Through a quirk of anatomy, women are especially prone to urinary tract infections, with almost half dealing with one at some point in their lives.
Scientists have been trying to figure out for decades how bacteria gain a foothold in otherwise healthy people, examining everything from how the microbes move inside and stick to the inside of the bladder to how they deploy their toxins to produce uncomfortable and often painful symptoms.
Research published in PNAS examines how the bacteria Escherichia coli, or E. coli — responsible for most UTIs — is able to use host nutrients to reproduce at an extraordinarily rapid pace during infection despite the near sterile environment of fresh urine.
Investigators working in the lab of Harry Mobley, Ph.D., at the University of Michigan Medical School began by looking at mutant strains that weren’t as good at replicating in mouse models to identify bacterial genes that may be important for establishing infection.
Doing so, they identified a group of genes controlling transport systems as critical.
“When bacteria need something to grow, say an amino acid, they can get it in two ways,” explained Mobley, who is the Frederick G. Novy Distinguishes Professor of Microbiology and Immunology.
“They can make it itself, or they can steal it from their host using what we call a transport system.”
Their previous gene expression screen revealed that nearly 25% of bacterial genes were dedicated to replication tactics including transport systems for specific amino acids, which E. coli use to bring in thousands of molecules per second, said Mobley.

First author Allyson Shea, Ph.D., a former member of Mobley’s lab and now assistant professor of Microbiology and Immunology at the University of South Alabama, cross referenced a library of transport proteins from E. coli against other species of UTI pathogens to see which were important for infection. She discovered that a type of transporter called ABC (for ATP-binding cassette) transporters appeared to be critical.
Then using organ agar made from the mouse urinary tract, she confirmed that ABC transporters were essential for infection. Many bacteria strains lacking these nutrient import systems were defective for growth on bladder and kidney organ agar.
“It appears bacteria make an investment into these energy expensive ATP transport systems in order to have a higher affinity for the energy sources they are interested in,” said Shea.
“These systems are very, very good at getting nutrients inside the cell.”
The findings, Mobley notes, open avenues for the development of new therapeutics — which is especially important in an era of increasing antibiotic resistance.
“If you inhibit these transport systems, maybe you can inhibit the rapid growth of these bacteria,” he said.

Doing so won’t be easy, notes Shea, as bacteria have evolved multiple backups systems for this important class of transporters.
“What’s nice about this ATP-binding family is they all have an ATP binding subunit which gives the transport system the energy it needs to get nutrients across the cell membrane.”
This subunit could potentially be a target to make the entire family of transporters dysfunctional.
While this wouldn’t necessarily replace antibiotics, she says, it could slow down growth so that antibiotics and the host immune system could do a better job at stopping the bugs.

The first panoramic view of infection pathways in the human placenta has been created, which could highlight potential drug targets to develop pregnancy-safe therapies for malaria, toxoplasmosis and listeria, all diseases that can cause severe pregnancy complications.
Researchers from the Wellcome Sanger Institute, the University of Cambridge, the University of Dundee, and collaborators, used novel ‘mini placenta’ models to map the placental response to infections in early development. This work is part of the wider Human Cell Atlas consortium1, which aims to map every cell type in the human body to transform our understanding of health and disease.
The study, published today (3 May) in Cell Systems, focused on the pathways involved in malaria, toxoplasmosis, and listeria infection, all of which can cause pregnancy complications and miscarriage. It revealed that secondary inflammation may be the cause of pregnancy complications during these infections and uncovered that placental immune cells are likely to play a defensive role against pathogens.
Future work focusing on identifying potential drug targets in the pathways that cause complications during infection could inform the design of more directed therapies to tackle infections in early-stage pregnancies.
Infections during pregnancy are a major global health concern2 affecting millions of people around the world. These infections can potentially cause maternal death, sepsis, and pregnancy complications, including miscarriage, foetal developmental conditions, low birth weight, and stillbirth3.
Malaria, toxoplasmosis, and listeria are widespread infections that can lead to pregnancy complications. This is of particular concern in regions where these infections are more common. For example, in Sub-Saharan Africa and parts of Southeast Asia where the malaria parasite Plasmodium falciparum is endemic4.
The placenta acts as a selective barrier during pregnancy, which allows nutrients to cross from mother to baby while blocking pathogens and toxins.

However, the pathogens that cause toxoplasmosis and listeria can cross the placenta, and the parasite responsible for malaria can attach to the outside. The foetus is particularly vulnerable during early-stage development as the immune response is not fully established, meaning that the foetus relies heavily on the placental barrier for protection.
Despite the impact of infections during pregnancy, the pathways and mechanisms these infections use to cross the placenta are poorly understood, partly due to the limitations of laboratory models used and differences between humans and mice.
In the latest study from the Wellcome Sanger Institute and collaborators, the team established ex vivo explant models, or ‘mini placentas’ from human samples5, which allowed them to map the response to infection at single-cell resolution.
The researchers identified a type of foetal immune cell, known as a Hofbauer cell, that were activated in all three types of infection but in different pathways. This is the first time that placental immune cells have been shown to play a defensive role against pathogens in a model of the human placenta.
The team found that pathogens can infiltrate these immune cells. For example, T. gondii, the parasite that causes toxoplasmosis, is likely to use these immune cells to evade the ongoing immune response and travel around the body.
They also discovered that all three infections induced a general inflammatory response in the placenta which dysregulated placental functions. This suggests that secondary inflammation may be the cause of some pregnancy complications.

Targeting these inflammation pathways could lead to pregnancy-specific treatment for infections, which is not currently possible.
In addition to this, the ‘mini placenta’ models developed by this team can be used in future research to gain more insights into placental response to infections as well as wider placental changes during development.
