wastewater surveillance operations, data can represent entire communities.
COVID variants found in sewage weeks before showing up in tests
They make “a litre represent a million people”, says Douglas Manuel, a public-health physician at the University of Ottawa in Canada. Manuel and his colleagues have identified several variables that can alter results from such screenings; these include population density, precipitation, sample composition, handling and testing methods and quality-control measures4. For example, as snow melts in Ottawa’s spring, it flows into the wastewater system and “scours out” solid waste that might have built up in the pipes, Manuel says. This could interfere with findings relating to SARS-CoV-2 measurements.
To account for those variables, researchers tend to compare measurements from one site over time. The US Centers for Disease Control and Prevention (CDC), for instance, developed a metric called the wastewater viral activity level that compares a testing site’s recent SARS-CoV-2 measurement to past ones, then averages those comparison values across larger regions.
These comparison metrics can be helpful for presenting wastewater results to the public, but they gloss over the data’s complexity. Bilge Kocamemi, an environmental engineer at Marmara University in Istanbul and a project coordinator for Turkey’s wastewater testing, says that she quickly realized that “scientific representation of the data makes the data unusable for the public”. Instead, she and her colleagues developed a relatively simple COVID-19 map: testing sites are displayed in different shades of yellow and green, depending on how high SARS-CoV-2 levels are. This coloured scale is not precise, Kocamemi says, but it’s easy for people who don’t have a scientific background to understand.
Improving estimates
Modelling case counts — or other metrics of COVID-19 spread in a community, such as how many people will be hospitalized — from viral levels in wastewater is difficult, but not impossible, say scientists who work on this challenge. Such models would make it easier for health officials to make policy decisions on the basis of sewage data.
The myriad ways sewage surveillance is helping fight COVID around the world
The CDC’s Center for Forecasting and Outbreak Analytics in Washington DC, which launched in 2022, is one group taking on this challenge. Wastewater data are “a really good leading indicator” for COVID-19’s burden on hospitals, says Dylan George, the centre’s director. In February, George and his colleagues released new hospital forecasting models informed by wastewater data, among other metrics (see go.nature.com/43xumbz). Studies have shown that such models are more accurate when they use wastewater data in tandem with data from the health-care system, rather than just one of those sources5.
George cautions that ongoing research will be needed to better understand the connection between virus levels in wastewater and disease levels in a community. For example, some scientists think that virus levels might change as SARS-CoV-2 continues to mutate; a variant known as JN.1 might cause people to shed more virus particles, or shed them for longer compared with previous variants, George says. “I think that’s going to be an active area of research going forward.”
Modellers would like to have more detailed clinical testing data to allow them to make better comparisons between wastewater results and community infections. The challenge is often even greater for researchers testing wastewater for other viruses, says Casandra Philipson, a scientist at Ginkgo Bioworks, a company in Boston that analyses sewage from aeroplanes and airports, along with conducting research into new biosecurity tools. Philipson says that there are decent clinical data available for COVID-19, flu and respiratory syncytial virus. But, she adds, “When you get outside of those three pathogens, there really is a massive data scarcity issue.”
What else can be tested in sewage?
Some scientists are interested in a range of other diseases and health indicators that show up in people’s waste.
Manual wastewater sampling in India.Credit: Environmental Images/Universal Images Group/Shutterstock
Bernd Manfred Gawlik, who coordinates wastewater work at the European Commission’s Joint Research Centre in Brussels, calls wastewater the “dirty blood of the city”, and compares sewage sampling to blood testing. “We are now only starting to understand” how to diagnose this “blood” at the collective level, he says.
One common target of testing is antimicrobial resistance (AMR), an area of wastewater research that pre-dates the pandemic. Ishtiaq, in Bengaluru, says that “AMR is a huge problem in this part of the world”, because many people use unregulated antibiotics. Her research has expanded from COVID-19 testing to a multifaceted, genomic platform that can look for both viral and bacterial infections. Wastewater data will help researchers to understand which pathogens are driving infections and communicate that information to physicians, she says.
Fatma Guerfali, a molecular biologist and bioinformatician at the Pasteur Institute in Tunis, is also tracking AMR in Tunisia, one of the countries considered most at risk. Guerfali says that she and her colleagues are working with the country’s health agency, as well as with research collaborators in other African countries, to determine how best to expand the programme, which started with COVID-19 testing.
How sewage could reveal true scale of coronavirus outbreak
Beyond global targets such as AMR and flu, wastewater testing priorities differ according to local health challenges. Because this testing can pick up a wide variety of pathogens, scientists often consult with health agencies to determine which targets to prioritize. In Louisville, Kentucky, for example, Ted Smith, director of the Center for Healthy Air, Water and Soil at the University of Louisville, and his colleagues are testing for a ‘panvirome panel’ that includes about 30 pathogens of interest to the local health agency. Last year, the testing picked up measles during an outbreak in the state, and health officials used the data to inform vaccination programmes, alerts for physicians and other health efforts, he says.
Another area of expansion lies in testing chemicals that people excrete into wastewater. Some researchers, such as those at the start-up company Biobot Analytics in Cambridge, Massachusetts, are screening for opioids and other drugs with a risk of misuse. Smith and his colleagues are testing sewage for compounds indicative of exposure to air pollution and they have started research into lead levels. “Every day, we come up with new things that we can interrogate wastewater for,” he says.
A few researchers are even going beyond diseases spread by humans to those spread by animals. In 2022, scientists published work linking new SARS-CoV-2 variants in New York City’s wastewater to the city’s rats6. Ishtiaq is looking at avian flu in Bengaluru, and Ekta Patel, a scientist at the International Livestock Research Institute in Kenya, is studying animal diseases there.
Patel and her colleagues are sampling sewage at slaughterhouses and testing for 66 pathogens, including anthrax, brucellosis, and Rift Valley fever. To complement the wastewater tests, Patel hopes her team can collect data from veterinary clinics and community hospitals.
Some wastewater scientists reflect on how different the early days of the COVID-19 pandemic might have been had there been a robust global sewage-surveillance system in place. Researchers could have “immediately retroactively screened wastewater all around the planet” as soon as the virus’s sequence was released, Scarpino says. This screening could have led to a global list of places SARS-CoV-2 was already spreading, informing strategies to contain the virus even before clinical testing was widely available.
