The coronavirus pandemic has had an impact on everyone’s mental wellbeing but those on the front line of dealing with it have suffered more than most. BBC Health reporter Laura Foster talks to three doctors in the NHS for their tips on how you can help support health and care workers with their mental health.Video by Laura Foster and Mel Lou

As eligibility for Covid-19 vaccination rapidly expands to all adults in many states over the next month, a new poll shows a continuing increase in the number of Americans, particularly Black adults, who want to get vaccinated. But it also found that vaccine skepticism remains stubbornly persistent, particularly among Republicans and white evangelical Christians, an issue that the Biden administration has flagged as an impediment to achieving herd immunity and a return to normal life.By now, roughly 61 percent of adults have either received their first dose or are eager for one, up from 47 percent in January, according to the latest monthly survey by the Kaiser Family Foundation.The shift was most striking among Black Americans, some of whom have previously expressed hesitancy but who have also had access issues. Since just February, 14 percent more Black adults said they wanted or had already gotten the vaccine. Over all, Black adults, who have also been on the receiving end of vigorous promotional campaigns by celebrities, local Black physicians, clergy members and public health officials, now want the vaccine in numbers almost comparable to other leading demographic groups: 55 percent, compared with 61 percent for Latinos and 64 percent for white people.The Biden administration has made equity a focus of its pandemic response and has added mass vaccination sites in several underserved communities. In early March, a New York Times analysis of state-reported race and ethnicity information showed that the vaccination rate for Black people in the United States was half that of white people, and the gap for Hispanic people was even larger.Dr. Reed Tuckson, a founder of the Black Coalition Against Covid, hailed the increasing acceptance rates but noted that practical problems still get in the way of uptake.“The data, and our anecdotal feedback, are encouraging and further support the need for equitable distribution and easy-to-access vaccination sites that are led by trustworthy organizations,” he said. “The system needs to support those choices by making the right thing to do the easy thing to do.”Over all, the poll found that the so-called wait and see group — people who have yet to make up their mind — is shrinking commensurately, now at 17 percent, down from 31 percent in January. The seven-day average of vaccines administered hit 2.77 million on Tuesday, an increase over the pace the previous week, according to data reported by the Centers for Disease Control and Prevention.The survey was taken between March 15 through March 22, among a random sample of 1862 adults.Despite the progress, one in five adults (20 percent) say they would either definitely refuse the shot or only be vaccinated if required by their job or school. A number of employers and institutions are considering imposing such a requirement. Last week, Rutgers University became the first large academic institution to require students this fall to get the vaccine (with exemptions for some medical or religious reasons).The people most likely to firmly oppose being vaccinated identify as Republicans (29 percent) or as white evangelical Christians (28 percent). In contrast, only 10 percent of Black adults said they would definitely not get it.According to the Kaiser survey as well as other polls, Republicans have budged little in their views on vaccine acceptance in recent months, although they were more open last fall, before the November presidential election. The partisan divide over the Covid shots is wide, with just 46 percent of Republicans saying they have received at least one shot or want to get it, compared with 79 percent of Democrats.No group is monolithic in its reasons to oppose or accept the vaccines. Those who are skeptical say they mistrust the government generally and are apprehensive about the speed of the vaccine’s development. Awash in online misinformation, many cling to a fast-spreading myth — that tracker microchips are embedded in the shots.For rural residents, access to the vaccine is so problematic that they see the logistics and travel time involved as simply not worth it.With so many reasons cited to avoid the vaccine, crafting messages to coax vaccine confidence can be difficult. But the latest Kaiser report identified some approaches that seem to be successful in moving people to consider the shots.At least two-thirds of the so-called wait and see group said they would be persuaded by the message that the vaccines are “nearly 100 percent effective at preventing hospitalization and death from Covid-19.” Other strong messages included information that the new vaccines are based on 20-year-old technology, that the vaccine trials included a broad diversity of candidates, and that the vaccines are free.The survey also noted that many people who are hesitant would be amenable to certain incentives. As the country begins to open up and on-site work returns, the role of the employer in vaccination is becoming increasingly pertinent. A quarter of those who are hesitant and have a job said that they would get the shot if their employer arranged for workplace vaccination. Nearly as many would agree if their employers gave them financial incentives ranging from $50 to $200.But over all, the strong growth in adults who have either gotten one dose of the vaccine or are inclined to get it is most likely because of their increasing familiarity with the notion. Surveys show that as they begin to know more friends and relatives who have gotten the shot, they can more readily imagine getting it themselves.See How the Vaccine Rollout Is Going in Your County and StateSee where doses have gone, and who is eligible for a shot in each state.

COVID-19 can have damaging effects on multiple organs in the body, including the brain. A new study led by investigators at Massachusetts General Hospital (MGH) and Beth Israel Deaconess Medical Center (BIDMC) indicates that some hospitalized patients with COVID-19 experience non-convulsive seizures, which may put them at a higher risk of dying. The findings are published in the Annals of Neurology.
“Seizures are a very common complication of severe critical illness. Most of these seizures are not obvious: Unlike seizures that make a person fall down and shake, or convulse, seizures in critically ill patients are usually nonconvulsive,” explains co-senior author M. Brandon Westover, MD, PhD, an investigator in the Department of Neurology at MGH and director of Data Science at the MGH McCance Center for Brain Health. “There is increasing evidence that non-convulsive seizures can damage the brain and make outcomes worse, similar to convulsions.”