Dr Regina Hoo, co-first author from the Wellcome Sanger Institute, said: “While infections during pregnancy have been known to cause complications, including miscarriage and stillbirth, very little has been known about the underlying mechanisms. Our research shows that even with pathogens that cannot cross the placenta, the secondary inflammation from the immune system may be responsible for disrupting foetal development. Identifying key processes involved with the inflammation pathway could help us develop pregnancy-specific treatments that minimise this in the future.”
Elias Ruiz-Morales, co-first author from the Wellcome Sanger Institute, said: “We discovered that placental immune cells called macrophages can protect the placenta against infections. This is the first time that placental immune cells have been shown to play a defensive role in early-stage pregnancy in humans, and that these immune cells can be hijacked by toxoplasma during infection. Understanding more about how the placental immune system works can help give new insights into pregnancy complications.”
Dr Marcus Lee, co-senior author from the Wellcome Sanger Institute, now at the University of Dundee, said: “Millions of pregnancies each year are potentially exposed to malaria, and understanding how the parasite adapts during infection and how the body responds will be important in improving outcomes. However, studying the interactions between pathogens and the human placenta is understandably incredibly difficult and therefore the development of new models, such as the placental tissue system we used in this research, are a much-needed step forward.” The Human Cell Atlas (HCA) consortium aims to map every cell type in the human body as a basis for both understanding human health and for diagnosing, monitoring, and treating disease. An open, scientist-led consortium, HCA is a collaborative effort of researchers, institutes, and funders worldwide, with more than 3,400 members from 101 countries across the globe. A, Seale. (2020) Recognising the burden of maternal infection worldwide. The Lancet. DOI: 10.1016/S2214-109X(20)30126-1 Chan MY, Smith MA. (2018) Infections in Pregnancy. Comprehensive Toxicology. DOI: 10.1016/B978-0-12-801238-3.64293-9. World Health Organization, World Malaria Report 2023. All tissue samples were obtained with written informed consent from all participants in accordance with ethics guidelines and regulations.

Researchers at Umeå University, Sweden, have discovered that how a special protein complex called the Mediator moves along genes in DNA may have an impact on how cells divide. The discovery may be important for future research into the treatment of certain diseases.
“We have gained in-depth knowledge of how cell division is controlled, which is important for understanding the causes of various diseases that are due to errors in cell division, such as various tumour diseases,” says Stefan Björklund, professor at the Department of Medical Biochemistry and Biophysics at Umeå University and lead author of the study.
In each cell there is a machinery called the ribosome. It uses DNA as a template to produce proteins, which are necessary for virtually all processes in the cell. First, however, the cells must make a copy of the instructions in the form of mRNA through a process called transcription.
The research team at Umeå University has discovered how the Mediator, a protein complex in the cell nucleus, can bind to DNA and interact with another protein complex, Lsm1-7, to regulate the production of proteins that make up the ribosomes. The study shows that when cells grow too densely, cell division slows down. When this happens, the mediator moves to the end of the genes where it interacts with Lsm1-7. This has the dual effect of both slowing down the reading of the genes and interfering with the maturation of mRNA. This, in turn, leads to a reduced production of ribosomal proteins and thus a slower cell division.
A possible direction of future research may be to study whether it is possible to control the position of the mediator, in order to inhibit rapid cell division, for example in tumours.
“We are still early in the research in the field, so more studies are needed before we can say that this is a viable path, but it is an exciting opportunity,” says Stefan Björklund.
The study has been conducted in yeast cells that serve as a good model when it comes to understanding basic mechanisms that work in a similar way in more complex systems such as animal and plant cells.

In a study published in PNAS, Umeå researchers describe a natural product-like molecule, Tantalosin, that inhibits interaction between two proteins in complexes that reshape membranes inside the cell. The findings lead to a deeper understanding of how membrane remodelling works in human cells and future development of new drugs.
“Our study is a good case to use small molecules as valuable chemical tools for understanding complex biological mechanisms. I am happy to coordinate a fantastic collaboration with colleagues in Umeå, Stockholm and Germany,” says Yaowen Wu, professor at the Department of Chemistry at Umeå University.
Membranes of cells are made of lipids and proteins, and they serve barrier functions for cells and intracellular organelles. Membranes of cells are highly dynamic mosaic-fluid structures that undergo constant reshaping. The endosomal sorting complex required for transport (ESCRT) is tasked with remodelling membranes inside the cell. The ESCRT machinery assembles at the site in the cell where membranes need deformation and then forms helical protein polymers that can contract and pinch off cell membranes.
Previously, Professor Yaowen Wu and his group, in collaboration with Professor Herbert Waldmann’s laboratory at Max Planck Institute Dortmund in Germany, identified a chemical molecule, Tantalosin, that induces a phenotype like autophagy — a self-eating process in the cell. Tantalosin is a synthetic molecule inspired by alkaloids from the medical plant Cinchona. They observed a very interesting phenomenon in the cell treated with Tantalosin and investigated further the molecular mechanism how Tantalosin works in the cell.
In collaboration with the chemical proteomics core facility at SciLifeLab in Karolinska Institute the team scrutinized potential cellular targets of Tantalosin.
“To our surprise, we found that none of the autophagy-related proteins were on the list of potential targets. However, IST1 protein in ESCRT complexes was identified and validated as the cellular target of Tantalosin. We were excited to work on deciphering this unexpected connection between ESCRT complexes and autophagy,” says first author Anastasia Knyazeva, who just recently completed her doctoral degree at the Department of Chemistry at Umeå University.