Scarpino argues that such a system would require major financial investment, national and scientific leaders who can take ownership of those projects and standards that make wastewater data more comparable across countries7.
The current COVID-19-testing community “came out of need and chaos”, says Megan Diamond, who works on wastewater surveillance at the Rockefeller Foundation in New York City. Global and regional institutions such as the World Health Organization, the European Union and the Africa Centres for Disease Control and Prevention might need to step up and offer guidance for testing, data sharing and standards, Diamond says.
Gawlik has worked on one such broad effort: the Global Consortium for Wastewater and Environmental Surveillance for Public Health, or GLOWACON, which was launched in Brussels in March. By recruiting more than 300 collaborators from around the world, including scientists, government officials and representatives of international organizations, to this consortium, he hopes to advance new methods for diagnosing health issues from the “dirty blood” of cities around the world.
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A typical mouse embryo (left) has four limbs. An embryo in which a particular gene was switched off halfway through development has six limbs, and several of its internal organs protrude from its abdomen.Credit: Anastasiia Lozovska et al/Nat. Comms
Developmental biologist Moisés Mallo and his colleagues inactivated a gene in a mouse embryo to see how the change affected spinal-cord development. One of the bioengineered embryos developed genitals that looked similar to two extra hind limbs. The finding led the researchers to unexpected discoveries about which changes in DNA’s 3D structure affect how embryos develop. “I didn’t choose the project, the project chose me,” Mallo says.
South Korea will become the first East Asian country to join the European Union’s €95-billion (US$102-billion) Horizon Europe research-funding programme. The country’s researchers will be eligible to apply for grants from a €53.5 billion pot of funding for research into global challenges in health, energy, climate change and industrial competitiveness. Last year, New Zealand became the first country to ‘associate to’ Horizon Europe, Canada will be signing on later this year, and Singapore and Japan are in preliminary discussions with the European Commission.
Studies in mice reveal that when long-term memories are formed, the DNA in some nerve cells snaps, triggering an immune response responsible for repair. This DNA damage-and-repair cycle might be a way for nerve cells to make memories that last. When mice were trained to remember an electrical shock, the nerve cells initiated an inflammatory response mediated by the TLR9 protein. When the researchers deleted the gene encoding the TLR9 protein from mice, the animals had trouble recalling long-term memories: they forgot the place where they had previously been shocked. These findings contribute to the picture that forming memories is a “risky business”, says neurobiologist Li-Huei Tsai.
Before the collapse of cryptocurrency exchange FTX and the jailing of its chief exec Sam Bankman-Fried, the company allocated tens of millions of dollars to effective altruism — a philanthropic movement dedicated to tackling long-term risks to humanity, such as climate change. This included giving money to research organizations and scientists, many of whom are under pressure to return the money. Some people are concerned that news of the fraud has damaged the perception of effective altruism itself. “We were really gearing up to this big change,” says Sawyer Bernath of the Berkeley Existential Risk Initiative. “All of a sudden it turned out to be all fake.”
Efforts such as the Patient-Led Research Collaborative have played a crucial role in advising, designing and even funding basic and clinical research into long COVID. Its influential survey has amassed more than 1,000 citations. Co-founder Lisa McCorkell is among the patient advocates who say that despite the fact that such efforts can worsen their symptoms, they have little choice but to get involved. “We’re driven by desperation, out of improving our own quality of life.”
A spreadsheet that has been shared between graduate students around the world for more than a decade helps academics in management navigate the job market. Refreshed each year, the spreadsheet’s tabs act as a job-listings board — and a forum for questions and frustrations. “If that sounds similar to Slack and other messaging tools, it is,” writes business researcher Silvia Sanasi. “But the spreadsheet is completely anonymous. It is also incredibly flexible, quick to load and easy to search. Plus, researchers are already well versed in spreadsheets — and appreciate the ability to trawl job-search boards while looking as if they’re working.”
Palaeobotanist Estella Bergere Leopold’s investigations of fossil pollen and spores provided some of the first insights into the evolution of modern plant communities. In 1955, Leopold became one of the few female scientists at the US Geological Survey, where her studies revealed the existence of a tropical rainforest in the south Pacific millions of years ago. Leopold was also an ardent conservationist and activist who traced back her unbridled enthusiasm for ecology to her childhood spent on a farm in Wisconsin. “Without loving nature,” she said in 2011, “who’s going to want to protect it?” Leopold has died, aged 97.
A bird-like brain might have been the ancestral crucible for dreams, writes cultural curator Maria Popova. In ostriches, which belong to the most ancient group of birds, and platypuses, which are part of the most ancient mammal group, dream-like activity was found in the brainstem. In other birds and mammals, dream-rich sleep takes place primarily in the forebrain, suggesting that dreaming slowly migrated into this evolutionarily younger structure. “The most haunting intimation of the research on avian sleep is that without the dreams of birds, we too might be dreamless,” Popova says.
Credit: CTIO/NOIRLab/DOE/NSF/AURA; Image processing: T. A. Rector, Univ. Alaska Anchorage/NSF’s NOIRLab; M. Zamani & D. de Martin, NSF’s NOIRLab
This stunning photo shows the Vela supernova remnant, an expanding nebula of cosmic debris created by a massive stellar explosion around 11,000 years ago. The image was created by separately capturing light of distinct wavelengths using filters and then combining them.
When Lisa McCorkell got COVID-19 in March 2020, her symptoms were mild. Her physicians told her to isolate from others and that she would recover in a few weeks. But the weeks stretched into months and McCorkell, who was working on a master’s degree in public policy at the University of California, Berkeley, started having debilitating and bewildering symptoms: fatigue, dizziness and shortness of breath. Previously an avid runner, McCorkell found her heart racing from simple efforts.
She struggled to find an explanation, and soon realized that her physicians didn’t know any more about her condition than she did. To complicate matters, the limited availability of high-quality testing for the coronavirus SARS-CoV-2 in the early days of the pandemic left many of her doctors wondering whether her symptoms were really due to COVID-19 at all. “I didn’t have health-care providers that took me seriously,” McCorkell says. “That largely pushed me out of the health-care system.”
