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Just after 1 p.m. on Tuesday last week, my phone buzzed with a text message from my mother: “Well, came down with cold, aches, cough etc over wknd.” She had taken an at-home coronavirus test. It was positive.Having spent the past year writing about Covid-19 vaccines and treatments for The New York Times, I knew a lot about the options available to people like my mother. Yet I was about to go on a seven-hour odyssey that would show me there was a lot I didn’t grasp.My mother, Mary Ann Neilsen, is fully vaccinated, including a booster shot, which sharply reduced the odds that she would become seriously ill from the virus. But she has several risk factors that worried me. She’s 73. She has twice beaten breast cancer.Her age and cancer history made her eligible to receive the latest treatments that have been shown to stave off the worst outcomes from Covid. The trouble, as I knew from my reporting, was that these treatments — including monoclonal antibody infusions and antiviral pills — are hard to come by.Demand for the drugs is surging as the Omicron variant of the coronavirus infects record numbers of Americans. But supplies are scarce. The two most widely used antibody brands don’t appear to work against Omicron, and the antiviral pills are so new and were developed so quickly that not many have reached hospitals and pharmacies.I set out to track down one of two treatments: GlaxoSmithKline’s antibody infusion or Pfizer’s antiviral pills, known as Paxlovid. Both have been found to be safe and highly protective against severe Covid when given to high-risk patients within a few days of the onset of symptoms. Both are potent against Omicron.One of my first steps was to search online for lists of pharmacies and clinics near my mother’s home in Santa Barbara, Calif., that might have one of the drugs in stock. (I live in Washington State, so my quest was conducted, like so much else these days, remotely.)Some states, like Tennessee and Florida, have useful online tools for finding a facility with monoclonal antibodies in stock. But I couldn’t find one for California. I checked a federal database, which had only one listing within 25 miles of my mother.When I called that health system, I was told that it had run out.I also hunted for Paxlovid. From my reporting, I knew about a federal database of pharmacy chains, hospital systems and other providers that have placed orders for the pills. A Times colleague downloaded the data, as anyone can do, and sent it to me in a more easily searchable format.The list turned up only a few possibilities, mostly pharmacies, near my mother. I dialed the closest one, a CVS, but an employee informed me that the store had quickly run out of the first shipment of pills and didn’t know when more would come.After a few more calls, I found a Rite Aid, more than an hour’s drive from my mother’s apartment, that had Paxlovid in stock. The pharmacy warned me that the supply was going fast.Still, this was good news. I figured I had just surmounted the toughest obstacle, and only two hours had passed since my mother tested positive. Now I just needed to get her a prescription.Ms. Neilsen at her home in Santa Barbara, Calif.Alex Welsh for The New York TimesI had already asked my mother to call her doctor’s office and request a phone call with her physician so she could ask for a prescription for one of the treatments. She reported back to me that the receptionist had told her that they “don’t do” either the Glaxo or Pfizer treatments.That didn’t make sense to me: The Food and Drug Administration has authorized the drugs. Why wouldn’t doctors be prescribing them? Frustrated, I called her doctor’s office to get an explanation. (I did not identify myself as a Times reporter, in that phone call or the others I made that day, in part because I did not want to create the appearance of seeking preferential treatment.)The employee who answered the phone told me that the doctors there had yet to conduct their own medical review of Paxlovid and, as a matter of policy, could not yet prescribe it. Moreover, the employee told me, my mother would need an appointment to speak to a doctor, and there were no slots until a week later.I began hunting for another doctor who would promptly write a prescription.I tried scheduling visits with several telemedicine providers, including CVS and Teladoc, but I kept seeing a similarly worded notification on the intake forms: They were not writing prescriptions for Paxlovid or molnupiravir, a similar antiviral pill from Merck.(Later, I asked both companies about these policies. A CVS spokeswoman said providers were prescribing the antiviral pills to patients they saw in person at some stores but not via telemedicine. A Teladoc spokesman said the company believed at this point that “it’s most appropriate” for the antiviral pills to be prescribed in person.)I started calling urgent care clinics and health systems near my mother to see if they would write her a prescription. At one point, we even got her on a video call with a doctor at a nearby health system.The Coronavirus Pandemic: Key Things to KnowCard 1 of 4Omicron in retreat.