The researchers characterized the mechanism using a range of biochemical and cell biological methods. When they studied protein-protein interaction in solution, they found that Tantalosin completely stops the interaction between IST1 and its binding partner CHMP1B.

“We then took a closer look at these two proteins using a transmission electron microscope in collaboration with Kasturika Shankar, a PhD student from Lars-Anders Carlson’s lab at Umeå University. Intriguingly, Tantalosin disrupts the formation of ordered IST1-CHMP1B filaments,” explains Shuang Li, the paper’s co-first author and postdoctoral fellow at the Department of Chemistry at Umeå University.
Furthermore, the researchers looked inside the cell and found that Tantalosin rapidly disrupts the recycling of cell-surface receptors back to the cell surface. This property could be potentially beneficial for treating certain types of cancers that are driven by cell-surface receptors.
In this study, the researchers found that LC3 protein, which is usually a hallmark of autophagy, is linked to the endosomal membranes during Tantalosin treatment. Interestingly, the canonical autophagic degradation was not observed. Instead, they found that the process follows a noncanonical autophagy pathway.
“We believe that Tantalosin can be a unique molecule that facilitates understanding new functions of noncanonical conjugation of LC3 to endosomal membranes. We hope that further studies will reveal the role of LC3-membrane conjugation and its associated proteins in membrane deformation processes,” says Anastasia Knyazeva.

Evidence from archaeological sites in the medieval English city of Winchester shows that English red squirrels once served as an important host for Mycobacterium leprae strains that caused leprosy in people, researchers report May 3 in the journal Current Biology.
“With our genetic analysis we were able to identify red squirrels as the first ancient animal host of leprosy,” says senior author Verena Schuenemann of the University of Basel in Switzerland. “The medieval red squirrel strain we recovered is more closely related to medieval human strains from the same city than to strains isolated from infected modern red squirrels. Overall, our results point to an independent circulation of M. leprae strains between humans and red squirrels during the Medieval Period.”
“Our findings highlight the importance of involving archaeological material, in particular animal remains, into studying the long-term zoonotic potential of this disease, as only a direct comparison of ancient human and animal strains allows reconstructions of potential transmission events across time,” says Sarah Inskip of the University of Leicester, UK, a co-author on the study.
Leprosy is one of the oldest recorded diseases in human history and is still prevalent to this day in Asia, Africa, and South America. While scientists have traced the evolutionary history of the mycobacterium that causes it, they didn’t know how it may have spread to people from animals in the past beyond some hints that red squirrels in England may have served as a host.
In the new study, the researchers studied 25 human and 12 squirrel samples to look for M. leprae at two archaeological sites in Winchester. The city was well known for its leprosarium (a hospital for people with leprosy) and connections to the fur trade. In the Middle Ages, squirrel fur was widely used to trim and line garments. Many people also kept squirrels trapped wild squirrels as kits in the wild and raised them as pets.
The researchers sequenced and reconstructed four genomes representing medieval strains of M. leprae, including one from a red squirrel. An analysis to understand their relationships found that all of them belonged to a single branch on the M. leprae family tree. They also showed a close relationship between the squirrel strain and a newly constructed one isolated from the remains of a medieval person. They report that the medieval squirrel strain is more closely related to human strains from medieval Winchester than to modern squirrel strains from England, indicating that the infection was circulating between people and animals in the Middle Ages in a way that hadn’t been detected before.
“The history of leprosy is far more complex than previously thought,” Schuenemann said. “There has been no consideration of the role that animals might have played in the transmission and spread of the disease in the past, and as such, our understanding of leprosy’s history is incomplete until these hosts are considered. This finding is relevant to today as animal hosts are still not considered, even though they may be significant in terms of understanding the disease’s contemporary persistence despite attempts at eradication.”
“In the wake of COVID-19, animal hosts are now becoming a focus of attention for understanding disease appearance and persistence,” Inskip said. “Our research shows that there is a long history of zoonotic diseases, and they have had and continue to have a big impact on us.”

Published47 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Aurelia FosterHealth reporter, BBC NewsThe fertility regulator has extended the closure of a London clinic, which is under investigation following the “tragic loss” of some embryos.Homerton Fertility Centre had its licence suspended in March after some frozen embryos did not survive being thawed or were “undetectable”. Hundreds of patients had their treatment delayed or put on hold. The regulator said it would not let the clinic reopen until it was certain patients could be treated safely.The Human Fertilisation and Embryology Authority (HFEA) said it took the rare decision to close the clinic in Hackney on 8 March for an initial period of two months, because of the “significant concerns” following “three serious untoward incidents”.The HFEA said:In May 2023, “the correct procedure had not been followed” when freezing some embryosIn October 2023, it was reported that a higher than expected number of frozen embryos had not survived the thawing processIn December 2023, some embryos “were not found” when attempts were made to thaw themThe clinic said that while some investigations are complete, the incident in December is still being looked into.The BBC has asked to see the investigation reports.HFEA chief executive Peter Thompson has said the clinic’s licence should remain suspended until August – longer than initially expected – until all investigations are completed.”Serious incidents in fertility clinics in the UK are rare, but each one is distressing for those patients involved, which is why we take them very seriously,” he said. “The HFEA investigates what clinics do in response to incidents to make sure that everything is done to understand what went wrong and, crucially, to take steps to ensure it does not happen again.”‘Worry and distress’Since 8 March, the clinic has only been able to treat some patients who had already started cycles of IVF. Many other patients have frozen eggs or embryos in storage there and are waiting for treatment.The clinic has been banned from starting any treatment cycles, and has only been allowed to continue treatment which had already begun.Homerton Healthcare NHS Foundation Trust said the incidents had highlighted “problems in some freezing processes” and that investigations are continuing.It confirmed that 32 patients had been affected, but that number was “subject to change as our investigations continue”. In March, the trust told the BBC that as many as 150 embryos may have been affected.Its chief executive Bas Sadiq said: “We want to apologise again for the worry and distress these incidents have caused our patients. “We are focused on continuing our investigations and doing everything we can to learn from and rectify the issues which have caused the loss of embryos in the fertility unit.” The trust said that since the incidents, staff now have to work in pairs, staff competencies have been checked and security has been increased.Metropolitan Police officers visited the clinic on 8 March, after concerns were raised by staff members.However, there is no police investigation at this time.The trust said all patients have received letters and offered free counselling.However, many patients the BBC has spoken to said they had received neither.Homerton Fertility Centre has been under a high level of oversight by the HFEA for several years, because of numerous incidents of “non-compliance” identified during inspections.Patients also had treatment delayed when the clinic temporarily closed in 2022, because of staff shortages.More on this storyFertility clinic licence suspended over concernsPublished9 MarchIVF clinic investigated over possible damaged eggsPublished14 FebruaryHospital’s IVF treatment halted over lack of staffPublished26 April 2022Related Internet LinksFertility Centre – Homerton Healthcare NHS Foundation TrustHFEA- UK fertility regulatorHome – Homerton Healthcare NHS Foundation TrustThe BBC is not responsible for the content of external sites.

