Publisher Health

Ensuring COVID-19 vaccine access for refugee and displaced populations, and addressing health inequities, is vital for an effective pandemic response. Yet, vaccine allocation and distribution has been neither equitable nor inclusive, despite that global leaders have stressed this as a critical aspect to globally overcoming the pandemic, according to a paper published by Columbia University Mailman School of Public Health. Read “Leave No-one Behind: Ensuring Access to COVID-19 vaccines for Refugee and Displaced Populations” in the journal Nature Medicine.
As of April 1st, high and upper-middle-income countries received 86 percent of the vaccine doses delivered worldwide, while only 0.1 percent of doses have been delivered in low-income countries. Worldwide, over 80 percent of refugees and nearly all internally displaced persons are hosted by low and middle-income countries — nations at the end of the line for COVID-19 vaccine doses.
“As the world grapples with supply challenges and inequitable vaccine access on local and global scales, marginalized groups, particularly refugees, internally displaced persons and stateless persons, face a double burden of access, even within countries that are themselves marginalized on the global stage,” said Monette Zard, MA, Allan Rosenfield Associate Professor of Forced Migration and Health and director of the forced migration and health program at Columbia Mailman School. “Legal status should have no place in decisions about vaccine access, and relying on regularization as a route to vaccination will unacceptably delay the protective effects for migrants and refugees, particularly in higher risk groups.”
In fragile settings with weak governance, competition for scarce COVID-19 vaccines may heighten tensions and exacerbate conflict, while unequal access raises the prospect of populations moving in an effort to access vaccines that are not available in their country or region, according to the authors.
The COVAX facility allocates around 5 percent of total available vaccine doses for humanitarian use, including vaccinating refugees, yet the total 2 billion vaccine doses targeted by the end of 2021 will only cover 20 percent of participating countries’ populations, at most. Poorer countries may not be able to widely vaccinate their populations until 2023.
To create an equitable and inclusive COVID-19 vaccination strategy, Zard and co-authors believe lessons can also be drawn from experience managing conditions such as HIV and TB among mobile populations, as well as previous large-scale vaccination campaigns in humanitarian settings. They point out how the global community approaches COVID-19 vaccinations may further entrench the inequities and distrust experienced by refugees and displaced populations around the world or is a chance to build stronger, fairer health systems that are better prepared to respond to COVID-19 and future health emergencies. “Engage, listen, and mobilize trusted community and religious leaders — involving the community, including displaced populations, in vaccine activities is vital,”noted Zard.
“Policy makers need to seize the opportunity of the pandemic to strengthen health systems more broadly and sustainably, to better respond to the challenges of COVID-19, while addressing the comprehensive health needs of refugees and host populations,” observes one of the authors S. Patrick Kachur, MD, professor of population and family health at Columbia Mailman School. “As the world confronts one of the most formidable public health challenges in recent history, how we respond today will not only determine the course of this pandemic, but also who benefits from public health advances for years to come.”
Co-authors are: Ling San Lau, Goleen Samari, Rachel Moresky, Mhd Nour Audi, and Claire Greene, Program on Forced and Migration and Health, Columbia Mailman School; Diana M. Bowser and Donald Shepard, Brandeis University; Fouad M. Fouad, American University of Beirut; Diego Lucumí and Arturo Harker, Universidad de los Andes; and Wu Zeng, Georgetown University.

At the end of 2020, experts led by allergists at Massachusetts General Hospital (MGH) examined all information related to possible allergic reactions to COVID-19 vaccinations. Now the team has published updated insights based on their experience overseeing more than 65,000 employees who have become fully vaccinated since that time. The group’s latest findings are published in the Journal of Allergy and Clinical Immunology: In Practice.
“Our main goal is to enable as many individuals as possible to receive a COVID-19 vaccine safely and avoid unnecessary vaccine hesitancy due to a lack of knowledge around allergic reactions to vaccines,” says lead author Aleena Banerji, MD, clinical director of the Allergy and Clinical Immunology Unit at MGH.