Westover notes that there have been only a few small reports of seizures in patients with severe COVID-19 illness, and it was previously unclear whether such seizures primarily occur in patients who already have a seizure disorder or whether they can arise for the first time because of COVID-19. The effects of such seizures on patients’ health was also unknown.
To provide insights, Westover and his colleagues analyzed medical information for 197 hospitalized patients with COVID-19 who underwent electroencephalogram (EEG) monitoring — tests that detect electrical activity of the brain using small metal discs attached to the scalp — for various reasons at nine institutions in North America and Europe.
The EEG tests detected nonconvulsive seizures in 9.6% of patients, some of whom had no prior neurological problems. Patients who had seizures needed to be hospitalized for a longer time, and they were four times more likely to die while in the hospital than patients without seizures — suggesting that neurological complications may be an important contributor to the morbidity and mortality associated with COVID-19.
“We found that seizures indeed can happen in patients with COVID-19 critical illness, even those without any prior neurologic history, and that they are associated with worse outcomes: higher rates of death and longer hospital stay, even after adjusting for other factors,” says co-senior author Mouhsin Shafi, MD, PhD, an investigator in the Department of Neurology at BIDMC, medical director of the BIDMC EEG laboratory, and director of the Berenson-Allen Center for Noninvasive Brain Stimulation. “Our results suggest that patients with COVID-19 should be monitored closely for nonconvulsive seizures. Treatments are available and warranted in patients at high risk; however, further research is needed to clarify how aggressively to treat seizures in COVID-19.”
Westover is an associate professor of Neurology at Harvard Medical School (HMS) and Shafi is an assistant professor of Neurology at HMS.
This work was supported by the National Institutes of Health, the Football Players Health Study at Harvard University, the Glenn Foundation for Medical Research and the American Federation for Aging Research, the American Academy of Sleep Medicine, the Department of Defense, and the Eleanor and Miles Shore Fellowship.
Story Source:
Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.

A year ago scientists everywhere were scrambling to get their minds around the SARS-CoV-2, a novel coronavirus that caused the pandemic from which we are only now beginning to emerge. The world clung to every new development, every bit of science that could provide clues to managing life in the presence of this mysterious killer.
Many science-backed COVID-19 management concepts remain unchanged to this day: handwashing with soap and warm water disrupts the virus’ lipid membrane. Social distancing can attenuate the virus’s spread, ideally keeping it out of a host until it degrades. Other notions, such as droplet contact being the primary mode of transmission, were modified when emerging evidence showed that under certain conditions, the virus could remain suspended in air for extended periods of time.
In a letter in the Journal of Infectious Diseases, a team of researchers from UC Santa Barbara, Oregon State University, University of Manchester and ETH Zurich examines another of SARS-CoV-2’s well known characteristics — its vulnerability to sunlight. Their conclusion? It might take more than UV-B rays to explain sunlight inactivation of SARS-CoV-2.
The idea that an additional mechanism might be in play came when the team compared data from a July 2020 study(link is external) that reported rapid sunlight inactivation of SARS-CoV-2 in a lab setting, with a theory(link is external) of coronavirus inactivation by solar radiation that was published just a month earlier.
“The theory assumes that inactivation works by having UV-B hit the RNA of the virus, damaging it,” said UC Santa Barbara mechanical engineering professor and lead author Paolo Luzzatto-Fegiz(link is external). Judging from the discrepancies between the experimental results and the predictions of the theoretical model, however, the research team felt that RNA inactivation by UV-B “might not be the whole story.”
According to the letter, the experiments demonstrated virus inactivation times of about 10-20 minutes — much faster than predicted by the theory.

The magazine’s Ethicist columnist on balancing health care providers’ privacy against patients’ concerns, creating an equitable vaccine system and more.I was planning to make an appointment with a hygienist working under my dentist and was told by a third party that one of the hygienists had contracted Covid, been treated and was back to work. I am 69, and my nephew died of Covid last May. Four other relatives contracted the virus and recovered. I am nervous about the pandemic.I requested not to be treated by that hygienist and received this email in response: “To protect the privacy of our staff, just as we do for our patients, we cannot confirm or deny if someone has recovered from the coronavirus. This would be a violation of HIPAA. Your request to not be seen by someone who tested Covid-19 positive was not appropriate, as C.D.C. guidelines state that after 14 days of quarantine, individuals are safe to go out in public. In addition, our clinicians wear appropriate P.P.E. for treatment (including N95 masks, face shields, gowns, gloves), and our office has implemented additional infection-control measures. We monitor for symptoms, take temperatures and measure oxygen saturation daily for everyone that comes into our suite. If this policy makes you uncomfortable, our office may not be a good fit for you.”I have a problem with putting the privacy of an employee ahead of the concerns of a patient. I also thought that HIPAA applied only to disclosures by a doctor about their patients. Am I out of line to make this request? Should a doctor or dentist tell patients if a staff member has had the virus so that the patient can make an informed decision about treatment? Jack L. Schwartz, Los AngelesAll employers, including medical employers like your dentist, are entitled to have certain kinds of health information about employees. But, like health care providers, they should generally keep that information confidential. It’s granted to them for a limited class of purposes and should be seen only by