Close TranscriptFive surprisingly simple ways to optimise your dietOU ACADEMIC ADVISER, SIMON REA, SENIOR LECTURER IN SPORT AND FITNESS SIMON REA When it comes to what you eat, there’s no shortage of advice. TikTok is overflowing with it… the low-carb diet, raw food, cabbage soup, cucumber bagel diet. And on and on. If you’re confused, it’s no wonder. So here’s… TITLE CARD: Five simple tips (you can trust) for healthy eating OK, this one is a bit of game changer. TEXT ON SCREEN: 1: IT’S NOT JUST WHAT YOU EAT, BUT WHEN If you eat a treat – say a slice of chocolate cake – it’s much better to eat it after a meal, than on its own. ACTOR: Why? It’s all about keeping glucose spikes under control. Whenever you eat carbs, or sweet things, the level of glucose in your blood rises. If it rises very quickly, and sharply, it will be followed by a crash. And that crash makes you feel tired, irritable… and hungry again. But there are ways to keep these spikes under control. Exercising after you eat is one. Eating foods higher in fibre – like vegetables or porridge oats – is another. But the order you eat your food matters too. If you’re having something carb-heavy – like white rice or pasta – eating fat, protein or vegetables before, flattens that glucose curve. A little bit of fish, meat, broccoli, an egg… anything like that would do. That’s because having something in your stomach first, slows down how quickly the carbohydrates reach the small intestine for digestion. And it’s the same for that slice of chocolate cake. TEXT ON SCREEN: 2. CALORIE COUNTING IS NOT VERY USEFUL ACTOR: Why? Well, for a start, it’s notoriously hard to do. Most people underestimate their calorie intake by about 25%. But also because not all calories behave in the same way, once inside your body. Foods in their natural state – like nuts, fruit, vegetables, and fish, or anything that’s not been processed – require more energy from the body to digest them. ACTOR: This is called the thermic effect of food. And means that things like nuts, which are high in calories, can still be a healthy option, as the body uses so much energy digesting them. TEXT ON SCREEN: 3. GIVE YOUR GUT MICROBIOME SOME LOVE In recent years, scientists have begun to understand the importance of what’s known as the gut microbiome. The gut microbiome is everything in the digestive tract. It’s a huge ecosystem that contains trillions of bacteria, fungi, viruses and cells. And it can weigh as much as 2 kilos. Research suggests the make-up of your gut microbiome could have really profound effects on your physical health, and potentially on your mental health too. For a healthy microbiome, and a healthy you, you should aim to eat a wide range of different foods. Seeds, fruit, vegetables, the yoghurt drink kefir and other fermented foods are particularly gut-friendly. TEXT ON SCREEN: 4. LIMIT ULTRA-PROCESSED FOODS (UPFs) In the UK, 57% of the calories we eat come from ultra-processed foods. And this figure is even higher for young children. Ultra-processed foods include, as you might expect, things like pizza, ready meals, biscuits. But also some quite surprising things, which tend to be thought of as healthy – like most supermarket bread, many breakfast cereals, and many milk and meat substitutes. UPF are not labelled. But a good a rule of thumb is to look for ingredients you don’t recognise… things you’d never have in your own kitchen. Like emulsifiers, sweeteners, colourings and preservatives. TEXT ON SCREEN: 5. PERSONALISED NUTRITION COULD BE THE FUTURE Another approach that’s the rise at the moment is that of personalised nutrition. And in 2014, two scientists¬,¬¬ Eran Segal and Eran Elinav, found some really surprising results from an experiment. The blood sugar levels in their sample group varied widely after people ate the same food. ACTIR: The explanation? Well, it could be back to the make-up of our unique gut microbiomes. The dream of personalised nutrition is that people would be able to tailor their food choices to the specific needs of their bodies. But nutritionists are keen to point out that some key messages still apply across the board. So, for a healthy diet, aim for foods which are close to their natural state… ACTOR: An orange instead of orange juice. Brown rice instead of white. Dark chocolate instead of milk chocolate. Aim for a wide variety of foods. Try not to eat too many ingredients you don’t recognise. And remember, you are what you eat. But when you eat matters too.