In addition to updated guidance on the Pfizer-BioNTech and Moderna COVID-19 vaccines, this guidance also includes the Janssen COVID-19 vaccine, which had not yet been authorized for emergency use at the end of 2020.
With additional clinical data and authorization of the third COVID-19 vaccine in the United States, the investigators propose modified approaches to the evaluation of patients with a history of allergies. This includes clear and simple initial questions to identify individuals who are eligible for all COVID-19 vaccines without needing an allergist evaluation.
“With more time and experience, we have been able to significantly narrow the group of patients with prior allergies who require an allergist assessment before COVID-19 vaccination,” says senior author Kimberly G. Blumenthal, MD, MSc, co-director of the Clinical Epidemiology Program within MGH’s Division of Rheumatology, Allergy and Immunology. “We now advise that only the rare individuals who have had a recent severe allergic reaction to polyethylene glycol, an ingredient in the vaccines, see an allergist or immunologist for evaluation, which may include skin testing.” Individuals with severe allergies to foods, oral drugs, latex, bee stings or venom can safely receive the COVID-19 vaccines.
The team noted that severe allergic reactions to the vaccines remain exceedingly rare. Vaccine clinics should continue to observe higher-risk individuals for 30 minutes after vaccination, and they should have staff trained in recognizing and managing allergic reactions that may occur.
Story Source:
Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.

Researchers at Albert Einstein College of Medicine have developed a topical drug that regenerates and restores the function of erectile nerves damaged by radical prostatectomy, the most common treatment for localized prostate cancer. The drug was tested in rats, and the findings were published online today in JCI Insight.
“Erectile dysfunction (ED) after radical prostatectomy has a major impact on the lives of many patients and their partners,” said study co-leader David J. Sharp, Ph.D., professor of physiology & biophysics and of ophthalmology and visual sciences and professor in the Dominick P. Purpura Department of Neuroscience at Einstein. “Since rats are reliable animal models in urologic research, our drug offers real hope of normal sexual function for the tens of thousands of men who undergo this surgery each year.”
Radical prostatectomy — surgery to remove the prostate gland — is considered the definitive treatment for localized prostate cancer. “Despite the advent of so-called nerve-sparing procedures, the surgery can damage the cavernous nerves, which control erectile function by regulating blood flow to the penis,” said study co-leader Kelvin P. Davies, Ph.D., professor of urology and of physiology & biophysics at Einstein. He notes that about 60% of patients report having ED 18 months after surgery, and fewer than 30% have erections firm enough for intercourse after five years. Viagra and similar ED treatments are rarely effective in these patients, he said.
A decade ago, Dr. Sharp and colleagues discovered that the enzyme fidgetin-like 2 (FL2) puts the brakes on skin cells as they migrate towards wounds to heal them. To speed wound healing, the researchers developed an “anti-FL2” drug: small interfering RNA molecules (siRNAs) that inhibit the gene that codes for FL2. Packaged in gel nanoparticles and sprayed on mice, the siRNAs not only healed wounds twice as fast as untreated wounds but also regenerated damaged tissue. A February 2021 study in rats found that the siRNAs also aided the healing of corneal alkaline burns.
Dr. Sharp, Dr. Davies, and their teams realized that injured nerves might be especially amenable to this gene-silencing drug: For unknown reasons, the FL2 gene becomes over-active after injury to nerve cells, causing the cells to produce copious amounts of FL2 enzyme.
The Einstein team evaluated the drug using rat models of peripheral nerve injury in which the cavernous nerves were either crushed or severed, mimicking the nerve damage associated with radical prostatectomy. The siRNA gel was applied to the nerves immediately after injury.

Having an epidural during childbirth is not associated with a greater risk of autism in the child, according to a study led by researchers at the Stanford University School of Medicine and the University of Manitoba.
The study, which will publish online April 19 in JAMA Pediatrics, helps resolve questions raised by an earlier, widely criticized report on the topic.
“We did not find evidence for any genuine link between having an epidural and putting your baby at increased risk of autism spectrum disorder,” said the study’s senior author, Alexander Butwick, MD, associate professor of anesthesiology, perioperative and pain medicine at Stanford. The study should help reassure both physicians and pregnant women about the favorable safety profile of epidurals, he added.