people who require access to it for those reasons. (The federal rules are complicated, but the basic idea is that information about people’s health shouldn’t be given without their consent unless necessary.) Your dentist is entitled to know that employees are sick in order to confirm that they have medical reasons for taking sick days and to be sure that they pose no risks when they return to patient care. But precisely because the dentist was allowed the information necessary to decide whether the hygienist could safely be at work, patients in the clinic don’t need this information.The really important thing isn’t whether someone once had the virus but whether everyone in the clinic is taking the appropriate precautions with respect to hygiene and P.P.E. As it happens, people who have recovered from Covid-19 are thought to have immunity to it for some time, and people who have immunity to the virus are less likely to transmit it. So it doesn’t make sense to avoid a hygienist who has recovered. Someone who has never had the disease or has not been vaccinated poses the greater risk. (Though, again, a minimal one given proper precautions.)The C.D.C. says that someone who has had Covid-19 can be around others if 10 days have elapsed since symptoms began, a full day has elapsed without fever and other symptoms are improving. Although your dentist’s précis was inexact, it sounds as if the office erred on the side of safety and is rigorous about protocols. Your dentist was making the point that there was no clash here between employee privacy and the legitimate concerns of a patient. Possibly, though, I wouldn’t have added that slightly barbed final comment (“If this policy makes you uncomfortable, our office may not be a good fit for you”). Dentists, of all people, should understand the power and prevalence of irrational anxieties, and one element of good medicine is an understanding heart.I am a college student who spent my break working as an E.M.T. for a private ambulance service. My state’s Covid-19 vaccine protocol prioritizes first responders, and I have the option to receive a shot next week. Given that it can take up to a few weeks for the vaccine to promote antibodies, however, if I get the vaccine now, it won’t protect me until after I’m back at school. My early vaccination provides no benefit to the community, and I could be taking a dose from someone who is at greater risk. Is it wrong for me to get the vaccine knowing that if it weren’t for a few weeks of work, I would be waiting months? Elizabeth Hopkinson, MassachusettsA fair and reasonable system that isn’t unworkably complicated will end up vaccinating some people earlier than others whose need is greater. It’s not your job to add further criteria of your own. What’s more, the available evidence suggests that significant protection starts to kick in about 10 to 14 days after initial vaccination, which could overlap with your period of work as an E.M.T. And being vaccinated does provide a benefit to your community. It lowers the chance of your transmitting the disease by reducing the likelihood that you’ll contract it and, very likely, by reducing the likelihood that you’ll transmit it even if you do. Adding to the overall vaccination rate, which this does, will be necessary in order to reach something like herd immunity.An acquaintance asked me to refer him for an open position at my company. Normally, I would be happy to do so, but he mentioned that for New Year’s he rented a house in another state with a group of friends and later traveled to yet another state to ski. I think it is irresponsible of him to have engaged in recreational travel during the winter peak of the pandemic. The position he’s applying for is at a company where all employees currently work remotely. My concern is not that he’ll get anyone sick but that his recent travel indicates poor judgment, which may be obliquely relevant to his ability to do the job. Should I decline to refer him on these grounds or is that too big of a logical leap? Name WithheldYou’re not obliged to recommend an acquaintance for a job just because he asks. And if you do, you should not hide faults relevant to that job. But your resistance to recommending this person doesn’t seem to be that you think he wouldn’t do a good job; it’s that you disapprove of his behavior during the pandemic.As an empirical matter, though, there’s reason to doubt that people’s character traits are “global” — that the careful accountant is a careful driver, that the faithless spouse is a disloyal friend, that the effective product manager will share your sensible concerns about unnecessary travel and socializing. So yes, that’s a big logical leap.Still, you’re entitled to decline to recommend him because you think that he failed to display a concern for the common good; as an ethical matter, you can deny a favor to someone who, in your view, lacks an important virtue. What you can’t do is say you’ll recommend him and then not do so.I’m in a high-risk group, eligible for a Covid vaccination in both the state I live in and a neighboring state. My state is doing a poor job of distributing vaccines, and I’ve failed to get an appointment. But the neighboring state has a terrific system. A friend who lives there got me an appointment. I know that they don’t ask for your address when you arrive for your appointment, which suggests that they’re not overly concerned about residency, and my friend didn’t misrepresent me when signing me up. Am I right to feel a twinge of guilt all the same? Name WithheldDifferent states have different approaches. Our collective goal, as a nation, is to get as many people vaccinated — especially those at particular risk — as quickly as we can. But because states are allocated vaccines on the basis of their population, some are taking a firm line, restricting vaccinations to those who live or work there; they may require documentation or at least self-attestation to this effect. Other state officials seem OK with letting visitors in the line. So long as you don’t misrepresent yourself at any point, you can proceed with an easy conscience.Kwame Anthony Appiah teaches philosophy at N.Y.U. His books include “Cosmopolitanism,” “The Honor Code” and “The Lies That Bind: Rethinking Identity.” To submit a query: Send an email to ethicist@nytimes.com; or send mail to The Ethicist, The New York Times Magazine, 620 Eighth Avenue, New York, N.Y. 10018. (Include a daytime phone number.)

