Publisher Health

National Institutes of Health scientists studying SARS-CoV-2, the virus that causes COVID-19, have defined in Syrian hamsters how different routes of virus exposure are linked to disease severity. Their study, published in Nature Communications, details the efficiency of airborne transmission between hamsters and examines how the virus replicates and causes disease throughout the respiratory system. Their work also shows that virus transmission via fomites — exposure from contaminated surface contact — is markedly less efficient than airborne transmission but does occur.
Scientists from NIH’s National Institute of Allergy and Infectious Diseases conducted the experiments at Rocky Mountain Laboratories in Hamilton, Montana.
To investigate how different routes of exposure affected disease development, the scientists exposed hamsters to SARS-CoV-2 via both aerosols and fomites. For aerosol exposure, the scientists used equipment that controlled the size of virus-loaded droplets. For fomite exposure, they placed a dish contaminated with SARS-CoV-2 in the animal cages.
The scientists found that aerosol exposure directly deposited SARS-CoV-2 deep into the lungs, whereas fomite exposure resulted in initial virus replication in the nose. Regardless of exposure route, animals had SARS-CoV-2 replicating in the lungs, but lung damage was more severe in aerosol-exposed animals compared to the fomite group.
A second part of the study compared animal-to-animal transmission of the virus through the air and in contaminated cage environments (fomites). Airborne transmission was markedly more efficient compared to fomite transmission, suggesting that airborne droplets are a key SARS-CoV-2 transmission route. An additional experiment, using air flowing from infected to uninfected animals, supported the finding: Reversing the airflow from uninfected to infected animals greatly reduced transmission efficiency.
The findings support public health guidance focused on interventions to reduce indoor airborne transmission of SARS-CoV-2. These efforts include masking, increasing air filtration and social distancing, as well as handwashing and regular surface disinfection, particularly in clinical settings.
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According to a study published today in Gastroenterology by researchers at Virginia Commonwealth University Massey Cancer Center and University of Florida Health, Black, Hispanic, Indigenous and Asian Americans remain conspicuously absent from pancreatic cancer clinical trials aimed at testing the most recent treatment advances for this deadly disease.
Not only does this lack of diversity hurt patients belonging to these minority groups — who already shoulder a disproportionate pancreatic cancer burden — but it hurts science too.
“If we don’t have good diversity in clinical trials, how will we ever know whether we have certain drugs that work better in some populations than others?” said study senior author Jose Trevino, M.D., surgeon-in-chief at VCU Massey Cancer Center, chair of surgical oncology at the VCU School of Medicine and associate professor of surgery. “We could be throwing away a really good treatment option for racial and ethnic minority patients.”
For this study, Trevino and colleagues searched the clinicaltrials.gov database for pancreatic cancer treatment trials conducted in the U.S. between 2005 — 2020. Since demographics aren’t typically reported during recruitment, the researchers focused on trials with results — a total of 207 trials, with 8,429 participants altogether.
These data revealed that over the last 15 years, there has been a steady increase in the proportion of pancreatic cancer trials reporting participants’ race and ethnicity, with a sizeable bump after reporting became federally mandated in 2017. In 2020, all of the trials included in this study reported the race and ethnicity of participants.
Yet, the actual inclusion of racial and ethnic minorities has stayed flat over time, stuck at the same disproportionately low rates for more than a decade.

Prediction models based on clinical characteristics and imaging findings may help reduce the false-positive rate in women with dense breasts who undergo supplemental breast cancer screening with MRI, according to a new study in the journal Radiology.
Women with dense breast tissue have a much higher risk of breast cancer compared to those with average breast density. High breast density also markedly reduces the sensitivity of mammography due to the masking effect of the fibroglandular tissue, meaning that cancers can be hidden within dense breast tissue.
For these reasons, breast MRI is considered a potentially useful supplement to mammography screening in women with dense breast tissue. It is the most sensitive imaging technique for diagnosing breast cancer and can differentiate well between lesions and abnormalities of the breast. Research has confirmed its substantial added value as a screening tool for women at high risk of breast cancer.
However, the high sensitivity that makes MRI an excellent screening tool also means it often detects benign lesions that otherwise would have gone unnoticed. Women who get recalled for additional work-up based on these findings potentially face repeat MRI scans, targeted ultrasound and biopsy. The need for additional investigations may cause anxiety in the patient, increase health care costs or lead to biopsy-related complications.