The level of magnesium in the blood is an important factor in the immune system’s ability to tackle pathogens and cancer cells. Writing in the journal Cell, researchers from the University of Basel and University Hospital Basel have reported that T cells need a sufficient quantity of magnesium in order to operate efficiently. Their findings may have important implications for cancer patients.
Magnesium deficiency is associated with a variety of diseases, such as infections and cancer. Previous studies have shown that cancerous growths spread faster in the bodies of mice when the animals received a low-magnesium diet — and that their defense against flu viruses was also impaired. However, there has so far been little research into how exactly this mineral affects the immune system.
Now, researchers led by Professor Christoph Hess, from the Department of Biomedicine at the University of Basel and University Hospital Basel and the Department of Medicine at the University of Cambridge, have discovered that T cells can eliminate abnormal or infected cells efficiently only in a magnesium-rich environment. Specifically, magnesium is important for the function of a T cell surface protein called LFA-1.
LFA-1 acts as a docking site, which plays a key role in the activation of T cells. “However, in the inactive state this docking site is in a bent conformation and thus cannot efficiently bind to infected or abnormal cells,” Christoph Hess explains. “This is where magnesium comes into play. If magnesium is present in sufficient quantities in the vicinity of the T cells, it binds to LFA-1 and ensures that it remains in an extended — and therefore active — position.”
Potentially important findings for cancer patients
The fact that magnesium is essential for the functioning of T cells may be a highly significant finding for modern cancer immunotherapies. These therapies aim to mobilize the immune system — in particular cytotoxic T cells — to fight cancer cells. In experimental models, the researchers were able to show that the immune response of T cells against cancer cells was strengthened by an increase in the local magnesium concentration in tumors.
“In order to verify this observation clinically, we’re now looking for ways to increase the concentration of magnesium in tumors in a targeted manner,” Christoph Hess says. The promising nature of these strategies is demonstrated by further analyses performed by the research team working with Christoph Hess and his Postdoc, Dr. Jonas Lötscher, lead author of the study. Using data from previously completed studies of cancer patients, the researchers were able to show that immunotherapies were less effective in patients with insufficient levels of magnesium in their blood.
Whether a regular intake of magnesium impacts the risk for developing cancer is a question that cannot be answered based on the existing data, says Lötscher. “As a next step, we’re planning prospective studies to test the clinical effect of magnesium as a catalyst for the immune system.”
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It took a global pandemic, but the critical role of messenger RNA in all of life’s functions has taken center stage in the past year with the successful rollout of mRNA vaccines to combat the SARS-Cov-2 virus.
In two new papers published the week of Jan. 17, the lab of Yale’s Wendy Gilbert sheds light on how mRNAs are born and how they regulate production of proteins inside of our cells once they reach maturity. The findings have implications not only for achieving effective doses for new vaccines, but for helping determine the biological roots of many cancers and diseases.
“It’s been exciting to be able to study the beginning and end of this process,” said Gilbert, associate professor of molecular biophysics and biochemistry.
In classic textbook biology, cells precisely copy or transcribe genes encoded in DNA into mRNAs, which then ferry those instructions to the ribosome, the machinery within the cell that makes the proteins that carry out almost all life functions. This key role played by mRNA has made the molecule a major research target for decades, including research that led to the rapid development of mRNA vaccines in the fight against COVID-19. The vaccines developed by Pfizer and Moderna contain mRNA-based instructions for cells to produce proteins that recognize spike proteins on the surface of the SARS-Cov-2 virus, making them targets for destruction by the immune system.
While RNA is formed from just four bases, or nucleotides, its structure and function can be altered by complex biochemical interactions with other compounds. One such compound that modifies mRNA is pseudouridine, an isomer whose presence is a key to the effectiveness of mRNA vaccines. Even before the pandemic, Gilbert’s lab discovered the presence of pseudouridine in normal cellular mRNA. At the time, she became curious about how exactly these mRNA modifications are created and how they affect the mRNA’s function.
In one of the new studies, a team led by Nicole Martinez, a postdoctoral fellow in Gilbert’s lab, found that pseudouridine plays a key role in the genesis of mRNAs. The team found pseudouridine present at the earliest stages of the formation of mRNAs. And the researchers discovered evidence that it guides the splicing of genetic material that creates mRNAs, which in turn regulate gene activity, they report Jan. 19 in the journal Molecular Cell.