McCorkell turned instead to those who were experiencing the same puzzling symptoms and frustrations, joining a support group for people with what would eventually be called long COVID. As they compared notes, McCorkell and a handful of others — many of whom had research experience — realized that the information they were sharing might be helpful not only for those with long COVID, but also for those looking to study the condition. So, they founded a non-profit organization, called the Patient-Led Research Collaborative (PLRC), to design, provide advice on and even fund basic and clinical research into long COVID and other chronic illnesses.
Four years on: the career costs for scientists battling long COVID
A survey run by the group and published in 2021 catalogued the more than 200 symptoms experienced by people with the condition (H. E. Davis et al. eClinicalMedicine38, 101019; 2021). It is seen by some as putting long COVID on the map. “They really jump-started the interest,” says Lucinda Bateman, a physician in Salt Lake City, Utah, who specializes in treating people who have long COVID and related conditions. “That was really a point from where more broad awareness arose.”
In the past few years, this study and similar patient-led efforts have helped to shape research programmes on long COVID and kick off some early clinical trials of therapies that might otherwise have gone unexplored. Many patient advocates see the efforts as crucial. They also think the results are more helpful for advancing the understanding of long COVID than the current findings from programmes funded by the US$1.15-billion RECOVER initiative led by the US National Institutes of Health (NIH). People with long COVID and their advocates have criticized the initiative for not always listening to the needs of people with long COVID.
Getting involved in research is challenging, given the symptoms of long COVID, but many patient advocates say they have no choice. “They’ve got you over a barrel,” says Margaret O’Hara, who coordinates patient involvement in research for a National Health Service hospital trust in England. O’Hara is on medical leave owing to long COVID. Referring to the research, she says: “You have to do it, because you are the one who is going to suffer for it if you don’t, but at the same time, you’re in bed sick.”
A plethora of symptoms
The PLRC’s survey of long COVID symptoms was the first major research study of the condition. The premise was simple enough: authors surveyed almost 3,800 people in 56 countries, many of whom were members of various long COVID support groups worldwide, including the network Body Politic, from which the PLRC originated. When the authors analysed the data, they found scores of symptoms in at least ten organ systems.
The study showed that the most prevalent problems were fatigue, post-exertional malaise — a worsening of symptoms after exertion — and the cognitive dysfunction that came to be referred to as brain fog. Nearly 86% of participants reported relapses triggered by exertion; 87% said fatigue was a main symptom; and 88% reported brain fog, with no differences in cognitive issues across age groups.
NIH launches trials for long COVID treatments: what scientists think
The paper has amassed more than 1,000 citations, been mentioned in some 60 policy statements and is widely considered a seminal paper in long COVID research, owing to its in-depth analysis. For McCorkell, however, its impact is more fundamental. “What we demonstrated with the survey is that patients can lead high-quality research, and that it’s really necessary in order to have the most comprehensive look at a condition.”
The achievement is especially notable considering that the study was conducted by unpaid volunteers, most of whom identify as disabled, and it received no financial support. By contrast, many long COVID research initiatives have tended to focus on a subset of symptoms, which comes with the risk of missing the bigger picture, says McCorkell.
“There’s a lot of complexity in these illnesses, and I think it’s really important to embrace these complexities,” says Beth Pollack, a research scientist at the Massachusetts Institute of Technology in Cambridge, whose work focuses on understanding long COVID and other infection-associated chronic illnesses. With conditions that have a range of symptoms, and for which there is only limited research, building a knowledge base starts by listening to patients’ stories and capturing the nuances of their conditions, Pollack says.
Desperate measures
In early 2020, Martha Eckey, a pharmacist in Minneapolis, Minnesota, developed a COVID-like illness. She experienced a crushing fatigue that no amount of sleep could relieve, and was bedbound for days at a time. The physicians she went to for help had no answers. In desperation, Eckey turned to the online community of people with long COVID.
She found people trying treatments from prescription medications to over-the-counter supplements. But the effectiveness of these was restricted largely to personal anecdotes.
In the hope of getting a more comprehensive, systematic understanding of what worked, Eckey designed a survey called TREAT ME, which asked people with long COVID and those with myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), about their experiences, including whether they had tried any of a list of 150 medications and supplements. More than 4,000 people responded.
Martha Eckey’s TREAT ME survey found overlap between treatments people were using for long COVID and for other chronic conditions.Credit: John Karp
Eckey found overlap with other chronic conditions. Some treatments revealed by the survey as most effective for long COVID were drugs such as beta blockers and the heart-failure medication Corlanor (ivabradine). These are sometimes used to treat postural orthostatic tachycardia syndrome, a nervous-system disorder that can be triggered by COVID-19. Eckey also found that a number of individuals reported relief after taking naltrexone, a non-opioid drug for treating substance-use disorder. When taken at low doses, it has anti-inflammatory and pain-relieving properties.
Physiotherapist David Putrino, who specializes in rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai in New York City, says that the TREAT ME survey captured something both simple and profoundly important. “It’s a very fundamental question of, ‘what are you taking that’s helping right now?’” he says. The results have helped to guide his research on long COVID.
Listening to patients
TREAT ME attracted the attention of scientists and research foundations, who soon realized that this information could help to shape their efforts. One was the Open Medicine Foundation, a non-profit organization in Agoura Hills, California, that studies infection-associated chronic illnesses such as long COVID and ME/CFS.
Linda Tannenbaum, a clinical laboratory scientist, founded the Open Medicine Foundation in 2012 in response to the difficulties she encountered while seeking a diagnosis and treatment for her daughter, who has ME/CFS. Its first double-blind, randomized, placebo-controlled clinical trial will explore low-dose naltrexone (LDN) and another drug, pyridostigmine, which is used to treat an autoimmune disorder that affects voluntary muscle movements. The medications will be tested separately and in combination. Tannenbaum credits TREAT ME for helping to shape which symptoms will be assessed during the trial.
“The reason we are doing LDN as our first trial is that patients asked for it,” she says. TREAT ME also showed that many people with long COVID said that LDN helped to reduce brain fog (see go.nature.com/3qy2tpj). Given these results, the Open Medicine Foundation also incorporated parameters in the trial to test cognitive function. Both LDN and pyridostigmine have been used to treat long COVID, but as many patients report, physicians are often reluctant to prescribe these drugs because of a lack of formal, randomized, controlled trials showing their effectiveness. “Doctors are very hesitant to go outside approved, or at least medically tested, medications,” says Bateman. In her experience, insurance companies also won’t pay for these medications for people with ME/CFS and long COVID without strong evidence to support their use.