Thousands of Americans believe they experienced rare but serious side effects. But confirming a link is a difficult task.Soon after their arrival in late December 2020, the Covid-19 vaccines turned the pandemic around and opened a path back to normalcy. They prevented about 14.4 million deaths worldwide, according to one estimate.In a small percentage of people, they also produced side effects.Over the course of more than a year, The New York Times talked to 30 people who said they had been harmed by Covid vaccines. Their symptoms may turn out to be unrelated to the shots. But they — along with more than a dozen experts — felt federal officials are not doing enough to investigate their complaints.All vaccines carry some risk of side effects. More than 270 million Americans received about 677 million doses of the Covid vaccines, and even rare side effects — occurring, say, in just 0.001 percent of patients — might mean thousands of recipients were affected.Indeed, more than 13,000 have submitted claims to a government fund that compensates people for Covid vaccine injuries. So far, however, only a dozen people have been compensated, nearly all of them for a heart problem caused by the vaccines.Here are four takeaways from our investigation.For most people, the benefits of Covid vaccines outweigh any risks.Even the best vaccines and drugs have some side effects. That does not negate their benefits, nor does it suggest that people should stop taking them.The rotavirus vaccine, for example, is an unmitigated success, but it can lead to intussusception — a life-threatening condition in which the intestine folds in on itself — in about 0.02 percent of children who are vaccinated.Some side effects caused by the Covid vaccines may be equally rare. Researchers in Hong Kong analyzed that country’s health records and found that about seven of every million doses of Pfizer-BioNTech vaccine triggered a bout of shingles serious enough to require hospitalization.Other side effects are slightly more common. The Covid vaccines may lead to myocarditis, or inflammation of the heart, in one of every 10,000 adolescent males. (Myocarditis is one of the four serious side effects acknowledged by federal health officials.)Deaths from the vaccines are vanishingly rare, despite claims from some conspiracy theorists that vaccines have led to a spike in mortality rates. More intensive analysis may indicate that in some groups, like young men, the benefit of Covid shots may no longer outweigh the risks. But for the majority of Americans, the vaccines continue to be far safer than contracting Covid itself.Federal surveillance has found some side effects but may miss others.To detect problems with vaccines, federal agencies rely on multiple databases. The largest, the Vaccine Adverse Event Reporting System, is useful for generating hypotheses, but contains unverified accounts of harms. Other databases combine electronic health records and insurance claims.These systems spotted blood-clotting problems associated with the Johnson & Johnson vaccine and a potential risk of stroke after mRNA immunizations, which is still under investigation. But federal researchers trailed Israeli scientists in picking up myocarditis as a problem among young men.The American health care system is fragmented, with medical records stored by multiple companies that do not collaborate. Electronic health records do not all describe symptoms the same way, making comparisons difficult. Insurance claims databases may have no record of shots administered at mass vaccination sites.Federal systems may also miss symptoms that defy easy description or diagnosis. Proving vaccination led to an illness is complicated.Among the hundreds of millions of Americans who were immunized against Covid, there were deaths, heart attacks, strokes, miscarriages and autoimmune illnesses. How to distinguish illnesses caused by the vaccine from those that would have happened anyway?The rarer the condition, the harder it is to answer this question.Merely judging by the timing — the appearance of a particular problem after vaccination — can be misleading. Most famously, childhood vaccines were mistakenly linked to autism because the first noticeable features often coincided with the immunization schedule.Serious side effects may first turn up in animal studies of vaccines. But few such studies were possible given the nation’s desperate timeline in 2020. Clinical trials of the vaccines were intended to test their effectiveness, but they were far from big enough to detect side effects that may occur only in a few people per million doses.Most independent studies of side effects have not been large enough to detect rare events, nor to exclude their possibility; others have looked only for a preset list of symptoms and might have missed the rare outliers.An expert panel convened by the National Academies concluded in April that for most side effects, there was not enough data to accept or reject a link to Covid vaccination.Understanding the full range of side effects may take years.Federal health officials acknowledge four major side effects of Covid vaccines — not including the temporary injection site pain, fever and malaise that may accompany the shots.But in federal databases, thousands of Americans have reported that Covid vaccines caused ringing in the ears, dizziness, brain fog, sharp fluctuations in blood pressure and heart rate, new or relapsed autoimmune conditions, hives, vision problems, kidney disorders, tingling, numbness and a loss of motor skills.Some studies have examined reports of side effects and largely concluded that there was no link. Closer scrutiny may reveal that many, perhaps most, of the other reported side effects are unrelated to immunization. Most of them are also associated with Covid, and may be the result of undiagnosed infections. But without in-depth studies, it is impossible to be sure, experts said.