These findings shed new light on origins of diseases linked to variants of pseudouridine such as mitochondrial myopathy, digestive disorders, intellectual disability, and resistance to viral infection. For instance, several cancers have been linked to elevated levels of pseudouridine, suggesting that faulty splicing of mRNAs may trigger tumor formation and cancer metastasis.
In a second paper, published Jan. 17 in the journal Cell Systems, Yale researchers investigated just how it is that ribosomes know how many proteins to produce from the genetic instructions they receive from mRNAs. For the study, a team headed by Rachel Niederer, an associate research scientist in Gilbert’s lab, developed new technology called direct analysis of ribosome targeting (DART) to find regulatory elements that can spur and silence the production of proteins by ribosomes. Manipulating such elements in mRNAs — in this case, within yeast — allowed scientists to modify production of proteins by a thousand-fold, they report.
The ability to precisely manipulate protein production has immediate applications in adjusting doses in mRNA vaccines such as those used to combat COVID, the researchers say. Their work led to a $1.7 million grant from Pfizer to the Gilbert lab and that of Carson Thoreen, associate professor of cellular and molecular physiology at Yale.
Gilbert stressed, however, that the technology could also be applied to development of any protein-based therapies for a multitude of diseases.
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Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

Children in sub-Saharan Africa who are hospitalized with COVID-19 are dying at a rate far greater than children in the U.S. and Europe, according to a new multicenter study published today in JAMA Pediatrics and led by a University of Pittsburgh infectious diseases epidemiologist.
Among African children admitted to 25 hospitals with COVID-19 between March and December 2020, infants younger than 1 year had nearly five times the risk of death than adolescents aged 15 to 19 years. Children of all ages with comorbidities, including high blood pressure, chronic lung diseases, hematological disorders and cancer, also were at higher risk of dying.
“Although our study looked at data from earlier in the pandemic, the situation hasn’t changed much for the children of Africa — if anything, it is expected to be worsening with the global emergence of the highly contagious Omicron variant,” said lead author Jean B. Nachega, M.D., Ph.D., M.P.H., associate professor of infectious diseases and microbiology and epidemiology at Pitt’s Graduate School of Public Health. “Vaccines are not yet widely available, and pediatric intensive care is not easily accessible.”
The study examined outcomes in 469 children who ranged in age from 3 months to 19 years and were hospitalized in one of six countries: the Democratic Republic of the Congo, Ghana, Kenya, Nigeria, South Africa and Uganda. A quarter of the children had pre-existing conditions. Eighteen had confirmed or suspected multisystem inflammatory syndrome, a serious complication of COVID-19 where different parts of the body become inflamed.
The study, which included investigators across all six of the African countries that provided data, found that 34.6% of hospitalized children were admitted to an intensive care unit (ICU) or required supplemental oxygen, and 21.2% of those admitted to the ICU required invasive mechanical ventilation. During the time frame studied, 39 — over 8% — of the children died. This compares with rates between 1% and 5% that have been reported in high-income countries.
“The high morbidity and mortality associated with hospitalized children with COVID-19 in our study challenge the existing understanding of COVID-19 as a mild disease in this population,” said Nachega, also a professor extraordinary of medicine at Stellenbosch University’s Faculty of Medicine and Health Sciences in Cape Town, South Africa. “But if a child has a comorbidity, is very young and is in a place where there are limited or no specialized doctors, facilities or equipment for pediatric intensive care, then that child faces a very real possibility of dying.”
“Our findings call for an urgent scale-up of COVID-19 vaccination and therapeutic interventions among at-risk eligible children and adolescents in Africa,” Nachega continued. “They also raise further the acute need for capacity-building and support for pediatric intensive care in these settings.”
Nachega noted recent progress on increasing the COVID-19 vaccine supply in Africa but emphasized that those vaccines are not yet widely available and only about 5% of the continent’s population has been fully vaccinated.
“COVID-19 vaccine hesitancy is a global issue, and Africa is no exception,” he said. “It is imperative that evidence-based public health campaigns address concerns in accessible, trustworthy ways so that there is high vaccine uptake as soon as it is available.”
