Combination Nanoparticle Therapy Shows Promise as Antiviral

Researchers have developed a new nanoparticle combination as a broad-spectrum anti-RNA virus treatment. 

The results of their study have been published on the bioRxiv preprint server. Note that as a preprint, this paper has not yet been peer reviewed.
Non-specific antivirals offer a number of attractive advantages. Their broad spectrum activity suppresses mutations, and would they also readily be at hand for future outbreaks. Nanoparticles are one possibility, with reduced toxicity.

Silver nanoparticles (AgNPs) are well-established as antibacterial and antiviral agents, and are the subject of many exotic biomedical applications. The mechanism of AgNPs is thought to be through physiochemical destruction of the microbial surface, with internal disruption from free Ag+ ions and reactive oxide species. Graphene oxide (GO) also has anti microbial properties. With its high surface area, GO also acts as a drug carrier.

The researchers produced seven different material combinations using three different methods: reduction with silver salt, direct addition of Ag nanospheres, and direct addition of Ag nanospheres to thiolised graphene.
To test the materials against seasonal-type infections as well as the kind of virus that could be expected from a future pandemic, the researchers tested the nanoparticles with influenza A virus (IAV) and human coronavirus (HCoV) OC43. IAV is an enveloped virus of the orthomyxovirus family with a segmented single-stranded RNA genome; it causes flu pandemics. HCoV-OC43 is an enveloped betacoronavirus with a single-stranded RNA genome associated with the common cold in humans.

Two of the GO-AgNP materials showed rapid, potent antiviral activity in solution against the viruses. The remaining five materials possessed a range of modest to no antiviral effects against IAV, the researchers reported. They observed a synergistic effect between the AgNPs and GO, with mechanism of action possibly being rapid disruption of the viral envelope. With high levels of antiviral agents, the combination of AgNPs with GO was found to show greater antiviral performance and lower toxicity.

“Our finding that graphene oxide/silver nanoparticle ink can rapidly prevent in vitro infection with two different viruses is exciting, and suggests that the ink has the potential to be used in a variety of applications to help reduce the spread of viruses in the environment,” said co-author Dr Meredith J Crane.

Source: News-Medical.Net

Journal information: Graphene oxide/silver nanoparticle ink formulations rapidly inhibit influenza A virus and OC43 coronavirus infection in vitro, Meredith J. Crane, Stephen Devine, Amanda M. Jamieson, bioRxiv 2021.02.25.43

Rollout of Peanut Allergy Treatment Stalled by Pandemic

Approved in late January 2020, the only FDA-approved peanut immunotherapy was due to be released onto the US market, but the arrival of the pandemic effectively shut it down.

The peanut-powder Palforzia allergen treatment is designed to desensitise peanut allergies in children and adolescents, and circumvent potentially life-threatening reactions.

It is unclear to what extent peanut allergy immunotherapy (IT) and other forms of IT will be embraced by the US public. While subcutaneous IT has been practised for a long time, oral IT such as sublingual IT tablets are relatively new, with only a few products currently having regulatory approval in the US and Europe.

However, there are questions as to whether the US will ever widely accept IT, given factors such as the high treatment burden. Speaking to MedPage Today, Edwin Kim, MD, director of the University of North Carolina Food Allergy Initiative in Chapel Hill, said that it may not be clear for a while to what extent the treatment is accepted.

“COVID-19 shined a spotlight on the downsides of a treatment that requires so many physician visits,” he said. “If it was an easy treatment we might have seen more uptake, but it’s not an easy treatment.”

Thomas Casale, MD, of the University of South Florida in Tampa, acknowledged to MedPage Today that Palforzia’s uptake in the past year has been slow as “A treatment like this requires a lot of contact with the patient.”

The dosing schedule involves around a dozen physician visits, of 30-90 minutes duration each.  A single-day initial dose escalation phase is needed, with up-dosing every two weeks with physician observation to attain 11 increasing dose levels. After this, there is a daily home-dosing maintenance phase.

The 300-mg peanut protein maintenance dose is equivalent to eating a single peanut. “If you are able to tolerate 300 mg of peanut you can effectively prevent about 95% of adverse reactions,” Casale said. “So 300 mg is an important indicator of some degree of safety.”
In pooled trial data on Palforzia presented by Dr Casale, only 1.2% of long-term patients had a treatment-related severe systemic allergic reaction, all of which were treated with epinephrine.

“I think that after COVID is gone, which hopefully will be sooner than later, the uptake of this type of therapy will be a lot greater than it is today,” Dr Casale said.

Viaskin Peanut, an extracutaneous peanut IT, is undergoing investigational trials, with the FDA rejecting application for its approval. The agency cited concerns about the impact of patch-site adhesion on efficacy, and demanded modifications and additional trials.

Christina Ciaccio, MD, chief of allergy/immunology and pediatric pulmonology and sleep medicine at the University of Chicago, said that there were many challenges remaining.