Epidurals are the most common form of pain relief for childbirth, used by about three-quarters of women in labor in the United States. Autism is a developmental disorder that affects one in every 54 children nationwide.
“The epidural is the gold standard in labor pain management,” said the study’s lead author, Elizabeth Wall-Wieler, PhD, assistant professor at the University of Manitoba. “The vast majority of evidence around epidurals, including that from our new study, shows that they are the most effective means of providing pain relief to women during labor and that serious complications are rare.”
Questions raised by prior study
During an epidural, anesthetic is given by catheter into the space around the woman’s spinal cord. Epidurals relieve pain from labor contractions while allowing women to stay alert and push during birth. They also have other important, yet underappreciated, advantages. For example, epidurals can provide anesthesia to laboring women who require unplanned, and often urgent, cesarean sections. They also pose a lower risk to the mother and baby than general anesthesia, which may be necessary if a woman who has not already had an epidural needs an emergency C-section.

Researchers and physicians from the Occupational Safety and Health Administration (OSHA) and UC San Francisco have found that deaths of workers using methylene chloride paint strippers are on the rise. The solvent is widely used in paint strippers, cleaners, adhesives and sealants.
The study is the first comprehensive review of fatalities linked to the deadly chemical in the United States and identified more deaths than previously reported.
The Environmental Protection Agency (EPA) has acknowledged 53 fatalities connected to the chemical from 1980 to 2018. The new study identified 85 deaths over the same period, most of them occurring in occupational settings (87 percent). The study is published April 19, 2021, in JAMA Internal Medicine.
The authors urged action from the EPA to limit use of the chemical and prevent future deaths.
“It is unacceptable that these workers died simply because they were doing their job,” said lead author Annie Hoang, a UCSF medical student and research fellow at UCSF’s Program on Reproductive Health and the Environment. “I hope the EPA will do its job to protect our workers and save lives.”
The researchers believe that methylene chloride fatalities are undercounted in the United States due to fragmented public health reporting. To identify deaths from the chemical, the researchers undertook a massive search of different sources, including published scientific papers and government databases, compiling information that included medical records and autopsy findings, where available. Their analysis found an increase since 2000 in occupational fatalities related to both paint stripping and to bathroom construction, due to stripping bathtubs.
In early 2017, EPA proposed a rule banning almost all methylene chloride strippers in both the workplace and for consumer use. But in 2019 under new leadership, EPA limited the ban to consumer products while still allowing commercial use to continue unchecked.
“Based on our findings, workers are still at risk from methylene chloride products,” said Kathleen Fagan, MD, MPH, former Medical Officer in the Office of Occupational Medicine and Nursing at OSHA and one of the study’s researchers. “Health care providers have a critical role to play in preventing deaths by counseling at-risk patients on risk reduction and providing resources on safer alternatives to methylene chloride.”
The paper reported that while regulatory policies over the last 25 years mandated product labeling and worker protections, fatalities continued during that time, with a higher proportion of recent deaths tied to the use of paint stripping products. The vast majority of deaths were among men (93.8 percent). Of the 85 fatalities, in 70 cases that had specific information about age, the median age was 31.
The researchers concluded that despite regulatory efforts to address the toxicity of methylene chloride for consumers and workers, fatalities are continuing in the U.S., particularly in occupational settings. They said that prevention should emphasize safer substitutes, not hazard warnings or reliance on personal protective equipment.
“Safer alternatives to methylene chloride are available and in widespread use,” said senior author Veena Singla, PhD, a senior scientist at the Natural Resources Defense Council. Previously, she was director of science and policy with UCSF’s Program on Reproductive Health and the Environment.
“The science is clear,” Singla said. “It is past time to eliminate this deadly chemical and prevent any further tragic loss of life.”
Story Source:
Materials provided by University of California – San Francisco. Original written by Elizabeth Fernandez. Note: Content may be edited for style and length.

Someday, scientists believe, tiny DNA-based robots and other nanodevices will deliver medicine inside our bodies, detect the presence of deadly pathogens, and help manufacture increasingly smaller electronics.