Additional investigators of this study are members of the African Forum for Research and Education in Health COVID-19 Research Collaboration on Children and Adolescents and are listed in the JAMA Pediatrics article.
This research was supported by National Institutes of Health Fogarty International Center grant 1R25TW011217-01.
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New research by a team led by researchers from the Department of Cardiovascular Medicine at Tokyo Medical and Dental University (TMDU); and the Department of Cardiovascular Medicine at Tokyo Kyosai Hospital has opened up interesting pathway towards the attenuation of atherosclerosis, potentially giving a brighter future to many millions of sufferers of this often fatal disease.
Atherosclerosis is a chronic disease and is one of the major causes of death worldwide. The current situation as regards treatment for this disease is mainly based on drug therapy, however, the maximum efficacy of these therapies for inhibiting the progression of the disease remains at only 30%-40%.
For some time now there has been increasing evidence that a direct oral factor Xa inhibitor plays a large role in the attenuation of atherosclerosis by the suppression of protease-activated receptor 2, which we shall call PAR2. The problem to this point however, has been in coming to an understanding of the precise mechanism by which the promotion of this atherogenesis occurs.
New research by the team now shows that the administration of Rivaroxaban (RIV) in a sufficient dosage can enable the suppression of activity by the factor Xa, and effectively attenuates the atherosclerotic areas in mice. RIV is widely used as a potent anticoagulant agent for preventing cerebral embolism in patients with atrial fibrillation and pulmonary thromboembolism. Studies have demonstrated that it can be greatly effective in reducing the risk of death from coronary artery diseases and that it can also play a significant role in suppressing the progression of atherosclerosis.
In the present study, the focus was on exploring the detailed mechanism whereby RIV attenuates atherosclerosis progression and thus aids in the stability of advanced atherosclerotic lesions in mice.
Several previous preclinical studies had clearly demonstrated that RIV alleviated the progression of atherosclerotic lesions and promoted plaque stability in mice, however, details with regard to the mechanism by which RIV negatively regulates the progression of atherosclerotic lesions and plaque instability still remain unknown.
Observations made in these previous studies led the team to hypothesize that factor Xa-mediated PAR2 activation and thus played a critical role in the progression of atherosclerosis, partially through the downregulation of the autophagy machinery. The new research shows clearly that RIV actually attenuates atherogenesis by inhibiting the factor Xa-PAR2-mediated suppression of macrophage autophagy, and thus abrogates inflammasome activity.
Though previous studies supported the anti-atherosclerotic effects of RIV, there were a lot of divergence in results. It was therefore postulated that the possibly small dosage of RIV administered was not sufficient. To solve this problem, the optimal dosage of RIV to effectively suppress Factor Xa activities in mice was determined.
The US Food and Drug Administration has approved RIV for reducing the risk of major cardiovascular events in people with chronic coronary or peripheral artery diseases. However, it is important to determine the mechanism by which RIV suppresses atherosclerosis to establish RIV as a novel anti-atherosclerotic drug worldwide. Current findings may provide strong evidence for the clinical use of RIV through a better understanding of how it actually works. This increased clarity may help us turn the corner in treating one of the worlds most notorious diseases and alleviating the danger it presents to patients throughout the world.
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Materials provided by Tokyo Medical and Dental University. Note: Content may be edited for style and length.

During COVID-19 lockdowns, the internet was flooded with images from Delhi to Los Angeles, showing mountains typically hidden behind smog or clear blue skies where they were once gray.
People speculated that, because fewer people were driving, industry slowed and many airports were functionally closed, levels of pollution had dropped everywhere.
They had, depending on your vantage point.
Researchers from Washington University in St. Louis developed a method using satellite measurements that allowed them to determine levels of nitrogen dioxide — NO2 — on a scale never before accessible — even in areas where there are no monitoring capabilities on the ground. NO2 is a key contributor to the smog associated with bad traffic or areas of intense industry.
Developed in the lab of Randall Martin, the Raymond R. Tucker Distinguished Professor in the Department of Energy, Environmental & Chemical Engineering, the method allows researchers to infer levels of NO2 in regions as small as a neighborhood.