“The reduction of the false-positive recall rate is an important issue when considering the use of breast MRI as a screening tool,” said study lead author Bianca M. den Dekker, M.D., from the University Medical Center Utrecht in Utrecht, the Netherlands.
In the new study, Dr. den Dekker and colleagues developed prediction models to distinguish true-positive MRI screening from false-positives. To create the models, they combined MRI findings with clinical characteristics like body mass index, family history of breast cancer and use of hormone replacement therapy.
They used data from the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial, which evaluated the effectiveness of screening with mammography plus MRI compared to mammography alone in Dutch breast cancer screening participants aged 50 to 75 years, with extremely dense breasts.
Of the 454 women who had a positive MRI result in a first supplemental MRI screening round, 79 were diagnosed with breast cancer, meaning that 375 women had false-positive MRI examinations. The full prediction model, based on all collected clinical characteristics and MRI findings, could have prevented 45.5% of false-positive recalls and 21.3% of benign biopsies, without missing any cancers. The model solely based on readily available MRI findings and age had a comparable performance and could have prevented 35.5% of false-positive MRI screenings and 13.0% of benign biopsies.
“Our prediction models may identify a substantial number of false-positives after first-round supplemental MRI screenings, reducing false-positive recalls and benign biopsies without missing any cancers,” Dr. den Dekker said. “This brings supplemental screening MRI for women with dense breasts one step closer to implementation.”
The researchers intend to perform validation studies using data from different populations. They also want to study the performance of prediction models in subsequent screening rounds. Dr. den Dekker noted that the false-positive rate in the study group fell from 79.8 per 1,000 screenings in the first round to 26.3 per 1,000 in the second.
“This can be partly explained by the availability of prior MRI examinations, which allows comparison for interval change,” she said. “As incident screening rounds have a much lower false-positive rate, separate models may have to be created.”

As people age, mutations can build up in blood stem cells and their clones in a process known as age-related clonal hematopoiesis, or ARCH. ARCH can be a risk factor for acute myeloid leukemia (AML), a form of blood cancer. New research provides insight into why some with ARCH go on to develop AML and others don’t. These findings, recently published in Nature Communications, have the potential to significantly advance the early detection and treatment of AML by identifying those at high risk of the disease so they can be monitored more closely.
The study, co-led by Dr. Philip Awadalla, Senior Principal Investigator and Director, Computational Biology at the Ontario Institute for Cancer Research (OICR) and Dr. Quaid Morris, Member, Computational and Systems Biology, Memorial Sloan Kettering Cancer Center (MSK) and OICR Associate, shows how the interplay of positive, neutral and negative evolutionary selection acting on mutations in aging blood stem cells can lead to AML in some individuals with ARCH. They did so by illustrating how negative selection, or ‘purifying selection’, present in individuals who did not go on to develop a malignancy, prevents disease-related cells from coming to dominate the cell population. These discoveries allow for the differentiation between those with ARCH who are at increased risk of developing AML and those who are not.
“We have shown that the constellation of evolutionary forces at play within hematopoietic stem cells can be a robust indicator of those who are at increased risk of blood cancers such as AML,” says Awadalla. “Being able to accurately classify patients based on risk can allow for more frequent and intensive screening for those with ARCH mutations with a concerning evolutionary signature.”
The research team computationally generated more than five million blood populations, trained a deep neural network model (a type of machine learning) to recognize different evolutionary dynamics and employed the model to analyze blood samples that had undergone deep genomic sequencing. These samples were from 92 individuals who went on to develop AML, and 385 who did not despite the presence of ARCH. The study is one of the first to use a single system of tools to capture the interaction of the multiple evolutionary forces at play in ARCH.
“The models we developed in this study can significantly increase the value of ARCH as a biomarker for blood malignancies,” says Morris. “Our team is looking forward to continuing to bolster our understanding of ARCH and seeing these advancements help patients.”
The researchers were able to show that these alternative evolutionary models were predictive of AML risk over time. Similarly, these tools were able to identify genes where mutations that are damaging to stem cells can accumulate.
“Our novel application of deep learning tools and population genetic models to genomic sequencing allowed us to classify the evolutionary interactions within a blood sample with a very high degree of accuracy,” says Kimberly Skead, first author and PhD Candidate in the Awadalla and Morris Labs at OICR, the Department of Molecular Genetics at the University of Toronto and the Vector Institute for Artificial Intelligence. “This level of resolution enabled us to understand how both positive and negative selection shape the aging blood system and to establish strong links to individual health outcomes, which bodes well for potential clinical use.”