Researchers took a big step toward that future by developing a new tool that can design much more complex DNA robots and nanodevices than were ever possible before in a fraction of the time.
In a paper published today (April 19, 2021) in the journal Nature Materials, researchers from The Ohio State University — led by former engineering doctoral student Chao-Min Huang — unveiled new software they call MagicDNA.
The software helps researchers design ways to take tiny strands of DNA and combine them into complex structures with parts like rotors and hinges that can move and complete a variety of tasks, including drug delivery.
Researchers have been doing this for a number of years with slower tools with tedious manual steps, said Carlos Castro, co-author of the study and associate professor of mechanical and aerospace engineering at Ohio State.
“But now, nanodevices that may have taken us several days to design before now take us just a few minutes,” Castro said.

It has been known for about a year that minks can become infected with SARS-CoV-2. The virus had been transmitted from humans to farmed mink and mutated in infected animals. Mutations were acquired in the spike protein, which is crucial for the entry of the virus into host cells and represents the central point of attack for antibodies. These SARS-CoV-2 variants from mink were transmitted back to humans, raising concerns that minks could be a continuing source of infection of humans with SARS-CoV-2 variants with altered biological properties.
Researchers at the German Primate Center (DPZ) — Leibniz Institute for Primate Research in Göttingen, Germany, have now shown that an antibody used for COVID-19 therapy is unable to effectively inhibit SARS-CoV-2 harboring a spike mutation acquired in minks. In addition, the mutation reduced the inhibition of the virus by antibodies produced in SARS-CoV-2 infected humans. These results show that SARS-CoV-2 can acquire mutations in minks that may reduce control of the virus by the human immune system (Cell Reports).
More than three million people have died worldwide from the pandemic spread of SARS coronavirus-2 and its associated disease COVID-19, according to the World Health Organization (WHO). Animal-to-human transmission of the virus is believed to be the origin of the pandemic, which began in Wuhan, China, in December 2019. In April 2020, mink in Dutch mink farms developed a respiratory disease due to infection with SARS-CoV-2, which was transmitted from infected farm workers to the animals. The virus mutated in mink and different virus variants emerged, which were transmitted back to farm workers and then also transmitted from human to human. This observation was also made in Denmark and millions of minks were killed to prevent the transmission of new viral variants to humans.
The spike protein in the envelope of SARS-CoV-2 is responsible for the entry of the virus into cells in which it replicates. Researchers led by Markus Hoffmann and Stefan Pöhlmann of the German Primate Center have studied mutations detected in the spike protein of SARS-CoV-2 from mink, including mutation Y453F. The researchers wanted to find out whether this mutation affects inhibition of the virus by antibodies that are used for COVID-19 therapy or are produced in COVID-19 patients.
“Our results show that one of two antibodies from an antibody cocktail used for COVID-19 therapy no longer efficiently inhibits the viral variant with the Y453F mutation. Furthermore, our study demonstrates that the Y453F mutation reduces inhibition of the virus by antibodies produced by COVID-19 patients. This means that people who were infected with SARS-CoV-2 may have reduced protection against mink variants of the virus,” says Markus Hoffmann, first author of the study. In sum, SARS-CoV-2 can mutate in minks in a way that reduces immune control by antibodies. Whether this is also possible in other animals to which the virus can be transmitted by infected individuals is currently unclear. “In the meantime, the Y453F mutation has also occurred in humans, but not through infection with a mink variant. When the virus replicates for a long time in people who are immunocompromised, resistant variants can emerge. In this case, the resistance-mediating mutation was identical to the one observed in mink,” says Stefan Pöhlmann.
Story Source:
Materials provided by Deutsches Primatenzentrum (DPZ)/German Primate Center. Note: Content may be edited for style and length.

More blood thinners aren’t automatically better, another study confirms.
A new publication in JAMA Internal Medicine focuses on the minimal pros and the concerning cons of combining a daily aspirin with a drug from the newer class of anticoagulants that include apixaban, dabigatran, edoxaban and rivaroxaban.