When they used it to compare levels of NO2 before and during COVID-19-related lockdowns across the globe, they found that, although there was a significant decrease in NO2 worldwide in areas under lockdown, there were also striking discrepancies on smaller scales.

Steroid estrogens play an important role as embryos develop a sense of smell, new research shows.
The study, which examined zebrafish embryos, discovered a type of astrocyte glial cell that is new to science, and have been named estrogen responsive olfactory bulb (EROB) cells.
estrogens are known for their roles as signalling hormones in the development of sex, but the study shows that prior to sexual differentiation (when the sex of an individual becomes fixed), a small group of cells in the region of the brain where the sense of smell develops, the olfactory bulb, are responsive to estrogen.
The research, led by Dr Aya Takesono of the University of Exeter, employed a genetically engineered (transgenic) zebrafish, developed in the laboratories of Professor Tyler and Dr Kudoh at Exeter, that enables cells and tissues responding to estrogen to be seen via microscopy imaging for this work.
Using this transgenic zebrafish, together with chemical and genetic methods to manipulate these estrogen responding cells, has revealed a new function of estrogens during embryonic brain development.
Dr Takesono said: “Previous studies in mice have shown that estrogen is important for development of the somatosensory cortex of the brain and for establishing sexual dimorphic brain tissues that mediate reproductive functions and behaviour in later life.

A high protein diet appears linked to kidney disease and shortened lifespans for captive polar bears, a relationship similarly suspected in humans, according to a review led by Washington State University wildlife biologist Charlie Robbins.
The paper, published in Zoo Biology, takes careful look at what zoos have fed polar bears revealing they mostly offered a diet intended for big cats, containing about 2-3 parts protein to 1-part fat, a reversal from what was observed in the wild.
“Zoos made some assumptions in the past about the nutritional requirements of polar bears because their diet is almost exclusively animals,” said Robbins, professor and founder of WSU’s Bear Center. “But, unlike cats, they do not need and cannot tolerate high protein.”
Polar bears feed almost solely on seals and are classified as carnivores. But recent research has demonstrated that polar bears, like other bears, have nutrition and physiology more closely aligned with primates, including humans.
Previous field studies led by Karyn Rode, a former WSU Bear Center graduate student now with the U.S. Geological Survey, showed wild polar bears preferentially consume a diet that is 2 parts fat to 1 part protein which keeps their protein levels within the low range of their requirements. These findings were published in Scientific Reports in July 2021.
“Although we knew that polar bears selected for the blubber of their prey, this was the first time we were able to quantify how much fat they were actually consuming,” Robbins said. “When it comes to feeding polar bears, the general mindset has been that they are carnivores. No one has really been paying attention to the amount of protein they might need, much less limitations on how much they might tolerate.”
In the current paper, the researchers propose that both polar bears and their closest relative, the grizzly bear, require relatively low levels of protein similar to requirements of humans, primates and other omnivorous species.

The omicron variant can partly evade the antibody response provided by vaccination or infection with previous variants of SARS-CoV-2. However, T cells still recognise omicron, scientists at Karolinska Institutet in Sweden report in a study published in the journal Nature Medicine.
Omicron has rapidly become the dominant variant of the SARS-CoV-2 virus. New data indicate that omicron is not only more infectious than previous variants, it can also infect people with previous immunity by evading what are known as neutralising antibodies.
Serious disease seems, however, to be relatively uncommon in people who have been vaccinated or infected, suggesting that other components of the immune system are still able to recognise omicron. A new study by researchers at Karolinska Institutet now shows that so-called memory T cells formed following previous infection or mRNA vaccination also respond to the omicron variant.
“Along with viral factors, such as a lower level of viral replication in the lower airways, and other immune components, these results give us a clearer picture that may explain why the protection against severe omicron disease remains good in previously mRNA-vaccinated individuals,” says principal investigator Marcus Buggert at Karolinska Institutet’s Center for Infectious Medicine.
The study is a collaboration with the Karolinska University Hospital in Sweden and is based on blood samples from 40 vaccinated individuals, 48 individuals who had had a mild or severe SARS-CoV-2 infection, and 48 individuals who had previously been neither vaccinated nor infected. The samples from the vaccinated group were collected six months after their second vaccine dose, and from the previously infected group 9 months after confirmed infection in the spring of 2020, prior to the emergence of the new viral variants. Other samples were taken from healthy donors at the end of 2020.