Researchers are exploring the possible benefits of pairing doses from two different Covid-19 vaccines.In January, Britain made a change to its vaccine guidelines that shocked many health experts: If the second dose of one vaccine wasn’t available, patients could be given a different one.The new rule was based on sheer guesswork; there was no scientific data at the time demonstrating that mixing two coronavirus vaccines was safe and effective. But that may change soon.In February, researchers at the University of Oxford began a trial in which volunteers received a dose of the Pfizer-BioNTech vaccine followed by a dose of AstraZeneca’s formulation, or vice versa. This month, the researchers will start analyzing the blood of the subjects to see how well the mix-and-match approach works.As growing numbers of vaccines are being authorized, researchers are testing other combinations. A few are in clinical trials, while others are being tested in animals for now.Mixing vaccines might do more than just help overcome supply bottlenecks. Some researchers suspect that a pair of different vaccines might work better than two doses of the same one.“I think we’re on the cusp of some interesting data,” said Adam Wheatley, an immunologist at the University of Melbourne in Australia.The concept of mixing vaccines — sometimes called a heterologous prime-boost — is not new to our pandemic era. For decades, researchers have investigated the approach, hoping to find potent combinations against a range of viruses, such as influenza, H.I.V. and Ebola.But scientists had little to show for all that research. It was easy enough to demonstrate that two vaccines may work well together in a mouse. But running full-blown clinical trials on a combination of vaccines is a tall order.“For a single company to develop two parallel arms of a vaccine is twice the work and twice the cost,” Dr. Wheatley said.Some of the early successes for heterologous prime-boosts came in the search for vaccines for Ebola. Many researchers focused their efforts on presenting the immune system with a protein found on the surface of the Ebola virus.The gene for that protein was inserted into a different, harmless virus. When people received an injection of the vaccine, the harmless virus entered their cells; the cells then read the instructions in the Ebola gene and mass-produced Ebola’s surface protein. The immune system encountered the Ebola protein and made antibodies against it. And those antibodies protected the vaccinated people if they became infected with a full-blown Ebola virus.This type of vaccine, called a viral vector vaccine, came with a big risk: The recipients might develop immunity to the viral vector after just the first dose. When the second dose arrived, their immune systems could swiftly wipe out the viral vector before it delivered its payload.A number of vaccine makers decided to sidestep this potential threat by using different viruses for each dose. That way, the viral vectors in the second dose would be as new to the immune system as the first was. In 2017, for example, researchers at the Gamaleya Research Institute in Russia created an Ebola vaccine whose first dose contained a virus called an adenovirus. The second shot used another virus, called vesicular stomatitis virus.When the Covid-19 pandemic began last year, the Gamaleya researchers used a similar strategy to create vaccines against the new coronavirus. The first dose used the same adenovirus as in their Ebola vaccine, called Ad5. The second dose contained a different human adenovirus, Ad26. The researches inserted a gene into both viruses for the protein on the surface of the coronavirus, called spike.Studies revealed that the vaccine, now known as Sputnik V, provided a strong defense against Covid-19. In clinical trials, the researchers found that it had an efficacy of 91.6 percent. Sputnik V is now in use in Russia and 56 other countries.Recently, the Gamaleya institute joined forces with AstraZeneca, which makes its own Covid-19 vaccine. AstraZeneca’s consists of two doses of a chimpanzee adenovirus called ChAdOx1. Last week, the company reported that its vaccine had an efficacy of 76 percent.The Gamaleya and AstraZeneca teams want to see how well their vaccines work together. They have registered a pair of clinical trials in which volunteers will receive a dose of AstraZeneca’s ChAdOx1 and another of Sputnik V’s Ad26.A spokesman for AstraZeneca said that one trial in Azerbaijan is underway, and a second, in Russia, is still under review by the country’s ministry of health.Dr. Jakob Cramer, the head of clinical development at CEPI, a vaccine development organization, said that vaccines using viral vectors were not the only kind that might benefit from mixing. In fact, certain combinations might provoke a different, more effective immune response than a single type of vaccine. “Immunologically, there are several arguments in favor of exploring heterologous priming,” Dr. Kramer said.Another kind of Covid-19 vaccine being tested contains the actual spike protein, rather than genetic instructions for it. Some of the vaccines contain the entire protein; others contain just a fragment of it. Currently, there are 29 protein-based vaccines for Covid-19 in clinical trials, although none have been authorized yet.Dr. Wheatley and his colleagues have been testing protein-based vaccines in mice. They injected the full spike protein into the animals as a first dose. For the second dose, they injected only the tip of the spike, a region known as the receptor-binding domain, or R.B.D.Dr. Wheatley and his colleagues found that the mixture worked better than two doses of the spike or of the R.B.D.The researchers suspect that the first dose produces a broad range of antibodies that can stick to spots along the length of the spike protein, and that the second dose delivers a big supply of particularly potent antibodies to the tip of the spike. Together, the assortment of antibodies does a better job of stopping the coronavirus.“You’re able to basically take that initial immunity that was elicited to that spike vaccine, and then really focus it down onto that R.B.D.,” Dr. Wheatley said.Other combinations of vaccines may bring benefits of their own. Some vaccines, especially protein-based ones, do a good job of generating antibodies. Others, such as viral vectors, are better at training immune cells. A viral vector followed by a protein boost might offer the best of both worlds.John Moore, a virologist at Weill Cornell Medicine, cautioned that there was no guarantee that clinical trials would reveal a benefit to mixing vaccines. In the search for an H.I.V. vaccine, researchers tried combining viral vectors and protein boost without success, he noted. Still, Dr. Moore said, the story might turn out differently for coronavirus vaccines.