Patients were taking one of these direct oral anticoagulants known as DOACs to prevent strokes from non-valvular atrial fibrillation or for the treatment of venous thromboembolic disease (deep vein thrombosis or pulmonary embolism). The included patients did not have another reason to take aspirin such as a recent history of a heart attack or a history of a heart valve replacement. The researchers discovered that almost one-third of the people who were prescribed a DOAC were also taking aspirin without a clear reason for the aspirin.
“The patients on combination therapy were more likely to have bleeding events but they weren’t less likely to have a blood clot,” says lead author Jordan Schaefer, M.D., an assistant professor of internal medicine and a hematologist at Michigan Medicine, the academic medical center of the University of Michigan. “Therefore, it’s important that patients ask their doctors if they should be taking aspirin when they are prescribed a direct oral anticoagulant.”
The combination of an anticoagulant and an antiplatelet may be appropriate for people who have had a recent heart attack, recent coronary stent placement or bypass surgery, prior mechanical valve surgery or known peripheral artery disease, among other conditions says co-author Geoffrey Barnes, M.D., M.Sc., an assistant professor of internal medicine and a vascular cardiologist at the Michigan Medicine Frankel Cardiovascular Center.
For the others, “combination therapy may not be happening intentionally; rather, the addition of aspirin might get overlooked because it’s not in any one specialist or general care provider’s territory,” Barnes says.
The authors note that there are many medical conditions and situations where adding aspirin with a direct oral anticoagulant has not been adequately studied. Schaefer adds that they plan to confirm their study findings in a larger, longer study because there were not many blood clots that occurred during the timeframe of this study, potentially limiting their ability to assess if aspirin could be beneficial.
Previously, Schaefer and Barnes also reported a significant increase in adverse outcomes for people taking both aspirin and warfarin, a different kind of anticoagulant.
Schaefer originally presented these registry-based cohort study results at the 2019 annual meeting of the American Society of Hematology.
Story Source:
Materials provided by Michigan Medicine – University of Michigan. Original written by Haley Otman. Note: Content may be edited for style and length.

A new gene therapy for one of the most common forms of congenital blindness was safe and improved patients’ vision, according to initial data from a clinical trial led by researchers at the Scheie Eye Institute in the Perelman School of Medicine at the University of Pennsylvania.
The therapy delivers working copies of GUCY2D to the eyes of patients who have severe vision impairments caused by mutations in the gene. Each of the first three treated patients experienced improvement in some aspects of vision, without serious side effects, according to the new study, published in the journal iScience.
“We found sustained improvements in both day and night vision, even with a relatively low dose of the gene therapy,” said study lead author Samuel G. Jacobson, MD, PhD, a professor of Ophthalmology in the Perelman School of Medicine.
The GUCY2D gene is one of about 25 different human genes whose mutations cause problems in the retina, leading to severe vision impairment from birth or early childhood. This family of inherited retinal disorders, collectively known as Leber congenital amaurosis (LCA), accounts for a considerable portion of blindness in children worldwide.
Normal copies of GUCY2D encode an enzyme in the key pathway that light-sensitive rod and cone cells in the retina use to convert light into electrochemical signals. A lack of this enzyme blocks the recovery of this pathway, preventing the reset needed for further signaling. As a result, the signal from rod and cone cells becomes very weak — which equates to severe vision loss.
Even in adults who have lived for decades with this condition, it is often the case that many light-sensing retinal cells remain alive and intact despite their dysfunction. Thus, adding functional copies of GUCY2D via a gene therapy could get those cells working again and restore some vision.
In 2019, Jacobson and co-investigator Artur V. Cideciyan, PhD, a research professor of Ophthalmology in the Perelman School of Medicine, began the first clinical trial of a GUCY2D gene therapy, a solution of a harmless virus that carries the gene and is injected beneath the retina — initially in just one eye per patient. They are following each patient for two years after treatment. In the new report, they described their findings after nine months in the first three patients treated.
The first patient experienced a substantial increase in light-sensitivity in rod cells, which are more light-sensitive than cone cells and are chiefly responsible for low-light or “night vision.” This patient also showed improved pupil responses to light.