“In the future, we can anticipate screening blood samples for early detection of disease and blood cancers. With these tools we can more proactively monitor people’s health. Early detection of cancer is critical with respect to prevention and effectiveness of treatment,” adds Awadalla.
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Consuming higher amounts of Vitamin D — mainly from dietary sources — may help protect against developing young-onset colorectal cancer or precancerous colon polyps, according to the first study to show such an association.
The study, recently published online in the journal Gastroenterology, by scientists from Dana-Farber Cancer Institute, the Harvard T.H. Chan School of Public Health, and other institutions, could potentially lead to recommendations for higher vitamin D intake as an inexpensive complement to screening tests as a colorectal cancer prevention strategy for adults younger than age 50.
While the overall incidence of colorectal cancer has been declining, cases have been increasing in younger adults — a worrisome trend that has yet to be explained. The authors of the study, including senior co-authors Kimmie Ng, MD, MPH, of Dana-Farber, and Edward Giovannucci, MD, DSc., of the T.H. Chan School, noted that vitamin D intake from food sources such as fish, mushrooms, eggs, and milk has decreased in the past several decades. There is growing evidence of an association between vitamin D and risk of colorectal cancer mortality. However, prior to the current study, no research has examined whether total vitamin D intake is associated with the risk of young-onset colorectal cancer.
“Vitamin D has known activity against colorectal cancer in laboratory studies. Because vitamin D deficiency has been steadily increasing over the past few years, we wondered whether this could be contributing to the rising rates of colorectal cancer in young individuals,” said Ng, director of the Young-Onset Colorectal Cancer Center at Dana-Farber. “We found that total vitamin D intake of 300 IU per day or more — roughly equivalent to three 8-oz. glasses of milk — was associated with an approximately 50% lower risk of developing young-onset colorectal cancer.”
The results of the study were obtained by calculating the total vitamin D intake — both from dietary sources and supplements — of 94,205 women participating in the Nurses’ Health Study II (NHS II). This study is a prospective cohort study of nurses aged 25 to 42 years that began in 1989. The women are followed every two years by questionnaires on demographics, diet and lifestyle factors, and medical and other health-related information. The researchers focused on a primary endpoint — young-onset colorectal cancer, diagnosed before 50 years of age. They also asked on a follow-up questionnaire whether they had had a colonoscopy or sigmoidoscopy where colorectal polyps (which may be precursors to colorectal cancer) were found.
During the period from 1991 to 2015 the researchers documented 111 cases of young-onset colorectal cancer and 3,317 colorectal polyps. Analysis showed that higher total vitamin D intake was associated with a significantly reduced risk of early-onset colorectal cancer. The same link was found between higher vitamin D intake and risk of colon polyps detected before age 50.
The association was stronger for dietary vitamin D — principally from dairy products — than from vitamin D supplements. The study authors said that finding could be due to chance or to unknown factors that are not yet understood.
Interestingly, the researchers didn’t find a significant association between total vitamin D intake and risk of colorectal cancer diagnosed after age 50. The findings were not able to explain this inconsistency, and the scientists said further research in a larger sample is necessary to determine if the protective effect of vitamin D is actually stronger in young-onset colorectal cancer.
In any case, the investigators concluded that higher total vitamin D intake is associated with decreased risks of young-onset colorectal cancer and precursors (polyps). “Our results further support that vitamin D may be important in younger adults for health and possibly colorectal cancer prevention,” said Ng. “It is critical to understand the risk factors that are associated with young-onset colorectal cancer so that we can make informed recommendations about diet and lifestyle, as well as identify high risk individuals to target for earlier screening.”
The study was funded by grants from the U.S. National Institutes of Health and the Department of Defense; by the American Cancer Society Mentored Research Scholar Grant; and by the Project P Fund.
Ng’s disclosures include research funding from Pharmavite, Revolution Medicines, Janssen, and Evergrande Group; Advisory boards for Array Biopharma, Seattle Genetics, and BiomX; and consulting for X-Biotix Therapeutics.

While gut microbiota play a critical role in the induction of adaptive immune responses to influenza virus infection, the role of nasal bacteria in the induction of virus-specific adaptive immunity is less clear. New research published this week in mBio,an open-access journal of the American Society for Microbiology, explores the role of nasal bacteria and provides clues to developing better intranasal vaccines for flu and COVID-19.