Within minutes of getting the Johnson & Johnson Covid-19 vaccine, Michelle Zimmerman felt pain racing from her left arm up to her ear and down to her fingertips. Within days, she was unbearably sensitive to light and struggled to remember simple facts.She was 37, with a Ph.D. in neuroscience, and until then could ride her bicycle 20 miles, teach a dance class and give a lecture on artificial intelligence, all in the same day. Now, more than three years later, she lives with her parents. Eventually diagnosed with brain damage, she cannot work, drive or even stand for long periods of time.“When I let myself think about the devastation of what this has done to my life, and how much I’ve lost, sometimes it feels even too hard to comprehend,” said Dr. Zimmerman, who believes her injury is due to a contaminated vaccine batch.The Covid vaccines, a triumph of science and public health, are estimated to have prevented millions of hospitalizations and deaths. Yet even the best vaccines produce rare but serious side effects. And the Covid vaccines have been given to more than 270 million people in the United States, in nearly 677 million doses.Dr. Zimmerman’s account is among the more harrowing, but thousands of Americans believe they suffered serious side effects following Covid vaccination. As of April, just over 13,000 vaccine-injury compensation claims have been filed with the federal government — but to little avail. Only 19 percent have been reviewed. Only 47 of those were deemed eligible for compensation, and only 12 have been paid out, at an average of about $3,600.Some scientists fear that patients with real injuries are being denied help and believe that more needs to be done to clarify the possible risks.“At least long Covid has been somewhat recognized,” said Akiko Iwasaki, an immunologist and vaccine expert at Yale University. But people who say they have post-vaccination injuries are “just completely ignored and dismissed and gaslighted,” she added.Once Michelle Zimmerman, who has a Ph.D. in neuroscience, could ride her bicycle 20 miles, teach a dance class and give a lecture on artificial intelligence, all in the same day.Jovelle Tamayo for The New York TimesIn interviews and email exchanges conducted over several months, federal health officials insisted that serious side effects were extremely rare and that their surveillance efforts were more than sufficient to detect patterns of adverse events.“Hundreds of millions of people in the United States have safely received Covid vaccines under the most intense safety monitoring in U.S. history,” Jeff Nesbit, a spokesman for the Department of Health and Human Services, said in an emailed statement.But in a recent interview, Dr. Janet Woodcock, a longtime leader of the Food and Drug Administration, who retired in February, said she believed that some recipients had experienced uncommon but “serious” and “life-changing” reactions beyond those described by federal agencies. “I feel bad for those people,” said Dr. Woodcock, who became the F.D.A.’s acting commissioner in January 2021 as the vaccines were rolling out. “I believe their suffering should be acknowledged, that they have real problems, and they should be taken seriously.”“I’m disappointed in myself,” she added. “I did a lot of things I feel very good about, but this is one of the few things I feel I just didn’t bring it home.”Federal officials and independent scientists face a number of challenges in identifying potential vaccine side effects.The nation’s fragmented health care system complicates detection of very rare side effects, a process that depends on an analysis of huge amounts of data. That’s a difficult task when a patient may be tested for Covid at Walgreens, get vaccinated at CVS, go to a local clinic for minor ailments and seek care at a hospital for serious conditions. Each place may rely on different health record systems.There is no central repository of vaccine recipients, nor of medical records, and no easy to way to pool these data. Reports to the largest federal database of so-called adverse events can be made by anyone, about anything. It’s not even clear what officials should be looking for.“I mean, you’re not going to find ‘brain fog’ in the medical record or claims data, and so then you’re not going to find” a signal that it may be linked to vaccination, Dr. Woodcock said. If such a side effect is not acknowledged by federal officials, “it’s because it doesn’t have a good research definition,” she added. “It isn’t, like, malevolence on their part.”The government’s understaffed compensation fund has paid so little because it officially recognizes few side effects for Covid vaccines. And vaccine supporters, including federal officials, worry that even a whisper of possible side effects feeds into misinformation spread by a vitriolic anti-vaccine movement.Kristian Thacker for The New York Times‘I’m Not Real’Patients who believe they experienced serious side effects say they have received little support or acknowledgment.Shaun Barcavage, 54, a nurse practitioner in New York City who has worked on clinical trials for H.I.V. and Covid, said that ever since his first Covid shot, merely standing up sent his heart racing — a symptom suggestive of postural orthostatic tachycardia syndrome, a neurological disorder that some studies have linked to both Covid and, much less often, vaccination.He also experienced stinging pain in his eyes, mouth and genitals, which has abated, and tinnitus, which has not.“I can’t get the government to help me,” Mr. Barcavage said of his fruitless pleas to federal agencies and elected representatives. “I am told I’m not real. I’m told I’m rare. I’m told I’m coincidence.”Renee France, 49, a physical therapist in Seattle, developed Bell’s palsy — a form of facial paralysis, usually temporary — and a dramatic rash that neatly bisected her face. Bell’s palsy is a known side effect of other vaccines, and it has been linked to Covid vaccination in some studies. But Ms. France said doctors were dismissive of any connection to the Covid vaccines. The rash, a bout of shingles, debilitated her for three weeks, so Ms. France reported it to federal databases twice.“I thought for sure someone would reach out, but no one ever did,” she said.Similar sentiments were echoed in interviews, conducted over more than a year, with 30 people who said they had been harmed by Covid shots. They described a variety of symptoms following vaccination, some neurological, some autoimmune, some cardiovascular.All said they had been turned away by physicians, told their symptoms were psychosomatic, or labeled anti-vaccine by family and friends — despite the fact that they supported vaccines.Dr. Buddy Creech, 50, who led several Covid vaccine trials at Vanderbilt University, said his tinnitus and racing heart lasted about a week after each shot.Eric Ryan Anderson for The New York TimesRenee France, 48, a physical therapist in Seattle, developed Bell’s palsy — a form of facial paralysis, usually temporary — and a dramatic rash.Jovelle Tamayo for The New York TimesEven leading experts in vaccine science have run up against disbelief and ambivalence.Dr. Gregory Poland, 68, editor in chief of the journal Vaccine, said that a loud whooshing sound in his ears had accompanied every moment since his first shot, but that his entreaties to colleagues at the Centers for Disease Control and Prevention to explore the phenomenon, tinnitus, had led nowhere.He received polite responses to his many emails, but “I just don’t get any sense of movement,” he said.