“I’d like to see these studies done,” he said. “Doing it in the Covid space is completely rational, but may not be necessary.”Some researchers are investigating heterologous vaccines not to find a superior mixture, but simply to open up more options for countries desperate to vaccinate their populations. Last week, India held back exports of vaccines to other countries as it grappled with a surge of Covid-19. For countries that were counting on those vaccines, a safe alternative for second doses could save lives.After Britain was criticized in January for suggesting that vaccines could be mixed, researchers at the University of Oxford set out to put the idea to a formal test. In a trial called Com-Cov, they recruited 830 volunteers to test the two vaccines authorized by the British government: AstraZeneca’s adenovirus-based vaccine and the vaccine by Pfizer-BioNTech.Pfizer-BioNTech’s vaccine uses a fundamentally different technology to produce spike proteins in the body. It contains tiny bubbles with genetic molecules called RNA. Once the bubbles fuse to cells, the cells use the RNA to make spike proteins.One group of volunteers is receiving a Pfizer-BioNTech shot followed by AstraZeneca, while another will receive them in the reverse order. The other volunteers are receiving the standard two-dose version of the vaccines.Later this month, the Oxford team will draw blood from the volunteers, examining their antibodies and immune cells to see whether the heterologous prime-boost creates an immune response roughly as strong as two doses of each of the authorized vaccines.If more vaccines are authorized in Britain, the Com-Cov team may add them to the trial. Dr. Matthew Snape, who is leading the Com-COV trial, hopes it will be useful not just to his own country but to others that will be trying to vaccinate their citizens over the next few years.“It might be that actually this flexibility becomes essential in the future,” he said.Dr. Cramer said CEPI is planning to support additional heterologous prime-boost studies. There are plenty of possible studies to run. Worldwide, 13 vaccines are now in use against Covid-19, with 67 more in clinical trials.“In the current situation, we have a quite a luxurious position of having so many advanced, effective vaccines,” Dr. Wheatley said.As the number of authorized vaccines grows, the possible combinations in which they can be used will explode. Recently, researchers at China’s National Institutes for Food and Drug Control scaled up their research on heterologous prime-boosts by trying out four different vaccines that have either been authorized in China or are in late-stage clinical trials there — vaccines based on adenoviruses, proteins, RNA and coronaviruses that have been inactivated with chemicals.The researchers injected mice with a first dose of one vaccine, then a second dose of another. Some of the combinations caused the mice to produce stronger immune responses than mice that received the same vaccine for both doses.Whether scientists carry out more experiments on other vaccines will depend on the willingness of the vaccine manufacturers. “You’re requiring quite large pharmaceutical companies to play nice together,” Dr. Wheatley said.Dr. Bernard Moss, a virologist at the National Institute of Allergy and Infectious Diseases, suspects that a number of companies will be willing to let their vaccines be tested in combinations. “It’s always better to be a part of something that is going to be used,” he said, “than to wholly own something that isn’t.”

Researchers are exploring the possible benefits of combining doses from two different Covid-19 vaccines.In January, Britain made a change to its vaccine guidelines that shocked many health experts: If the second dose of one vaccine wasn’t available, patients could be given a different one.The new rule was based on sheer guesswork; there was no scientific data at the time demonstrating that mixing two coronavirus vaccines was safe and effective. But that may change soon.In February, researchers at the University of Oxford began a trial in which volunteers received a dose of the Pfizer-BioNTech vaccine followed by a dose of AstraZeneca’s formulation, or vice versa. This month, the researchers will start analyzing the blood of the subjects to see how well the mix-and-match approach works.As a growing number of vaccines are being authorized, researchers are testing other combinations. A few are in clinical trials, while others are being tested in animals for now.Mixing vaccines might do more than just help overcome supply bottlenecks. Some researchers suspect that a pair of different vaccines might work better than two doses of the same one.“I think we’re on the cusp of some interesting data,” said Adam Wheatley, an immunologist at the University of Melbourne in Australia.The concept of mixing vaccines — sometimes called a heterologous prime-boost — is not new to our pandemic era. For decades, researchers have investigated the approach, hoping to find potent combinations against a range of viruses, such as influenza, H.I.V. and Ebola.But scientists had little to show for all that research. It was easy enough to demonstrate that two vaccines may work well together in a mouse. But running full-blown clinical trials on a combination of vaccines is a tall order.“For a single company to develop two parallel arms of a vaccine is twice the work and twice the cost,” Dr. Wheatley said.Some of the early successes for heterologous prime-boosts came in the search for vaccines for Ebola. Many researchers focused their efforts on presenting the immune system with a protein found on the surface of the Ebola virus.The gene for that protein was inserted into a different, harmless virus. When people received an injection of the vaccine, the harmless virus entered their cells; the cells then read the instructions in the Ebola gene and mass-produced Ebola’s surface protein. The immune system encountered the Ebola protein and made antibodies against it. And those antibodies protected the vaccinated people if they became infected with a full-blown Ebola virus.This type of vaccine, called a viral vector vaccine, came with a big risk: The recipients might develop immunity to the viral vector after just the first dose. When the second dose arrived, their immune systems could swiftly wipe out the viral vector before it delivered its payload.A number of vaccine makers decided to sidestep this potential threat by using different viruses for each dose. That way, the viral vectors in the second dose would be as new to the immune system as the first was. In 2017, for example, researchers at the Gamaleya Research Institute in Russia created an Ebola vaccine whose first dose contained a virus called an adenovirus. The second shot used another virus, called vesicular stomatitis virus.When the Covid-19 pandemic began last year, the Gamaleya researchers used a similar strategy to create vaccines against the new coronavirus. The first dose used the same