“Our study shows that both integrity and amounts of nasal bacteria may be critical for effective intranasal vaccine,” said study principal investigator Takeshi Ichinohe, Ph.D., an associate professor in the Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, the University of Tokyo, Minato-ku, Tokyo, Japan. “We showed that oral bacteria-combined intranasal vaccine protects from influenza virus and SARS-CoV-2 infection.”
In the new study, to determine the effects of nasal bacteria in the induction of mucosal immune responses to influenza virus infection, Dr. Ichniohe and colleagues treated mice intranasally with an antibiotic cocktail to kill the nasal bacteria before influenza virus infection.
The researchers found that disruption of nasal bacteria by antibiotics before influenza virus infection enhanced the virus-specific antibody responses. “We found that intranasal application of antibiotics (to kill nasal bacteria) could release bacterial pathogen-associated molecular patterns (PAMP), which are bacterial components that stimulate innate immunity that act as mucosal adjuvants for influenza virus-specific antibodies response,” said Dr. Ichniohe.
Innate immunity, which is not specific to a particular pathogen, is the first line of defense against non-self pathogens such as bacteria and virus. The main purpose of the innate immune response is to immediately prevent the spread and movement of foreign pathogens throughout the body. The innate immune responses play an essential role for inducing the pathogen-specific adaptive immune responses. Adjuvants are substances that increase or modulate the immune response to a vaccine and stimulate the innate immune system.
The researchers also found that while the upper respiratory tract contained commensal bacteria, relative amounts of culturable commensal bacteria in nasal mucosal surface were significantly lower than that in the oral cavity. The researchers tested whether intranasal supplementation of cultured oral bacteria enhances antibody responses to intranasally administered vaccine and found that oral bacteria combined with intranasal vaccine increased antibody responses to intranasally administered vaccine.
Dr. Ichniohe said the findings provide clues to developing better intranasal vaccines. “We wish to develop effective intranasal vaccines for influenza and COVID-19 in the near future,” said Dr. Ichniohe.
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In one type of a rare, inherited genetic disorder that affects control of body movement, scientists have found a mutation in an enzyme impairs communication between neurons and what should be the inherent ability to pick up our pace when we need to run, instead of walk, across the street.
The disorder is spinocerebellar ataxia, or SCA, a neurodegenerative condition resulting from different genetic mutations whose debilitating bottom line can include ataxia — loss of control of body movement — and atrophy of the cerebellum, a small part of the brain jam packed with neurons, which coordinates movement and balance, says Dr. Ferenc Deak, neuroscientist at the Medical College of Georgia at Augusta University.
The enzyme is ELOVL4, which produces very long chain fatty acids, and its mutation is known to cause the specific SCA type 34. Animal models with this SCA type have problems with motor control by age two months, and scientists from MCG and the University of Oklahoma Health Sciences Center wanted to know precisely why.
“We found a dramatically diminished synaptic response. The information was to go faster, go faster and they never really got the message,” Deak, co-corresponding author of the study in the journal Molecular Neurobiology, says of these communication connections between neurons. “They were transmitting the signal, but when they had to adjust their synaptic connection to coordinate the different movement, that did not happen in the mutant knock-in rat,” he says of the SCA34 model generated using the gene editing technique CRISPR cas9.
Despite the different gene mutations that are causative in SCA, a common bottom line appears to be altered output of the cerebellum and an impact on Purkinje cells, big brain cells in the cerebellum, which can receive about 100 times the input of usual neurons. The big cells also exclusively inhibit communication, so they shut down signals that would interfere with something like a muscle being activated. Loss of these key cells is clear in many forms of SCA, Deak says.
Much like an air traffic controller at a busy airport, these big brain cells obviously monitor a lot of different input simultaneously, and they are the only neuron sending out messages from that part of the brain.

Massachusetts General Hospital (MGH) researchers have identified for the first time how a highly aggressive form of breast cancer can evade one of the most powerful and effective drugs used to treat it, reporting their findings in Cancer Discovery, a journal of the American Association for Cancer Research. The findings could help improve therapy and ultimately prolong survival for patients with metastatic triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is notoriously difficult to treat because it lacks the receptors or “docking sites” for the hormones estrogen and progesterone and the growth factor HER2, all three of which can be targeted with effective cancer therapies. Standard chemotherapy regimens provide limited benefit against TNBC, and patients with metastatic disease — disease that has spread to other parts of the body — have a very poor prognosis and short survival.