“If they have done studies, those studies should be published,” Dr. Poland added. In despair that he might “never hear silence again,” he has sought solace in meditation and his religious faith. Dr. Buddy Creech, 50, who led several Covid vaccine trials at Vanderbilt University, said his tinnitus and racing heart lasted about a week after each shot. “It’s very similar to what I experienced during acute Covid, back in March of 2020,” Dr. Creech said.Research may ultimately find that most reported side effects are unrelated to the vaccine, he acknowledged. Many can be caused by Covid itself.“Regardless, when our patients experience a side effect that may or may not be related to the vaccine, we owe it to them to investigate that as completely as we can,” Dr. Creech said.Federal health officials say they do not believe that the Covid vaccines caused the illnesses described by patients like Mr. Barcavage, Dr. Zimmerman and Ms. France. The vaccines may cause transient reactions, such as swelling, fatigue and fever, according to the C.D.C., but the agency has documented only four serious but rare side effects.Two are associated with the Johnson & Johnson vaccine, which is no longer available in the United States: Guillain-Barré syndrome, a known side effect of other vaccines, including the flu shot; and a blood-clotting disorder.The C.D.C. also links mRNA vaccines made by Pfizer-BioNTech and Moderna to heart inflammation, or myocarditis, especially in boys and young men. And the agency warns of anaphylaxis, or severe allergic reaction, which can occur after any vaccination.Listening for SignalsAgency scientists are monitoring large databases containing medical information on millions of Americans for patterns that might suggest a hitherto unknown side effect of vaccination, said Dr. Demetre Daskalakis, director of the C.D.C.’s National Center for Immunization and Respiratory Diseases.“We toe the line by reporting the signals that we think are real signals and reporting them as soon as we identify them as signals,” he said. The agency’s systems for monitoring vaccine safety are “pretty close” to ideal, he said.Dr. Zimmerman now lives with her parents, and said she could not work, drive or even stand for long periods of time.Those national surveillance efforts include the Vaccine Adverse Event Reporting System (VAERS). It is the largest database, but also the least reliable: Reports of side effects can be submitted by anyone and are not vetted, so they may be subject to bias or manipulation.The system contains roughly one million reports regarding Covid vaccination, the vast majority for mild events, according to the C.D.C. Federal researchers also comb through databases that combine electronic health records and insurance claims on tens of millions of Americans. The scientists monitor the data for 23 conditions that may occur following Covid vaccination. Officials remain alert to others that may pop up, Dr. Daskalakis said. But there are gaps, some experts noted. The Covid shots administered at mass vaccination sites were not recorded in insurance claims databases, for example, and medical records in the United States are not centralized.“It’s harder to see signals when you have so many people, and things are happening in different parts of the country, and they’re not all collected in the same system,” said Rebecca Chandler, a vaccine safety expert at the Coalition for Epidemic Preparedness Innovations.An expert panel convened by the National Academies concluded in April that for the vast majority of side effects, there was not enough data to accept or reject a link.Asked at a recent congressional hearing whether the nation’s vaccine-safety surveillance was sufficient, Dr. Peter Marks, director of the F.D.A.’s Center for Biologics Evaluation and Research, said, “I do believe we could do better.”Mr. Barcavage’s EKG readings on his phone at home. He was among the first to receive the Pfizer vaccine in 2020, and his symptoms included stinging pain in his eyes, mouth and genitals, which has abated, and tinnitus, which has not.Hannah Yoon for The New York Times“I am told I’m not real. I’m told I’m rare. I’m told I’m coincidence,” Mr. Barcavage said.Hannah Yoon for The New York TimesA Red FlagIn some countries with centralized health care systems, officials have actively sought out reports of serious side effects of Covid vaccines and reached conclusions that U.S. health authorities have not.In Hong Kong, the government analyzed centralized medical records of patients after vaccination and paid people to come forward with problems. The strategy identified “a lot of mild cases that other countries would not otherwise pick up,” said Ian Wong, a researcher at the University of Hong Kong who led the nation’s vaccine safety efforts.That included the finding that in rare instances — about seven per million doses — the Pfizer-BioNTech vaccine triggered a bout of shingles serious enough to require hospitalization. The European Medicines Agency has linked the Pfizer and Moderna vaccines to facial paralysis, tingling sensations and numbness. The E.M.A. also counts tinnitus as a side effect of the Johnson & Johnson vaccine, although the American health agencies do not. There are more than 17,000 reports of tinnitus following Covid vaccination in VAERS. Are the two linked? It’s not clear. As many as one in four adults has some form of tinnitus. Stress, anxiety, grief and aging can lead to the condition, as can infections like Covid itself and the flu.There is no test or scan for tinnitus, and scientists cannot easily study it because the inner ear is tiny, delicate and encased in bone, said Dr. Konstantina Stankovic, an otolaryngologist at Stanford University.Still, an analysis of health records from nearly 2.6 million people in the United States found that about 0.04 percent, or about 1,000, were diagnosed with tinnitus within three weeks of their first mRNA shot. In March, researchers in Australia published a study linking tinnitus and vertigo to the vaccines.The F.D.A. is monitoring reports of tinnitus, but “at this time, the available evidence does not suggest a causal association with the Covid-19 vaccines,” the agency said in a statement.Despite surveillance efforts, U.S. officials were not the first to identify a significant Covid vaccine side effect: myocarditis in young people receiving mRNA vaccines. It was Israeli authorities who first raised the alarm in April 2021. Officials in the United States said at the time that they had not seen a link.On May 22, 2021, news broke that the C.D.C. was investigating a “relatively few” cases of myocarditis. By June 23, the number of myocarditis reports in VAERS had risen to more than 1,200 — a hint that it is important to tell doctors and patients what to look for.Later analyses showed that the risk for myocarditis and pericarditis, a related condition, is highest after a second dose of an mRNA Covid vaccine in adolescent males aged 12 to 17 years.In many people, vaccine-related myocarditis is transient. But some patients continue to experience pain, breathlessness and depression, and some show persistent changes on heart scans. The C.D.C. has said there were no confirmed deaths related to myocarditis, but in fact there have been several accounts of deaths reported post-vaccination.Pervasive MisinformationMaddie McGarvey for The New York TimesThe rise of the anti-vaccine movement has made it difficult for scientists, in and out of government, to candidly address potential side effects, some experts said. Much of the narrative on the purported dangers of Covid vaccines is patently false, or at least exaggerated, cooked up by savvy anti-vaccine campaigns.Questions about Covid vaccine safety are core to Robert F. Kennedy Jr.’s presidential campaign. Citing debunked theories about altered DNA, Florida’s surgeon general has called for a halt to Covid vaccination in the state.