adenovirus as in their Ebola vaccine, called Ad5. The second dose contained a different human adenovirus, Ad26. The researches inserted a gene into both viruses for the protein on the surface of the coronavirus, called spike.Studies revealed that the vaccine, now known as Sputnik V, provided a strong defense against Covid-19. In clinical trials, the researchers found that it had an efficacy of 91.6 percent. Sputnik V is now in use in Russia and 56 other countries.Recently, the Gamaleya institute joined forces with AstraZeneca, which makes its own Covid-19 vaccine. AstraZeneca’s consists of two doses of a chimpanzee adenovirus called ChAdOx1. Last week, the company reported that its vaccine had an efficacy of 76 percent.The Gamaleya and AstraZeneca teams want to see how well their vaccines work together. They have registered a pair of clinical trials in which volunteers will receive a dose of AstraZeneca’s ChAdOx1 and another of Sputnik V’s Ad26.A spokesman for AstraZeneca said that one trial in Azerbaijan is underway, and a second, in Russia, is still under review by the country’s ministry of health.Dr. Jakob Cramer, the head of clinical development at CEPI, a vaccine development organization, said that vaccines using viral vectors were not the only kind that might benefit from mixing. In fact, certain combinations might provoke a different, more effective immune response than a single type of vaccine. “Immunologically, there are several arguments in favor of exploring heterologous priming,” Dr. Kramer said.Another kind of Covid-19 vaccine being tested contains the actual spike protein, rather than genetic instructions for it. Some of the vaccines contain the entire protein; others contain just a fragment of it. Currently, there are 29 protein-based vaccines for Covid-19 in clinical trials, although none have been authorized yet.Dr. Wheatley and his colleagues have been testing protein-based vaccines in mice. They injected the full spike protein into the animals as a first dose. For the second dose, they injected only the tip of the spike, a region known as the receptor-binding domain, or R.B.D.Dr. Wheatley and his colleagues found that the mixture worked better than two doses of the spike or of the R.B.D.The researchers suspect that the first dose produces a broad range of antibodies that can stick to spots along the length of the spike protein, and that the second dose delivers a big supply of particularly potent antibodies to the tip of the spike. Together, the assortment of antibodies does a better job of stopping the coronavirus.“You’re able to basically take that initial immunity that was elicited to that spike vaccine, and then really focus it down onto that R.B.D.,” Dr. Wheatley said.Other combinations of vaccines may bring benefits of their own. Some vaccines, especially protein-based ones, do a good job of generating antibodies. Others, such as viral vectors, are better at training immune cells. A viral vector followed by a protein boost might offer the best of both worlds.John Moore, a virologist at Weill Cornell Medicine, cautioned that there was no guarantee that clinical trials would reveal a benefit to mixing vaccines. In the search for an H.I.V. vaccine, researchers tried combining viral vectors and protein boost without success, he noted. Still, Dr. Moore said, the story might turn out differently for coronavirus vaccines.“I’d like to see these studies done,” he said. “Doing it in the Covid space is completely rational, but may not be necessary.”Some researchers are investigating heterologous vaccines not to find a superior mixture, but simply to open up more options for countries desperate to vaccinate their populations. Last week, India held back exports of vaccines to other countries as it grappled with a surge of Covid-19. For countries that were counting on those vaccines, a safe alternative for second doses could save lives.After Britain was criticized in January for suggesting that vaccines could be mixed, researchers at the University of Oxford set out to put the idea to a formal test. In a trial called Com-Cov, they recruited 830 volunteers to test the two vaccines authorized by the British government: AstraZeneca’s adenovirus-based vaccine and the vaccine by Pfizer-BioNTech.Pfizer-BioNTech’s vaccine uses a fundamentally different technology to produce spike proteins in the body. It contains tiny bubbles with genetic molecules called RNA. Once the bubbles fuse to cells, the cells use the RNA to make spike proteins.One group of volunteers is receiving a Pfizer-BioNTech shot followed by AstraZeneca, while another will receive them in the reverse order. The other volunteers are receiving the standard two-dose version of the vaccines.Later this month, the Oxford team will draw blood from the volunteers, examining their antibodies and immune cells to see whether the heterologous prime-boost creates an immune response roughly as strong as two doses of each of the authorized vaccines.If more vaccines are authorized in Britain, the Com-Cov team may add them to the trial. Dr. Matthew Snape, who is leading the Com-COV trial, hopes it will be useful not just to his own country but to others that will be trying to vaccinate their citizens over the next few years.“It might be that actually this flexibility becomes essential in the future,” he said.Dr. Cramer said CEPI is planning to support additional heterologous prime-boost studies. There are plenty of possible studies to run. Worldwide, 13 vaccines are now in use against Covid-19, with 67 more in clinical trials.“In the current situation, we have a quite a luxurious position of having so many advanced, effective vaccines,” Dr. Wheatley said.As the number of authorized vaccines grows, the possible combinations in which they can be used will explode. Recently, researchers at China’s National Institutes for Food and Drug Control scaled up their research on heterologous prime-boosts by trying out four different vaccines that have either been authorized in China or are in late-stage clinical trials there — vaccines based on adenoviruses, proteins, RNA and coronaviruses that have been inactivated with chemicals.The researchers injected mice with a first dose of one vaccine, then a second dose of another. Some of the combinations caused the mice to produce stronger immune responses than mice that received the same vaccine for both doses.Whether scientists carry out more experiments on other vaccines will depend on the willingness of the vaccine manufacturers. “You’re requiring quite large pharmaceutical companies to play nice together,” Dr. Wheatley said.Dr. Bernard Moss, a virologist at the National Institute of Allergy and Infectious Diseases, suspects that a number of companies will be willing to let their vaccines be tested in combinations. “It’s always better to be a part of something that is going to be used,” he said, “than to wholly own something that isn’t.”