But as Aditya Bardia, MD, MPH, from the Mass General Cancer Center and colleagues previously reported, patients with metastatic TNBC treated in a large clinical trial with the compound sacituzumab govitecan (SG; tradename Trovdely) lived nearly twice as long as patients treated with chemotherapy alone.
SG is an antibody-drug conjugate, consisting of an antibody targeted to a receptor called Trop2 found on the surface of most breast cancer cells, plus a cancer-killing compound known as SN-38 (topoisomerase I inhibitor). SG is designed to specifically seek out breast cancer cells and deliver SN-38 as its toxic “payload.”
Yet some patients with metastatic TNBC either do not benefit from treatment with SG or have an initial response to treatment but then develop drug-resistant disease.
Now, Bardia, with Leif Ellisen MD, PhD, director of Breast Medical Oncology at Mass General Cancer Center, and MGH colleagues, report that they have identified for the first time two separate alterations in the genome of TNBC cells that allow them to develop resistance to the antibody-drug conjugate in patients with triple-negative breast cancer.
“We undertook a study to look at the mechanisms of acquired resistance,” says Ellisen.
“In terms of de novo resistance, the data supported prior studies which suggested that the complete absence of Trop2 could be an important predictor of primary resistance. But the really remarkable part of the study had to do with acquired resistance,” he says.
When they studied the genomic profiles of tissues sampled both before treatment and after disease progression, they found that in multiple metastatic lesions from one woman who had an initial robust response to SG but later had disease progression and died from the disease, there were different molecular mechanisms of resistance in different metastatic lesions.
“All of the resistance mechanisms were driven by genetic changes in the metastatic tumor cells that were not present in the primary tumor. Remarkably, in one set of metastatic lesions there was a mutation in the Trop2 target of the antibody, and in another set of lesions there was actually a mutation in the target of the cytotoxic [cell-killing] payload,” says Ellisen.
“This is the first report describing mechanisms of acquired resistance to sacituzumab govitecan,” adds Bardia. “The findings have potential clinical significance for guiding antibody-drug conjugate sequencing for patients with breast cancer.”
The study was supported by grants from the National Institutes of Health, the DoD Breast Cancer Research Program, the Terri Brodeur Breast Cancer Foundation Fellowship, MGH ECOR Fund for Medical Discovery Fellowship, Susan Eid Tumor Heterogeneity Initiative, Tracey Davis Breast Cancer Research Fund and by the Broad/IBM Cancer Resistance Research Project.
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A policy has not been set. But nursing home residents and health care workers would most likely be first in line.WASHINGTON — With a stockpile of at least 100 million doses at the ready, Biden administration officials are developing a plan to start offering coronavirus booster shots to some Americans as early as this fall even as researchers continue to hotly debate whether extra shots are needed, according to people familiar with the effort.The first boosters are likely to go to nursing home residents and health care workers, followed by other older people who were near the front of the line when vaccinations began late last year. Officials envision giving people the same vaccine they originally received. They have discussed starting the effort in October but have not settled on a timetable.While many outside experts argue there is no proof yet that the vaccines’ protection against severe disease and hospitalization is waning in the United States, administration officials say they cannot afford to put off figuring out the logistics of providing boosters to millions of people until that tipping point is reached. The spotty nature of the nation’s disease-reporting network makes the question of timing even trickier.The effort comes as yet another wave of the coronavirus grips the nation, reversing much of the progress the administration had made. Hospitals in states like Texas, Louisiana and Mississippi are again swamped with patients, the vast majority of them unvaccinated.Among other indicators, officials say, the administration is carefully watching Israel, where some data suggests an uptick in severe disease among older adults who received the Pfizer-BioNTech vaccine early in that nation’s campaign, according to people who have reviewed it. Some officials are concerned that even if a decline in protection merely results in mild or asymptomatic infections, those infected people could still spread the virus and prolong the pandemic.Any booster policy decision is fraught, officials said, because the administration does not want to undermine public confidence in what have proved to be powerfully effective vaccines. Nor does it want to overvaccinate Americans when many other countries have yet to even begin vaccination campaigns in earnest, increasing the threat of dangerous new variants that could spread to the United States and evade the vaccines.The World Health Organization has called for a moratorium on booster shots until the end of September, saying available doses should be used to help