Many patient advocates say that there is insufficient clinical research on the kinds of drug that people are already using. In February, the RECOVER initiative received a further $515 million over the next 4 years to test more interventions and investigate the long-term effects of a SARS-CoV-2 infection. But so far, the only trials it has begun are of the antiviral medication Paxlovid (nirmatrelvir and ritonavir), which started enrolling patients in July 2023, and of ivabradine and intravenous immunoglobulin, which recruited its first participants last month.
Lauren Nichols, a long COVID patient advocate, helped to lead the Body Politic support group.Credit: Lauren Owens Lambert/Reuters
“There are a lot of clinical trials that are focused on more behavioural and on non-pharmaceutical interventions, and that is really not a priority to the patient community,” McCorkell says. “It is a misunderstanding of how severe the condition is, and how much of an impact on people’s quality of life it has taken.”
A spokesperson for RECOVER told Nature that the clinical trial of a computer game has already started enrolling participants and that the exercise trial is still scheduled to begin. They emphasized that these are accessible interventions, which might help some people who are affected, given the wide range of symptoms. They also said that moving these trials forwards will help in developing the framework for testing more treatments.
Lifting the fog
In the weeks after her initial COVID-19 infection, Hannah Davis found herself struggling with severe brain fog, to the point at which she could barely string two sentences together. Davis, who at the time was working as a data analyst and artist, with a particular focus on addressing biases in machine learning, kept waiting for her cognitive function to go back to normal, only for it never to return. “I had, and continue to have, terrible, terrible cognitive impairment,” says Davis, who is one of the co-founders of the PLRC.
Long COVID exercise trials proposed by NIH raise alarm
Brain fog is having a significant impact on people’s livelihoods, says Wes Ely, a physician-scientist who works in intensive care at Vanderbilt University Medical Center in Nashville, Tennessee. People with long COVID have a form of cognitive impairment that is often “like mild and moderate dementia”, he says.
Ely, who studies treatments for Alzheimer’s disease and related dementias, decided in 2020 to expand into studying the cognitive impairments associated with long COVID. He quickly recognized that the condition is deeply complex, with symptoms that go beyond cognitive impairment.
To gain a comprehensive understanding of the phenomenon, he turned to the patient community, eventually recruiting Davis and Jaime Seltzer, director of scientific and medical outreach at the non-profit organization ME Action in Santa Monica, California. Together, they drafted a clinical trial to test the medication baricitinib, an immunomodulatory drug that is used to treat rheumatoid arthritis and alopecia areata, and acute COVID-19 infections. “I wanted to learn from people who are living with this disease,” says Ely.
The trio, along with other US investigators, designed a 550-person clinical trial of baricitinib as a potential treatment for long COVID. The trial has now been funded by the NIH and will start enrolment later this year.
From Seltzer’s perspective, an effective collaboration between patients and scientists can help both sides equally, because it leads to more effective and targeted research. “We have the resources to help you do what you do even better,” Seltzer says. The lived experiences of patients can shape research priorities in several key ways, she says. These include finding the most efficient way to allocate limited funds on the basis of symptom burden; offering context on the prevalence and severity of symptoms; and identifying how the trial design can capture improvement most effectively. All of this can help lead to faster breakthroughs in treatments, which is of benefit to both patients and researchers, Seltzer says.
Microclot mystery
In late autumn 2022, McCorkell flew to New York City to participate in a trial being conducted by Putrino and his team. This study aimed to look for the presence of tiny blood clots, called microclots, in people with long COVID. It is thought that these cause symptoms such as fatigue and brain fog by impairing blood flow to the brain and body. There are still a lot of unknowns about microclots, including how many people with long COVID have them, how they form and whether the association is causal.
Long-COVID treatments: why the world is still waiting
McCorkell gave blood samples that were analysed using fluorescent microscopy, which confirmed she had microclots. McCorkell says it was “a wake-up call”. Until that point, she had been managing her symptoms mainly by avoiding overexertion. But the presence of the clots suggested to her that there might be active damage happening to her body. So, she started taking supplements that TREAT ME survey respondents reported as helpful.
Eckey’s results, which have not yet been published in a peer-reviewed journal, show that of 668 respondents with long COVID, between 40% and 70% found some symptom relief when taking the supplements nattokinase, serrapeptase or lumbrokinase, individually or in combination (see go.nature.com/43xgyoq).
When Putrino saw these results, he decided it was crucial to conduct clinical trials of the supplements. He expects to begin a 120-person study on lumbrokinase in the coming months, and has involved patients at every step of its development.
“Every research trial that we run, we involve the patient community in the protocol,” Putrino says. This includes taking their advice on what trials should be prioritized, what symptoms to assess, how many clinic visits to require and what the testing environment should be like, to minimize the risk of exacerbating their symptoms, he says.
McCorkell says that the supplements she’s been taking have improved her general function by about 10%. Whereas that might not sound like much, she feels it is meaningful progress. Although the long COVID research has been difficult, she sees no other option but to stay involved. “We’re driven by desperation, out of improving our own quality of life.”
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Surgeons at Xijing Hospital in Xi’an, China, performed the first transplantation of a non-human liver into a human body.Credit: Xijing Hospital, Air Force Medical University in Xi’an China
Surgeons in China say they have transplanted a pig liver into a person’s body for the first time. With consent from the man’s family, the clinically dead patient received a liver from a pig that was genetically modified to prevent the recipient from rejecting the pig organ. The surgeons say the pig liver secreted more than 30 millilitres of bile every day, and the colour and texture of the liver remained normal after 10 days. In January, a US team conducted a similar experiment with a pig’s liver located outside a person’s body, and there have been further experiments with genetically modified pig kidneys and hearts.
Stellar detectives have identified seven stars that recently gobbled up a rocky planet. The planets seem to have been eaten during their stars’ relatively stable main-sequence period. If this is true, it means these systems have continued to be chaotic long after their formation, with planets disintegrating or falling into their star, says astronomer Johanna Teske. “It’s an inference at this point. We need to look at these systems in more detail.”