More than just a sign of illness, mucus is a critical part of our body’s defenses against disease. Every day, our bodies produce more than a liter of the slippery substance, covering a surface area of more than 400 square meters to trap and disarm microbial invaders.
Mucus is made from mucins — proteins that are decorated with sugar molecules. Many scientists are trying to create synthetic versions of mucins in hopes of replicating their beneficial traits. In a new study, researchers from MIT have now generated synthetic mucins with a polymer backbone that more accurately mimic the structure and function of naturally occurring mucins. The team also showed that these synthetic mucins could effectively neutralize the bacterial toxin that causes cholera.
The findings could help give researchers a better idea of which features of mucins contribute to different functions, especially their antimicrobial functions, says Laura Kiessling, the Novartis Professor of Chemistry at MIT. Replicating those functions in synthetic mucins could eventually lead to new ways to treat or prevent infectious disease, and such materials may be less likely to lead to the kind of resistance that occurs with antibiotics, she says.
“We would really like to understand what features of mucins are important for their activities, and mimic those features so that you could block virulence pathways in microbes,” says Kiessling, who is the senior author of the new study.
Kiessling’s lab worked on this project with Katharina Ribbeck, the Mark Hyman, Jr. Career Development Professor of Biological Engineering, and Richard Schrock, the F.G. Keyes Professor Emeritus of Chemistry, who are also authors of the paper. The lead authors of the paper, which appears today in ACS Central Science, are former MIT graduate student Austin Kruger and MIT postdoc Spencer Brucks.
Inspired by mucus
Kiessling and Ribbeck joined forces to try to create mucus-inspired materials in 2018, with funding from a Professor Amar G. Bose Research Grant. The primary building blocks of mucus are mucins — long, bottlebrush-like proteins with many sugar molecules called glycans attached. Ribbeck has discovered that these mucins disrupt many key functions of infectious bacteria, including their ability to secrete toxins, communicate with each other, and attach to cellular surfaces.

Mount Sinai researchers have found that a widely available and inexpensive drug targeting inflammatory genes has reduced morbidity and mortality in mice infected with SARS-CoV-2, the virus that causes COVID-19. In a study published today in the journal Cell, the team reported that the drug, Topotecan (TPT), inhibited the expression of inflammatory genes in the lungs of mice as late as four days after infection, a finding with potential implications for treatment of humans.
“So far, in pre-clinical models of SARS-CoV-2, there are no therapies — either antiviral, antibody, or plasma — shown to reduce the SARS-CoV-2 disease burden when administered after more than one day post-infection,” says senior author Ivan Marazzi, PhD, Associate Professor of Microbiology at the Icahn School of Medicine at Mount Sinai. “This is a huge problem because people who have severe COVID19 and get hospitalized, often do not present symptoms until many days after infection. We took a different approach, and sought to find a potential therapy that can be used during later stages of the disease. We found that the TOP1 inhibitors given days after the infection can still limit the expression of hyper-inflammatory genes in the lungs of infected animals and improve infection outcomes.” Moreover, says Dr. Marazzi, topotecan (TPT), an FDA-approved Topoisomerase I (TOP1) inhibitor, as well as its derivatives, are inexpensive clinical-grade inhibitors available in most countries around the world for use as antibiotic and anti-cancer agents.
Although the pathophysiology of SARS-CoV-2 is not yet fully understood, scientists have observed that the virus triggers excess production of cytokines and chemokines — chemicals which are secreted by cells of the immune system to help fight infection. An exaggerated immune system response, which characteristically occurs in the lungs of COVID-19 patients, can flood the infected area with white blood cells, resulting in inflammation, possible tissue damage, organ failure, and death. Reduction of the inflammatory state in such patients could therefore improve their clinical outcomes.
In a previous study published in Science in 2016, the same group at Mount Sinai found that inhibiting the activation of inflammatory genes could help prevent animal deaths from viral and bacterial infections and suggested this could be a potent strategy against future pandemics. The current study, led by Mount Sinai along with partners from Singapore, Hong Kong, the United Kingdom, the United States, and other global sites, expands on that earlier work to show how epigenetic therapy (which addresses the chemical modifications that influence gene expression) could be harnessed against severe cases of COVID-19.