countries that are far behind in vaccinations.Regulators for the European Union said this month that there was not yet enough data to justify boosters. Germany and France nevertheless have announced plans to start giving booster shots to the older adults and other vulnerable populations next month.Israel, which is already administering booster shots to people over 60, announced on Thursday that it would offer them to those over 50 as well. Britain so far is holding off, but already has a detailed plan for distributing boosters to people 50 and over.More than a million Americans have already managed to get booster shots, even though the Food and Drug Administration has not even been asked to rule on whether they are safe or effective.They represent fewer than 1 percent of those who have been fully vaccinated. But more people could try to follow suit once regulators fully approve the Pfizer-BioNTech vaccine, a move that is expected by early next month. Even though the regimen calls for two shots, doctors would be able to prescribe a third for patients at that point without fear of violating F.D.A. rules.Late this week, the F.D.A. authorized third doses of the Pfizer and Moderna vaccines for certain people with weakened immune systems and the C.D.C. recommended them. The authorities decided those individuals, who make up fewer than 3 percent of Americans, merited extra shots because many fail to respond to the standard dosage.Administration officials continued to insist that boosters remained unnecessary for the general population for now. Determining at what point that changes is difficult because administration experts lack up-to-date data on so-called breakthrough infections in vaccinated people, including their prevalence, when such people were vaccinated and which vaccine they received.Instead, officials are analyzing a complex array of information from a range of sources, including from the vaccine manufacturers Moderna and Pfizer-BioNTech, which has an agreement with the Israeli government to review its data. Other sources of information include a variety of foreign governments, and the Centers for Disease Control and Prevention, which collects data from states and hospitals. All of that data is subject to interpretation and can be marshaled to support arguments for or against boosters.“It’s somewhat chaotic, with everybody doing their own thing,” said Dr. Jesse L. Goodman, a former chief scientist at the F.D.A. and now a medical professor at Georgetown University. “We need a system to monitor real-world vaccine effectiveness in near-real-world time.”He added: “When something comes up like the Pfizer report on Israel, we should be able to say, ‘Are we seeing that here?’ I’m very distressed that we’re not there yet.”Some federal officials cast the booster discussions as contingency planning; others suggested boosters for the general population were extremely likely and the questions were how to give it to them and when.Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases and a key White House adviser, said on Thursday that officials were busy planning because “sooner or later you will need a booster.”Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases and a key White House adviser, said that boosters were inevitable.Stefani Reynolds for The New York TimesJeff Zients, the White House coronavirus coordinator, said that if and when extra shots were needed, they would be rolled out “in a fast and efficient way.”Vaccine makers, who run multibillion-dollar businesses, have been among the most vocal proponents of boosters.“Countries will have to decide either to be two months too early or two months too late,” Stéphane Bancel, the chief executive of Moderna, said in an interview on Monday. While the decision is up to public health authorities, he said, “Our recommendation would be to be two months too early because we can save lives and prevent hospitalization.”On the other side are some influential scientists who say booster shots are at best premature and at worst unethical absent convincing real-world evidence showing that the effectiveness of the vaccines against severe disease and hospitalization is waning.“Vaccinate the unvaccinated, vaccinate the world, and then talk about boosters,” said Dr. Luciana L. Borio, a former acting chief scientist at the Food and Drug Administration.According to the C.D.C., only a tiny fraction of the more than 166 million fully vaccinated Americans have been hospitalized for Covid-19 or have died. Of that number — 8,054 as of Aug. 9 — three-fourths were 65 or older. But the agency says the true total is likely larger because the data relies on voluntary reporting from the states.Data from Israel has prompted growing concern. With only 8.7 million residents, Israel has outpaced the United States in vaccinating its population. It has relied almost exclusively on the Pfizer-BioNTech vaccine and has a nationalized health care system that allows it to systematically track patients.Researchers at Israel’s Ministry of Health have said that the Pfizer vaccine’s effectiveness in preventing infection fell from 95 percent early in the year to 39 percent from late June to mid-July. The vaccine’s overall efficacy against severe disease remained high, though, at 91.4 percent.More recent Israeli data suggests continued erosion. One person who has reviewed it said it showed that the Pfizer