The number of researchers who have left Russia since it invaded Ukraine in February 2022, according to an estimate based on researchers’ ORCID identifiers. (Nature | 5 min read)
A slew of studies have identified how inflammation in the brains of people with COVID-19 might explain neurological symptoms such as loss of smell, headaches and memory problems. Growing evidence suggests that the immune response triggered by the virus leads indirectly to brain inflammation. One study found that people with long COVID and ‘brain fog’ had a leakier blood-brain barrier, which might let in molecules that cause inflammation.
Indian biotechnology company ImmunoACT is producing a much cheaper version of a cancer treatment known as chimeric antigen receptor (CAR) T-cell therapy. A single treatment of NexCAR19 costs between US$30,000 and $40,000 — a tenth of the price of comparable products now available. The safety profile also appears to be better than some US-approved CAR-T products. NexCAR19 is now being used to treat blood cancers in hospitals across India. “These are people for whom all other treatments have failed,” says immunologist Alka Dwivedi.
For 15 years, geoscientists have been involved in a complicated technical process to determine whether human impacts on Earth amount to a new geological epoch: the Anthropocene. This week, following a controversial vote and challenge, the final verdict has arrived from the International Union of Geological Sciences: we are not in a new epoch. The current lack of agreement on a start date should not detract from the Anthropocene as a concept, says a Nature editorial. The reality is that humans are leaving a discernible fingerprint on Earth systems.
AI image generators can amplify biased stereotypes in their output. There have been attempts to quash the problem by manual fine-tuning (which can have unintended consequences, for example generating diverse but historically inaccurate images) and by increasing the amount of training data. “People often claim that scale cancels out noise,” says cognitive scientist Abeba Birhane. “In fact, the good and the bad don’t balance out.” The most important step to understanding how these biases arise and how to avoid them is transparency, researchers say. “If a lot of the data sets are not open source, we don’t even know what problems exist,” says Birhane.
Invasive ant species such as the Argentine ant (Linepithema humile) have conquered the land so thoroughly that “it can seem as if the spread of global trade was an Argentine ant plot for world domination”, writes science journalist John Whitfield. He explores what makes these insects so successful, their effects on ecosystems and the temptation to compare their spread with humanity’s own power struggles. Ants “speak to life’s ability to escape our grasp, regardless of how we might try to order and exploit the world”, writes Whitfield. “There’s something hopeful about that, for the planet, if not for us.”
The psychoactive drug ketamine is increasingly being used to treat depression and other mood disorders, including by high-profile users such as entrepreneur Elon Musk or actor Matthew Perry. More than 40 clinical trials support its effectiveness in treating severe depression. But neuropsychopharmacologist David Nutt warns that those taking it need careful supervision. (Nature | 5 min read)
People with long COVID often struggle to get sufficient support in the workplace; researchers are no exception.Credit: Vuk Valcic/SOPA Images/Shutterstock
Abby Koppes got COVID-19 in March 2020, just as the world was waking up to the unprecedented scale on which the virus was spreading. Her symptoms weren’t bad at first. She spent the early lockdown period in Boston, Massachusetts, preparing her tenure application.
During that summer of frenzied writing, Koppes’s symptoms worsened. She often awoke in the night with her heart racing. She was constantly gripped by fatigue, but she brushed off the symptoms as due to work stress. “You gaslight yourself a little bit, I guess,” she says.
Soon after Koppes submitted her tenure application in July, she began experiencing migraines for the first time, which left her bedridden. Her face felt as if it was on fire, a condition called trigeminal neuralgia that’s also known as suicide disease because of the debilitating pain it causes. Specialists took months to diagnose her with a series of grim-sounding disorders: Sjögren’s syndrome, small-fibre polyneuropathy and postural orthostatic tachycardia syndrome. To make time for the litany of doctors’ appointments, Koppes took a six-month “self-care sabbatical”.
It’s a bit of a blur, she says, but Koppes, a biochemical engineer at Northeastern University in Boston, describes September 2021 to April 2023 as a dark period in her life. Fortunately, she was buoyed by one monumental victory that preceded it: she was granted tenure in summer 2021.
Abby Koppes changed her research focus to study her own experience of long COVID.Credit: Adam Glanzman/Northeastern University
However, other academic researchers with long COVID might not count themselves so lucky. Koppes’s experience has compelled her to speak up for other researchers with the condition. It needn’t spell the end of an academic career, provided institutions step up to help. Nature spoke to researchers living with long COVID to find out how they manage the illness amid the pressures of academic research. (Many requested anonymity for privacy or for fear of repercussions on their careers and reputations.) They describe new realities that include budgeting for periods of fatigue and negotiating adjustments such as flexible working arrangements — an area, they say, in which academia can do better.
When academia meets long COVID
Koppes is one of at least 65 million people worldwide to develop long-term health problems after contracting the virus SARS-CoV-2. The World Health Organization defines long COVID as a suite of symptoms lasting two months or longer, continuing or occurring three months after the initial infection.
Collection: Coronavirus and scientific careers
Common symptoms of long COVID include cognitive impairment, fatigue and immune dysregulation. Weak or overburdened health-care systems in some nations mean many people who have the condition are left without appropriate care.
Moreover, in the cut-throat world of academia, in which it is the norm to push oneself through graduate training and the postdoctoral stage, and as an early-career academic, long COVID throws up barriers for those seeking permanent positions, such as the promised land of tenure.
It could also squeeze diversity out of the talent pool — studies have shown that long COVID tends to disproportionately affect women and people of colour. “Women are already under-represented in higher roles,” says Natalie Holroyd, a computational medicine researcher with long COVID at University College London. “Is this going to exacerbate existing inequality?”
Scientists count the career costs of COVID
“Getting tenure was so profoundly destructive to my health that it prepared my body for severe long COVID,” one Latina researcher in the humanities tells Nature. “I feel like my academic job demands my death.”
Researchers with long COVID often face extra administrative burdens: dealing with the mountains of paperwork for disability claims and workplace-accommodation requests. These tasks can feel like a part-time job in their own right. “Not only are we trying to get all the same work done with many fewer functional hours, but we also have more work to do,” one US-based biology researcher says. “That doesn’t even count all of the extra hours that we have to spend dealing with getting health care.”