“The sheer nature of misinformation, the scale of misinformation, is staggering, and anything will be twisted to make it seem like it’s not just a devastating side effect but proof of a massive cover-up,” said Dr. Joshua Sharfstein, a vice dean at Johns Hopkins University.Among the hundreds of millions of Americans who were immunized for Covid, some number would have had heart attacks or strokes anyway. Some women would have miscarried. How to distinguish those caused by the vaccine from those that are coincidences? The only way to resolve the question is intense research.But the National Institutes of Health is conducting virtually no studies on Covid vaccine safety, several experts noted. William Murphy, a cancer researcher who worked at the N.I.H. for 12 years, has been prodding federal health officials to initiate these studies since 2021.The officials each responded with “that very tired mantra: ‘But the virus is worse,’” Dr. Murphy recalled. “Yes, the virus is worse, but that doesn’t obviate doing research to make sure that there may be other options.”A deeper understanding of possible side effects, and who is at risk for them, could have implications for the design of future vaccines, or may indicate that for some young and healthy people, the benefit of Covid shots may no longer outweigh the risks — as some European countries have determined.Thorough research might also speed assistance to thousands of Americans who say they were injured.Ilka Warshawsky, a 58-year-old pathologist, lost all hearing in her right ear after a Covid booster shot, and had vertigo and mild tinnitus.Daniel Lozada for The New York TimesThe federal government has long run the National Vaccine Injury Compensation Program, designed to compensate people who suffer injuries after vaccination. Established more than three decades ago, the program sets no limit on the amounts awarded to people found to have been harmed.But Covid vaccines are not covered by that fund because Congress has not made them subject to the excise tax that pays for it. Some lawmakers have introduced bills to make the change.Instead, claims regarding Covid vaccines go to the Countermeasures Injury Compensation Program. Intended for public health emergencies, this program has narrow criteria to pay out and sets a limit of $50,000, with stringent standards of proof.It requires applicants to prove within a year of the injury that it was “the direct result” of getting the Covid vaccine, based on “compelling, reliable, valid, medical, and scientific evidence.”The program had only four staff members at the beginning of the pandemic, and now has 35 people evaluating claims. Still, it has reviewed only a fraction of the 13,000 claims filed, and has paid out only a dozen.Ilka Warshawsky, a 58-year-old pathologist, said she lost all hearing in her right ear after a Covid booster shot. But hearing loss is not a recognized side effect of Covid vaccination.The compensation program for Covid vaccines sets a high bar for proof, she said, yet offers little information on how to meet it: “These adverse events can be debilitating and life-altering, and so it’s very upsetting that they’re not acknowledged or addressed.”Dr. Zimmerman, the neuroscientist, submitted her application in October 2021 and provided dozens of supporting medical documents. She received a claim number only in January 2023.In adjudicating her claim for workers’ compensation, Washington State officials accepted that Covid vaccination caused her injury, but she has yet to get a decision from the federal program.One of her therapists recently told her she might never be able to live independently again.“That felt like a devastating blow,” Dr. Zimmerman said. “But I’m trying not to lose hope there will someday be a treatment and a way to cover it.”

A new study from Trinity College Dublin scientists, sheds light on the complexities of achieving optimal vitamin D status across diverse populations. Despite substantial research on the determinants of vitamin D, levels of vitamin D deficiency remain high. The study was recently published in the journal Clinical Nutrition.
Dr Margaret M. Brennan, Research Assistant, Department of Public Health and Primary Care, School of Medicine, Trinity College and first author, said:
“We hope this work can highlight the significant differences in vitamin D levels among different ethnic groups at northern latitudes and contribute to efforts to address the long-standing population health issue of vitamin D deficiency.”
The authors analysed data from half a million participants from the United Kingdom (UK,) and for each person, they calculated the individualized estimate of ambient ultraviolet-B (UVB) level, which is the wavelength of sunlight that induces vitamin D synthesis in the skin.
A comprehensive analysis of key determinants of vitamin D and their interactions revealed novel insights. The first key insight is that ambient UVB emerges as a critical predictor of vitamin D status, even in a place like the UK, which receives relatively little sunlight. The second is that age, sex, body mass index (BMI), cholesterol level, and vitamin D supplementation significantly influence how individuals respond to UVB. For example, as BMI and age increase, the amount of vitamin D produced in response to UVB decreases.
Professor Lina Zgaga, Associate Professor of Epidemiology, Department of Public Health and Primary Care, School of Medicine, Trinity College and the principal investigator, said:
“We believe our findings have significant implications for the development of tailored recommendations for vitamin D supplementation. Our study underscores the need to move away from a one-size-fits-all approach towards personalized strategies for optimizing vitamin D status.”
Rasha Shraim, PhD candidate, Department of Public Health and Primary Care, School of Medicine, Trinity College, and co-principal investigator on this study said:
“Our study also highlights the effect that natural environmental factors, like sunlight, can have on our health. We hope that our approach encourages future researchers and public health bodies to integrate these factors into their health and disease work.”
The authors hope that their manuscript will contribute to the ongoing discourse on vitamin D supplementation guidelines.