The second patient showed a smaller but sustained increase in light-sensitivity in rod cells, starting about two months after the gene therapy.
The third patient showed no improvement in rod cell sensitivity, but did show significantly improved visual acuity over the nine-month follow-up period, an improvement that the researchers tied to better function in the patient’s cone cells, the predominant cells for daylight and color vision.
“These initial results from the first-ever trial of a GUCY2D gene therapy are very encouraging and will inform our ongoing and future trials of this therapy,” said Cideciyan. There were no serious adverse side effects, and any side effects that occurred in the patients’ retinas resolved.
The gene therapy dose used in these first three patients was the lowest of the doses the researchers plan to use in the study, so they are hoping to see continued safety and greater efficacy in later-enrolled patients who will receive higher doses.

Despite access to some of the best possible medical care in the world, Senators John McCain and Edward Kennedy both died within 18 months of their diagnosis of glioblastoma, an aggressive form of brain cancer. While this deadly outcome typifies the nature of this disease, some glioblastoma patients see exceptional benefits from chemotherapy and survive beyond expectations. Why this happens has been revealed by researchers at the University of Minnesota in a new study published in the Proceedings of the National Academy of Sciences.
“Deciphering the molecular underpinning of these exceptional responses may hold the key to transforming the hope for miracles into the reality of an expected cure for glioblastoma patients,” said Clark C. Chen, MD, PhD, Lyle French Chair in Neurosurgery and head of the Department of Neurosurgery at the University of Minnesota Medical School, who is also lead author of the study.
The study team looked at the gene expression profiles of glioblastoma specimens collected from approximately 900 glioblastoma patients from regions across the world to identify unique features associated with exceptional responders, defined as glioblastoma patients who survive more than two years after treatment.
“We utilized different state-of-the-art analytics to study these samples, including methods innovated by Dr. Aaron Sarver, a member of the University of Minnesota Institute of Health Informatics. Impressively, these analytics converged on a single observation, a paucity of microglia and macrophages,” Chen said.
Microglia and macrophages are specialized, immune cells that act as scavengers to recognize and remove cells not normally present in a healthy brain, including cancer cells. These immune cells migrate to sites harboring abnormal cancer cells to defend the body against the cancer cells and can make up more than half of the cells in a glioblastoma sample.
“If microglia and macrophages normally fend off cancer cells, more of them should allow the body to better fend off the tumor. So, we expected to see more of them in the exceptional responders; however, we found the contrary,” said Jun Ma, a researcher in the Department of Neurosurgery at the U of M Medical School and a co-first author of this study.
Resolving this paradox, the research team subsequently demonstrated glioblastoma cells possess the capacity to recondition the surrounding microglia and macrophages and corrupt their native anticancer functions. Instead of fending off cancer growth, these immune cells are now re-programmed by glioblastoma cells to promote tumor growth.
“It is frightening to consider the possibility that cancer cells can ‘brainwash’ our own immune cells and convert them from cells that fight cancer to cells that promote cancer,” said Judith Varner, a co-senior author of the study and professor of pathology at the University of California, San Diego. “Fortunately, we have figured out how glioblastoma cells subvert our immune system and can now reverse this cellular version of the ‘Stockholm syndrome.'”
Stockholm syndrome is a psychological response in which hostages or abuse victims develop an emotional bond with and act to help their captors.
The key to curing this cellular “Stockholm syndrome” and possibly glioblastoma lies in a protein called phosphoinositide-3-kinase gamma isoform (PI3K?). Activation of this protein turns microglia and macrophages from immune cells that police cancer growth into hostage cells that promote cancer growth. Varner has studied this process for many years and pioneered drugs that restore the anti-tumor activities of microglia and macrophages.
“In our animal glioblastoma models, treatment with drugs targeting PI3K? consistently resulted in impressively durable responses to chemotherapy,” Chen said. “We are eager to translate these findings into a human trial, with the hope of transforming every glioblastoma patient into an exceptional responder.”
Story Source:
Materials provided by University of Minnesota Medical School. Original written by Kelly Glynn. Note: Content may be edited for style and length.