Memory T cells in both the experimental groups displayed a good ability to recognise the omicron spike protein; the best response, however, was observed in the vaccinated group.
“These results suggest that booster immunisation may provide benefits that extend beyond the induction of neutralising antibodies to enhance protection against recurrent episodes of severe COVID-19,” says Dr Buggert.
Even though the memory T-cell response was generally intact against omicron, some individuals did not respond as well.
“We now want to understand why the response differs from one individual to the next and if a third vaccine dose can augment the T cell response to omicron even more,” he says.
The study was financed with support from the SciLifeLab/KAW National COVID-19 Research Program (financed by the Knut and Alice Wallenberg Foundation), the Swedish Research Council, Nordstjernan AB, The Swedish Cancer Society, the Swedish Childhood Cancer Fund, the Åke Wiberg Foundation, the Swedish Society of Medicine, Region Stockholm and Karolinska Institutet. Marcus Buggert is consultant at Oxford Immunotec. KI researcher and co-author Soo Aleman has received fees from Gilead, AbbVie, MSD and Biogen and research grants from Gilead and AbbVie. Co-author Alessandro Sette at La Jolla Institute is a consultant at Gritstone Bio, Flow Pharma, Arcturus Therapeutics, ImmunoScape, CellCarta, Avalia, Moderna, Fortress and Repertoire. La Jolla Institute has applied for a patent relating to different aspects of the T-cell epitope and vaccine design.
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To stop acute myeloid leukemia, one of the deadliest blood cancers, targeting neighboring bone cells may be a better strategy than directly targeting the cells that give rise to the disease, suggests a new Columbia study.
The new study was published Jan. 19 in Cancer Discovery, a journal of the American Association for Cancer Research.
Acute myeloid leukemia (AML) is one of the hardest-to-treat blood cancers. And though it’s possible to achieve remission with drugs that target and destroy the stem cells that give rise to leukemia, the disease usually returns with deadly consequences. Patients relapse when new types of leukemic stem cells that elude all existing treatments surface.
Trying to develop additional drugs that target new stem cells is challenging, says cancer researcher Stavroula Kousteni, PhD, because the cancer will eventually mutate to circumvent the drugs.
Her new study shows that targeting neighboring cells in the bone marrow — osteoblasts, the cells which make bone — could turn a friendly environment for leukemia cells into a hostile one.
That’s because the osteoblasts are lured into helping leukemia stem cells, Kousteni’s team, led by Marta Galán-Díez, PhD, found. The new study reveals how leukemia cells lure the osteoblasts to function to their advantage by releasing a molecule called kynurenine. Kynurenine binds to a serotonin receptor (HTR1B) on the osteoblasts, sending the message to osteoblasts to help nurture leukemic cells by secreting an acute phase response protein (SAA1). SAA1 then tells the leukemia cells to make more kynurenine, and a vicious cycle ensues that leads to more disease progression.
The crosstalk between leukemia cells and osteoblasts can be broken, Galán-Díez and Kousteni found, suggesting a way forward for new AML treatments. In experiments with mice, they found that genetically eliminating the serotonin receptor that binds kynurenine blocks the progression of leukemic cells.
And in humanized mice carrying leukemia cells from patients and experiencing an AML relapse, an experimental drug that inhibits kynurenine synthesis “had a substantial effect in combination with traditional chemotherapy, slowing disease progression,” Galán-Díez says. (The drug, called epacadostat, is being tested in other cancers).
In the same study, Kousteni and Galán-Díez observed increasing levels of kynurenine and SAA1 in AML patients and in patients with myelodysplastic syndrome (MDS), another hematological cancer that often transforms to AML. Levels of both molecules increase with MDS progression to AML and SAA1 promotes proliferation of MDS and AML cells from patients, suggesting the same partnership between MDS or leukemia cells and osteoblasts is active in the human form of disease.
“The advantage of this approach is that it doesn’t matter which stem cells are causing the disease. They all need osteoblasts to grow, and if we can stop these two types of cells from communicating, we might be able to stop the disease,” Kousteni says.
In addition, the same approach may also prevent pre-leukemic conditions like MDS from progressing.
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