There’s also financial pressure. Researchers might feel the need to soldier on to continue to receive a steady income and, in many cases, employer-provided health insurance. The most vulnerable individuals are graduate students and postdoctoral scholars on temporary contracts. International early-career researchers’ visa status can be contingent on working full-time.
In some cases, seeking accommodations can feel out of reach. “I did not go up to anybody and say, ‘Hey, I’ve been dealing with this the entire two years. Can we do something about it?’” says Priya (not her real name), a master’s student with chronic post-COVID-19 health problems at one of the Indian Institutes of Science Education and Research. Organizing a community to advocate for a better learning and research environment takes time, effort and money. Convinced that the university can’t do much, Priya is resigned to bearing her poor health alone. “There are definitely other people here that have similar issues, but I don’t think there’s been a dialogue about it.”
Pandemic productivity loss: how scientific institutions should support academic mothers
Academics with long COVID also face societal ignorance about the condition, with several of those Nature spoke to reporting that they were mainly left to fend for themselves or to navigate workplace accommodation policies that aren’t tailored for long COVID. Many researchers conceal their illness for fear of stigma. Even with understanding colleagues, people with long COVID say they’re exhausted from constantly advocating for their needs and educating others about the condition.
Because some symptoms can be invisible, colleagues might negatively judge a co-worker’s performance or ability to participate. When Sarah (not her real name) started her assistant professorship at a US university, colleagues who were aware of her condition would occasionally tell her that she “looked good” during a meeting. “But it’s because I had very carefully managed my day,” she says. To be able to attend an hour-long meeting at the height of her symptoms, Sarah says she would sleep for two hours beforehand, then for another two afterwards to recuperate. “They don’t realize that there are four hours on either side that were devoted to making it possible.”
The need for extra rest can leave those with long COVID little time for pursuing career-advancing opportunities, especially travel. And because reinfection can exacerbate symptoms, crowd-facing activities aren’t safe, either, when masking is not required.
Sociologist Kerstin Sailer had to redefine what it meant to be a researcher living with the disabilities that come with long COVID.Credit: Beatrix Fuhrmann
Many high-achieving researchers with long COVID say that one of their biggest struggles is the loss of their identities that had been pegged to their cognitive abilities and productivity. Often, they learnt the hard way that pushing themselves beyond their limits would only cause them to crash later. “It took me a while to recognize that I am now a disabled academic,” says Kerstin Sailer, a sociology researcher at University College London. She had “to gather around and find my own kind of inner strength and redefine what it means to be me”.
But Sailer and others are a testament to the fact that long COVID need not signal a career dead end. With the right support, affected academics can still thrive.
Accommodations and flexibility
Researchers living with long COVID have found ways to adapt, often relying on assistance from peers. Koppes co-advises all of her students with her husband, an academic at the same university, which is helpful for the days she’s off sick. Other long-haulers have formed online support groups or leaned on collaborators to help them to cross project finishing lines. Kathleen Banks, a public-health doctoral student with long COVID at Boston University in Massachusetts, has an informal dissertation coach who holds her accountable for meeting graduation milestones without pushing her too hard.
Researchers say that the most important form of support is that offered by a compassionate supervisor, be it a department chair or a research adviser. They advise looking for someone who prioritizes your health and doesn’t put undue pressure on you to perform.
Academia’s ableist culture laid bare
Holroyd says she’s grateful for having had the same supportive adviser since her PhD days. “He kept reassuring me that the work that [I’m] putting out is fine, it’s enough,” she says of her now-postdoctoral supervisor. “I’m unlikely to find that level of support elsewhere.”
Ideally, supervisors will also fight for needed accommodations. These can include having a private office, being able to work from home, teaching remotely and having a flexible schedule to deal with an unpredictable ailment.
Employers should also recognize that accommodations, such as virtual working, aren’t one-size-fits-all. Jane (not her real name) is a US-based researcher in the social sciences who developed mast-cell activation syndrome after a COVID-19 infection. In her case, this causes life-threatening allergic reactions to synthetic chemicals in scented products. She requested a high-efficiency particulate air filter for her classroom, but her institution recommended that she teach remotely instead.
However, as other classes at her institution returned to in-person formats, Jane says she noticed that students preferred those to virtual courses such as hers. She’s nervous about the impact this might have on the teaching evaluations that count towards tenure. She has proposed that her institution establish a fragrance-free policy for her office building, but her employers, although receptive, have declined to help her enforce the rules. “It felt like they threw everything at me to advocate for myself,” Jane says. “They basically proposed the remote option as an alternative to all the things that I had requested.”
In many countries, disability laws require employers to make reasonable allowances for disabled workers. Of course, the word ‘reasonable’ is open to interpretation. Not everyone has found workarounds for their job. One mathematics PhD student in the Netherlands quit his programme in his final year after contracting long COVID. And some scholars have pivoted to focus on less physically demanding and more remote-friendly research fields, choosing computational over experimental work, for example, to allow them to sidestep significant hands-on labour.
Many institutions have offered employees with long COVID tenure-clock pauses, deadline extensions and emergency health-related funding. Advocates welcome these short-term support measures, but say more needs to be done. Medical experts don’t know how long the condition might last, so academia needs to formulate long-term policies.
Without such policies, informal arrangements can signal to those with long COVID that they’re a burden. “My experience with the accommodation system has been [that] it just comes down so much to having a supportive principal investigator” to back you up, says one graduate student at a major US university who has long COVID. “That’s just not how it should be.”
Culture shift
Some advocates are calling for a culture that champions workplace accessibility for all: universal design. The concept aims to shift the onus of advocating for particular needs away from the individual. Universal design measures include — by default — live captioning for video-call events and the taking of meeting notes to share with absentees. Researchers with long COVID also advocate for those organizing seminars and conferences to enable remote attendance options.
Brainstorming for these initiatives needs to be a community-wide process, says Emily Shryock, the director of the University of Texas at Austin’s Disability Cultural Center, a community hub for those who identify as disabled and their allies. She recognizes that there will always be tricky situations that have no easy answer. Nevertheless, the broader goal is to reach a middle ground between measures that aren’t required by law any more, such as mask mandates, and individual preferences. “That would be the hope — that every person would feel like they can ask for what they need and be supported in that request, even if, ultimately, they don’t get exactly what they want,” she says.