vaccine’s efficacy against severe disease had dropped significantly for those 65 and older who got their first shots in January or February.Nurses caring for a Covid-19 patient in Santa Monica, Calif. Some hospitals are finding themselves swamped with such patients, the majority of them unvaccinated.Isadora Kosofsky for The New York TimesModerna officials reported in an earnings call last week that six months after a person received their second dose, the strength of their antibodies against variants was found to have waned substantially. But many scientists say that waning antibodies are expected and should not be viewed as a sign that a vaccine is working less well.In general, U.S. scientists are frustrated with how bits and pieces of often conflicting data are dribbling out in company news releases and studies that have not been peer-reviewed or published in scientific journals.The C.D.C. has said it is following breakthrough infections in specific population segments, including health care workers, emergency medical workers and nursing home residents. But the reports posted on its website rely on data from months ago, before the Delta variant became dominant.“Everyone is confused because there is not a lot of published data,” Dr. Peter J. Hotez, a vaccine expert with the Baylor College of Medicine in Houston, said. “The question is how vulnerable are we, and the numbers are a bit all over the map.”While some federal officials have argued that any booster should be tailored to the Delta variant, the administration is expected to use the same vaccines that have already been manufactured and that studies indicate work well against the Delta variant.Mr. Bancel, Moderna’s chief executive, said his company would not have a vaccine targeted specifically to the Delta variant until the end of the year. Pfizer is on a similar track.Both companies are expected to apply soon to the F.D.A. for authorization of a third shot of their existing two-dose vaccines. Moderna is studying the effectiveness of both a full dose and half dose as a booster.N.I.H. researchers are conducting trials to determine if giving people a booster shot of a different vaccine from the one they originally received provides better protection. While a mix-and-match effort could be hard to organize, officials want to see that data.“It’s a little compressed from what you would normally want,” said Dr. John Beigel, who is leading the study. “But we want to make sure we have data to inform decisions this fall.”Benjamin Mueller

PALB2 is not as well known as BRCA, but mutations of the gene can raise a woman’s risk for breast cancer almost as much.For years, women with breast cancer in their families have been getting tested for mutations in two genes, known as BRCA1 and BRCA2, to determine whether they have a sharply elevated risk of the disease.Now, doctors are increasingly recommending that anyone who was tested before 2014 go through genetic testing again — to look for a different mutation, one much less widely known.It’s on a gene called PALB2, and people who have the mutation have almost as great a risk of getting breast cancer as those who have the BRCA mutations. Like the BRCA mutations, this mutation also increases a patient’s risk of ovarian and pancreatic cancer.Anyone who gets a genetic test for breast cancer now will likely be screened for PALB2 mutations, which were found in 2014 to significantly raise breast cancer risk. But many patients screened before 2014 were not tested for it and may have a false sense of security if they were found to be free of the BRCA mutations, breast cancer experts said.Even now, few patients have heard of the gene, while BRCA is familiar to many.“Hereditary breast cancer risk assessment needs to go beyond BRCA1 and BRCA2 and include genes like PALB2,” said Dr. Peter Hulick, medical director of the Mark R. Neaman Center for Personalized Medicine at NorthShore University HealthSystem in Evanston, Ill. “Raising awareness with physicians and patients is critical, otherwise patients are getting an incomplete genetic assessment.”This spring, a major association of medical geneticists issued new guidance for patients and doctors advising that women with PALB2 mutations be surveilled similarly to patients with BRCA mutations, and that, depending on family history, mastectomies could be an option to reduce the risk in some patients.The guidance, issued by the American College of Medical Genetics and Genomics, called the PALB2 mutation the “third most important breast cancer gene after BRCA1 and BRCA2.” Guidelines from National Comprehensive Cancer Network, as well as from the medical genetics organization, suggest women with the PALB2 mutation should have breast M.R.I.s and mammograms, alternating every six months. The guidance was based on peer-reviewed evidence by a global team of experts in cancer genetics.Dr. Hulick said the risk of developing breast cancer was 40 percent to 60 percent greater among women with the PALB2 mutation, similar to the risk from BRCA.