The team’s research suggests that many other anti-inflammatory agents are less effective against COVID-19 because they target only a single inflammatory mediators, such as IL6 or IL1, or a specific gene expression program. “The fact is, a multitude of inflammatory genes and signaling pathways are dysregulated during a SARS-CoV-2 infection,” explained lead author Jessica Sook Yuin Ho, PhD, a postdoctoral researcher at Icahn Mount Sinai. “We demonstrated that TOP1 inhibitors were able to broadly or systemically dampen inflammatory gene expression in animal models, regardless of the gene or activation pathway.”
Co-author Mikhail Spivakov, PhD, head of the Functional Gene Control group at the MRC London Institute of Medical Sciences added, “We found that infection prompts extensive changes in the 3D connections between inflammatory genes and the ‘molecular switch’ regions that control their expression. This may partially explain why inhibiting topoisomerase, a protein that helps reshape DNA, helps dampen the cells’ hyper-inflammatory response.”
The safety and efficacy of this treatment strategy in humans will soon be evaluated at clinical sites around the world, including India, where a trial recently began and Singapore, where the National Medical Research Council of Singapore has also funded a phase 1 clinical trial of topoisomerase 1 inhibition in COVID-19. The World Health Organization (WHO) is also expected to play an important role in subsequent studies.
“Findings from our work suggest that repurposing the TOP1 inhibitor could be a valuable global strategy for treating severe cases of COVID-19,” emphasizes Dr. Marazzi. “Particularly attractive is the fact that TPT is already FDA-approved and that its derivatives are inexpensive, with generic formulations existing throughout the world. This makes these drugs readily accessible and available for immediate use in both developing and developed countries across the world.”

After more than three decades of research, scientists have proven that the cancer affecting up to one in four adult California sea lions necrospied at The Marine Mammal Center in Sausalito, CA, is caused by a sexually transmitted herpesvirus. The cancer, known as sea lion urogenital carcinoma, has clear parallels to cervical cancer in humans and provides a helpful model for human cancer study.
Scientists have long suspected this cancer was associated with a virus, but this is the first study to prove this theory. The study, which was published in Animals, an open-access, peer-reviewed journal, concluded that genital herpesvirus is a driving factor in the development of sea lion urogenital carcinoma. The research also suggests there is an underlying trigger or event that causes the virus to induce cancer in some infected sea lions and not others. Wild California sea lions have among the highest prevalence of a single type of cancer in any mammal, including humans.
A second recently published paper (Sea lions are dying from a mysterious cancer. — Los Angeles Times) led by the same team showed that pollutants such as PCBs and DDT play a significant role as co-factors in the development of this cancer. This is particularly relevant to Southern California where there is a large DDT dumpsite in the Southern California bight which is also where the majority of the sea lion population gather each year to give birth and raise their pups (How the waters off Catalina became a DDT dumping ground — Los Angeles Times).
“The confirmation that this is a virally induced cancer combined with the knowledge that contaminants play a significant role in the cancer’s development means that we can use these sea lions as a naturally occurring disease model to better understand how cancer develops and spreads in all species, including humans,” says Dr. Alissa Deming, the lead author of the study who completed this work during her Ph.D. studies at University of Florida in Gainesville, FL., while she was a Research Fellow at The Marine Mammal Center in Sausalito, CA. (Dr. Deming is now Director of Clinical Medicine at the Pacific Marine Mammal Center in Laguna Beach, CA.)
The Marine Mammal Center is the world’s largest marine mammal hospital and has been on the forefront of researching and understanding cancer in California sea lions and its connection to both ocean and human health. Since cancer in sea lions was first discovered in 1979, researchers have found that between 18-23 percent of adult sea lions admitted to the Center’s hospital have died of the fatal disease. In 2010, the Center brought together an array of international researchers to form the Sea Lion Cancer Consortium to further investigate this disease, many of whom helped co-author the paper.
“This research is critical as these sea lions may hold the key to understanding virally induced cancers as well as how cancer metastasizes, or spreads through the body,” says Dr. Pádraig Duignan, Director of Pathology at The Marine Mammal Center and a co-author on the study. “This knowledge is an important link that could help scientists better understand various cancers in people.” Most cancers are caused by an accumulation of several factors, making it challenging to study cancer in traditional laboratory models. However, wild sea lions experience multiple layers of stressors including infectious agents, exposure to pollutants, nutrition, and environmental influences, all of which are much more representative of how cancer develops in the “real world.”
According to Duignan, “the cancer begins in the sea lion’s genital tract and aggressively spreads throughout the sea lion’s body, resulting in death, often from kidney failure.” Because of the advanced state of cancer by the time these patients strand on beaches and are rescued by rehabilitation centers, euthanasia is the only humane option. “This cancer is devastating to see in California sea lions. They come to the hospital in end-stage disease,” says Dr. Deming.
The paper was the result of an international, cross-discipline effort, combining multiple techniques from a variety of specialists to unlock the mysteries of this disease. The research relied on novel techniques using RNAscope® Technology and Base Scope™, tools that allow researchers to pinpoint high viral gene expression within tumor tissue but not in surrounding healthy tissue.
“Our study was the first time that this revolutionary technique has been used on a marine mammal species,” says Dr. Kathleen Colegrove, Clinical Professor of the Zoological Pathology Program at the University of Illinois Urbana-Champaign, and a key researcher on the study. “This proved that the virus was integral to cancer development and was not just being detected in the reproductive tracts or tissue as a bystander.”
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Materials provided by The Marine Mammal Center. Note: Content may be edited for style and length.