Postdoctoral fellow Sandra Schachat says being vulnerable to contracting long COVID means she is likely to seek remote-working opportunities next.Credit: Andrés Baresch
Universal design is just the first step; academic culture has a long way to go to becoming more inclusive. People like Holroyd choose to stay with trusted advisers so as not to risk working with someone less empathetic. Others are leaving academia altogether. “Why would I want to spend my entire career begging for safety measures that are essential to my survival?” asks Sandra Schachat, a postdoctoral researcher and Schmidt Science Fellow at the University of Hawaii at Manoa. She has dodged COVID-19 so far, but she has an autoimmune disease and knows it makes her vulnerable to the infection’s chronic fallout. Although she says her current lab is “perfect”, she doesn’t trust the larger academic world to protect people like her. So, when her fellowship ends, she plans to explore a career in industry that will allow her to work remotely.
In academia’s rigid research-assessment system, which is based on the quantity of publications and invited talks a person clocks up, people with chronic illnesses find it incredibly hard to compete. Jane, the social scientist, says her university refuses to make exceptions to the tenure policy for those with long COVID. Other affected researchers call for academic success to be reimagined.
Chris Maddison says long COVID bolsters calls for more flexible research assessments.Credit: Dan Komoda/Institute for Advanced Study
“I do think that [universities] should broaden what they consider to be impact,” says Chris Maddison, a machine-learning researcher with long COVID at the University of Toronto, Canada. That could mean acknowledging different contributions towards society as being equally valuable. For example, in addition to papers published, his field could also count contributions such as releases of scalable, machine-learning prototypes. Nevertheless, Maddison admits that finding the solution to equitable academic assessment isn’t simple. “Maybe long COVID is just one other impetus to say we need to really solve this problem.”
On an individual level, long COVID has also served as a wake-up call to some researchers in relation to their taxing lifestyles. “It’s really forced me to re-evaluate my relationship with stress and my work–life balance,” says one postdoc in the United Kingdom. Now, she is diligent about pacing herself and feels much less guilty for taking breaks. “This experience has helped me develop healthier habits and skills that I’ll carry with me even after I recover.”
On the flip side, the rigours of academic research have also helped to prepare these scholars for the ups and downs of long COVID. “Science has also trained me [to have] resilience, persistence, patience,” says Sarah. “These are helpful qualities when dealing with chronic conditions.”
Koppes agrees. Inspired by her own conditions, she has shifted her research towards the autoimmunity and neurology of long COVID symptoms to interrogate her experience.
For now, Koppes is celebrating the small victories in her slow recovery: being able to walk the dog or take public transport instead of relying on car rides. On her wall at home hangs a reproduction of a painting by the impressionist artist Edward Henry Potthast titled Wild Surf, Ogunquit, Maine. It depicts a beach that she and her husband frequented pre-COVID-19 — a reminder, she says, not of everything she’s lost, but of what she might one day return to.
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The Nigerian health ministry has been told to investigate reports of deaths in the northeastern state of Gombe (pictured).Credit: Tolu Owoeye/Shutterstock
Nigeria’s National Assembly has instructed the country’s health ministry to investigate a “strange disease” said to have killed more than two dozen people in the northeastern state of Gombe. The World Health Organization says that there have been three deaths, resulting from confirmed cases of meningitis. The case highlights the importance of thorough disease-surveillance systems and the need for timely communication, say researchers.
The UK science minister Michelle Donelan has apologized and paid damages for accusing two researchers on a UK Research and Innovation panel of “extremist” views on the Israel–Hamas conflict. More than a dozen researchers resigned from the United Kingdom’s national funder after it dissolved the panel in response to the minister’s demand.
For the first time, an influenza virus has been eliminated from the human population through non-pharmaceutical interventions. The public-health protections brought in during the COVID-19 pandemic — such as wearing a mask, social distancing and better ventilation — seem to have eliminated the influenza B/Yamagata lineage; no cases have been confirmed since March 2020. In September, the World Health Organization recommended that countries no longer include Yamagata-lineage antigens in flu vaccines, and US Food and Drug Administration advisors have now voted to remove it from flu jabs in the United States.
China has updated its Early Warning Journal List — a list of journals that are deemed to be untrustworthy, predatory or not serving the Chinese research community’s interests. The latest edition includes 24 journals and, for the first time, takes note of misconduct called citation manipulation, in which authors try to inflate their citation counts. Scholarly literature researcher Yang Liying heads up the team that produces the influential list and spoke to Natureabout how it’s done.
Tracking malaria infections in lizards in a rainstorm? Recording beetle species in a dusty cornfield? Sometimes a pencil and notebook still outperform a computer or smartphone in the field. Other data might be immortalized in ledgers crowded with historical handwriting. For those times, Nature has compiled five tips for getting handwritten data digitized into a form that can be analysed.
In Atlas of the Senseable City, architect-researchers Antoine Picon and Carlo Ratti delve into the impact of digital maps on human society. “Ancient Romans had two words for city: ‘urbs’, the physical environment, and ‘civitas’, the community of citizens,” says Ratti. “For the first time, technology allows us to visualize and understand civitas: how people move in space, how they connect, and also how they segregate … Architects and urban planners can now take into account the civitas rather than just the urbs.”
Figure 1 | Vertebrate adaptations to life on land.a, Approximately 350 million years ago, some animals living in the water were on the verge of evolving to live on land. b, This transition required the innovation of forming hard-shelled eggs that enabled embryos to develop outside an aquatic environment. Other features suited to life on land included protective scales. It is plausible that embryonic skin underwent rapid patterning into spot-like areas corresponding to sites where scales would subsequently form. On hatching, such developing scales probably hardened rapidly by cell differentiation in a manner distinct from that of the surrounding tissue. Embryonic patterning and post-embryonic maturation might give rise to mechanically resilient yet flexible waterproof skin, containing scales and offering protection against damage by ultraviolet light. This hypothetical scenario is supported by observations of highly patterned mini scales in fossilized skin samples, reported by Mooney et al., attributed to 285-million-year-old early land-dwelling vertebrates called amniotes. c, Scales evolved that fully covered the body of early amniotes, such as members of the Varanopid family of amniotes.