“The reality is we are all at risk for something, it’s just whether we have that line of sight. It’s a real awareness issue,” Dr. Hulick said. “Now people can put PALB2 in their care plan along with structured family history tools.Susan Karnick of Crystal Lake, Ill., opted for a prophylactic mastectomy when she tested positive for the gene. After surgery, it was found she had stage one breast cancer in one breast and five precancerous lesions in the other, despite routine scans.Taylor Glascock for The New York TimesSusan Karnick’s mother had breast cancer years ago, and genetic testing showed no BRCA mutation. Ms. Karnick, 55, of Crystal Lake, Ill., had breast calcification and was alternating mammograms and M.R.I.s every six months when her doctor suggested genetic testing. It showed she had PALB2.After consulting with a high-risk oncologist, she opted for a prophylactic mastectomy. After the surgery, pathology showed she had stage one breast cancer in one breast and five precancerous lesions in the other, in spite of the surveillance every six months.“My doctor said he was happy I didn’t even wait a month or two,” Ms. Karnick said. “I needed no chemo or radiation.”She is enrolled in a pancreatic cancer prevention program at the University of Wisconsin and will undergo screening. Because she had previously had a hysterectomy to treat benign ovarian cysts, ovarian cancer is not a concern.“I was just so grateful for that genetic testing,” she said. “It was stressful and scary but my goodness, I had lifesaving surgery and I would not have known.”Douglas R. Stewart, a co-author of the new guidance, said that PALB2 is sometimes referred to as “BRCA3, given its importance in risk of breast cancer.” He added that those with the mutation “face challenging questions, especially about their personal risk to develop cancers of the breast, ovaries and pancreas, and how to manage that risk.”Everett Lally, a genetic counselor at Seattle Cancer Care Center said it is not only family history but there are psychological considerations as well. He said the women with a first degree relative with breast cancer will likely find it easier to decide on a bilateral mastectomy than a woman with PALB2 mutation and no history of breast cancer.The BRCA mutation received wide publicity in 2013 when the actress Angelina Jolie underwent a prophylactic mastectomy upon learning she had it. Her mother had breast cancer and died at age 56 of ovarian cancer.Historically, when genetic testing was more expensive, specific target testing was done. Today, Dr. Hulick said, testing is much cheaper, and for women with an indication of breast cancer, broad screening panels, which include PALB2 and other cancer genes, are often done. But he noted that genetic testing in general does not yet reach enough women.Over the course of their lives, women have about a 12 percent chance of developing breast cancer and a 1.2 percent chance of developing ovarian cancer, according to the National Cancer Institute.Unlike BRCA1 and BRCA2, which are often found in the Ashkenazi Jewish population, PALB2 is not associated with the Ashkenazi group. Some studies have found a PALB2 association with Finish and French Canadian and Greek women, but experts say more research is needed.The new guidelines for the PALB2 mutation, particularly for those who have pancreatic cancer in their families, now suggest pancreatic screening, which involves having M.R.I.s of the pancreas as well as an endoscopic ultrasound. The new guidelines not only improve care, but a recent study in Journal of Gastrointestinal Surgery shows early detection improves outcomes, which encourages insurance to cover screening.Ms. Marsh keeps a genealogy chart to track the mutation for Dr. Marc Tischkowitz, a geneticist at the University of Cambridge and creator of the PALB2 Interest Group, who is conducting a study on the mutation.Jovelle Tamayo for The New York TimesHeidi Marsh, 46, of Seattle, tested positive for the PALB2 mutation after her mother — a breast cancer and pancreatic cancer patient — was found to have it. She said her own doctor was unaware of the gene.“My OB-GYN was aware of my mom’s history and never suggested genetic testing,” Ms. Marsh said. “She never heard of it. I educated her. The oncologist she sent me to did not suggest surgery.”But Seattle Cancer Care Alliance, a partner of Fred Hutchinson Cancer Research Center, where Ms. Marsh’s mother had been an oncology nurse, did know about the gene mutation. The group immediately put together a team that included a surgical oncologist, a pancreatic cancer specialist, a geneticist, a nutritionist and a social worker.“This has been life-changing,” said Ms. Marsh, who had her fallopian tubes removed in April. (She was told most ovarian cancer first occurs in the tubes. She plans to remove her ovaries after menopause.)She will have breast monitoring with alternating mammograms and breast M.R.I.s every six months. She has already had an endoscopic ultrasound to look at her pancreas.She has found a Facebook group, PALB2 Warriors, to be helpful. Because she has a background in health care — she was a phlebotomist — she says she looks further than individual postings, to studies that are placebo-controlled and peer-reviewed for information. But when it comes to personal stories of experience with prophylactic mastectomies and reconstruction, she says that is invaluable.“This was not remotely on my radar screen,” she said. “In one sense I feel empowered. But I also feel like I am waiting for the other shoe to drop, that cancer will be inevitable.”But mostly, she is thankful that she knows about PALB2 and the risks involved.“It’s an alarm clock and a wake-up call,” she said. “You can do something about it if you choose.”