Don’t chuck that cheddar or bin that Brie until you’ve read this handy guide to when you should throw out mouldy cheese — the answer is ‘hardly ever’. “Even though we’ve been taught to fear mould, all of cheese is mould,” says cheese specialist Anne-Marie Pietersma in a statement that will forever be burned into my mind. In a nutshell, the harder the cheese, the less you need to worry about just cutting off the bad bits and chowing down.
While I indulge in some gorgeous gorgonzola, why not send me your feedback on this newsletter? Your e-mails are always welcome at [email protected].
Landmark study contradicts misinformation about brain development and conditions like autism in children.
The COVID vaccine is safe to administer during pregnancy, reports UC San Francisco in an important finding on the safety of the vaccine in infants — despite widespread fear and misinformation.
The study, published in JAMA Pediatrics, is the first scientific inquiry into whether infants are at increased risk of neurodevelopmental impairments as a result of maternal vaccination.
The landmark study of more than 2,200 infants from across the country found that in utero exposure to the vaccine caused no abnormal delays when the infants were tested at 12 months and again at 18 months.
“This is a very reassuring finding — pregnant women have been facing unanswered questions around COVID vaccinations for several years,” said first author Eleni Jaswa, MD, MSc, a reproductive endocrinologist and fertility specialist at UCSF Health, noting the investigation started in April 2020. She is also an assistant professor in the UCSF Department of Obstetrics, Gynecology & Reproductive Sciences.
First meaningful evidence of maternal vaccination safety during pregnancy
Although pregnant women are considered at increased risk of severe illness with COVID-19, some chose not to get the COVID vaccine due to safety concerns around potential risks to their unborn children.
Some 34% of the participants in the study were vaccinated in the first trimester, about 45% in the second trimester, and nearly 21% in the third trimester. They were asked to complete a 30-item questionnaire assessing whether their infants performed expected milestones.
After adjusting for such factors as maternal age, race, ethnicity, education, income and maternal depression, the researchers found no difference in the risk of infant neurodevelopment at either 12 months or 18 months. They noted an increased risk of delay among male infants at 12 months but the difference was not observed at 18 months.
The study is ongoing.
“Understandably, there’s been concern about the potential impact of maternal vaccination on offspring,” said senior author Heather Huddleston, MD, a UCSF Health reproductive endocrinologist and director of the UCSF Polycystic Ovary Syndrome Clinic (PCOS).
“Despite early safety data as well as recommendations from physicians and health organizations, vaccine hesitancy is still preventing universal use,” she said. “To this day, misinformation continues to abound. People are concerned about such issues as brain development and conditions like autism in children. This is the first meaningful evidence into the safety of vaccination from the standpoint of early offspring neurodevelopment.”
Co-authors: All from UCSF, the paper’s co-authors are Marcelle Cedars, MD; Karla Lindquist, PhD; Somer Bishop, PhD; Young-Shin Kim, MD, MPH, PhD; Amy Kaing, MD; Mary Prahl, MD; Stephanie Gaw, MD, PhD; Jamie Corley, BS; Elena Hoskin, MS; Yoon Jae Cho, MD; and Elizabeth Rogers, MD.
mRNA vaccines developed against the spike glycoprotein of severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2), displayed remarkable efficiency in combating coronavirus 19 (COVID-19). These vaccines work by triggering both cellular and humoral immune responses against the spike protein of the virus. Cellular immunity may play a more protective role than humoral immunity to variants of concerns (VOC) against SARS-CoV-2, as it targets the conserved regions of spike protein and possibly cross-reacts with other variants.
Since a single spike epitope is recognized by multiple T-cell clones, the mRNA vaccination-induced T-cell response may consist of multiple spike-reactive clones. Thus, it is important to understand the mechanism of mRNA vaccination-induced cellular immune response. However, to address this clonal-resolution analysis on T-cell responses to mRNA vaccination has not been performed yet.
To bridge this gap, a team of researchers, led by Associate Professor Satoshi Ueha, including Professor Kouji Matsushima from the Tokyo University of Science (TUS), Japan, Mr. Hiroyasu Aoki from the University of Tokyo, and Professor Toshihiro Ito from Nara Medical University, aimed to develop a kinetic profile of spike-reactive T-cell clones during repetitive mRNA vaccination. For this, they performed a longitudinal TCR sequencing on peripheral T cells of 38 participants who had received the Pfizer vaccine from before the vaccine to after the third vaccination and then analyzed the single-cell gene expression and epitope specificity of the clonotypes.
Their findings, published in Cell Reports on March 7, 2024, revealed that while the primary T-cell response of naïve T cells generally peaked 10-18 days after the first shot, expansion of “early responders” was detected on day 7 after the first shot, suggesting that these early responders contain memory T cells against common cold coronaviruses. They also found a “main responder” that expanded after the second shot and did not expand early after the first shot and a “third responder” that appeared and expanded only after the third shot.
By longitudinally tracking the total frequency of each response pattern, it was observed that, after the second shot, a shift among the clonotypes occurred, wherein the major population changed from early responders to main responders, suggestive of a shift in clonal dominance. A similar shift of responding clones was also observed in CD4+ T cells.
Expanding upon the research process, Prof. Ueha says, “We next analyzed the phenotype of main responders after the second and the third vaccination. The results showed that the main responders after the second and third shots mostly consist of effector-memory T cells (TEM), with more terminally differentiated effector memory-like phenotype after the third shot.”
The researchers then examined the repertoire changes of main responders, revealing that the expansion of main responders, which occurred after the second shot, diminished following the third shot, and the clonal diversity decreased and was partially replaced by the third responders. This may potentially mean that the third vaccination selected better-responding clones.
Due to the vaccination-induced shift in immunodominance of spike epitopes, the study supports the inter-epitope shift model. In addition, there were intra-epitope shifts of vaccine-responding clonotypes within spike epitopes.
Prof. Ueha explains the significance of these results, “Our analysis suggests that T cells can “re-write” themselves and reshape their memory populations after successive vaccinations. This re-writability not only maintains the number of memory T cells but also maintains diversity that can respond to different variants of pathogens. Moreover, by tuning the replacement of memory cells, more effective vaccines can be developed that can also be tailored to an individual’s unique immune response.”
Overall, this study provides important insights into mRNA vaccine-induced T-cell responses, which will be crucial for developing next-generation vaccines for more effective and broad protection against viruses.