“We have numerous forms of immunotherapy that are currently under investigation,” she said. “The fact that only one allergen-specific IT treatment for food allergy has been approved by the FDA highlights the remaining challenges.”

“For those that do have peanut allergies, this treatment [IT] is not universally effective and it is not universally available,” Ciaccio said. “The side effects are too frequent, and as it stands right now, this is a life-long therapy. These are all things we would like to work on.”

Source: MedPage Today

Bacteria in Cystic Fibrosis Use Slimy Shield to Ward off Drugs

Research has revealed that a common bacteria found in the lungs of those with cystic fibrosis produces a slime that acts as a defence against a variety of therapeutic drugs.

Dr Laura Jennings, a research assistant professor in UM’s Division of Biological Sciences and an affiliate with the University’s Center for Translational Medicine, headed the research.

A life threatening-condition caused by a genetic mutation, cystic fibrosis causes persistent lung infections and gradually reduces a person’s breathing capacity. A common strain of bacteria, Pseudomonas aeruginosa, often thrives in the lungs of people with cystic fibrosis,  and when a P. aeruginosa infection is established, it can be extremely hard to remove.
The research showed that stubborn bacteria dwelling in the lungs of cystic fibrosis patients produce a carbohydrate slime, which both shields them against antibiotics and also mucus-reducing drugs.

“We found the first direct evidence that these carbohydrates are produced at the sites of infection,” Dr Jennings said. “We showed that one of the carbohydrates, called Pel, sticks to extracellular DNA, which is abundant in the thick mucus secretions prominent in cystic fibrosis lungs.

“This interaction makes a slimy protective layer around the bacteria, making them harder to kill,” she said. “As such, it reduces the pathogen’s susceptibility to antibiotics and drugs aimed at reducing the thickness of airway mucus by digesting DNA.”

She explained that the research supports a theory that these carbohydrates also support the aggregation of these bacteria in the lungs of cystic fibrosis patients.

“This is important because we know that physically breaking up bacterial aggregates can restore bacterial susceptibility to killing with antibiotics and cells of the immune system,” Jennings said. “Therefore, understanding the mechanisms that promote bacterial aggregation may facilitate new therapeutic approaches aimed at digesting the carbohydrates holding bacterial cells together.”

Source: Medical Xpress

Journal information: Laura K. Jennings et al. Pseudomonas aeruginosa aggregates in cystic fibrosis sputum produce exopolysaccharides that likely impede current therapies, Cell Reports (2021). DOI: 10.1016/j.celrep.2021.108782

Only Smaller ‘Good’ Cholesterol Particles Reduce Heart Risk

New research on cholesterol shows that ‘good cholesterol’ is not all good for the heart – only smaller particles reduce heart risk.

Higher levels of ‘good cholesterol’ or high-density lipoprotein cholesterol (HDL-c ) have been associated with better cardiovascular outcomes. In contrast, ‘bad cholesterol’ or low-density lipoprotein cholesterol (LDL-c ), deposits cholesterol on artery walls, increasing the risk of cardiovascular disease.

Medications that lowers LDL-c  also reduce cardiovascular risk, but medication that increases HDL-c does not decrease cardiovascular risk. This paradox calls into question the assumption that HDL-c is protective against cardiovascular risk.

Researchers analysed the size of HDL-c particles, which is determined by genetic characteristics, and compared this to the risk of myocardial infarction. The results showed that genetic characteristics for having large HDL-c particles were associated with increased heart attack risk. Characteristics for smaller HDL-c particles were linked to reduced heart attack risk.

“There is a positive causal relationship between the size of HDL cholesterol particles and the risk of heart attack, so although we have to increase the levels of good cholesterol in the blood, they must always be small particles,” explains the study’s principal investigator, Dr Robert Elosua, a researcher at the Hospital del Mar-IMIM, CIBERCV, and the University of Vic-Central University of Catalonia.

The HDL-c particles are more effective in transferring cholesterol to the liver for subsequent elimination. “If we need to do something in relation to HDL, it is to increase the number of small particles, which are those that adequately perform the function of eliminating cholesterol, those that really move it to the liver for removal, and do not allow it to accumulate in the arteries and cause cardiovascular disease,” said Dr Álvaro Hernáez.
There are currently no drugs that increase HDL-c and also reduce cardiovascular risk. “This study highlights new and potential therapeutic targets in the field of cardiovascular diseases, including several genes related to the qualitative aspects of HDL particles, which may contribute to cardiovascular prevention,” concluded first author Dr Albert Prats.

Source: Medical Xpress

Journal information: Albert Prats-Uribe et al, High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study, Metabolism (2020). DOI: 10.1016/j.metabol.2020.154351

US Rollout of Johnson & Johnson Vaccine As It Gets FDA Approval

Johnson & Johnson’s single shot COVID vaccine is set to roll out in the US after its approval, but concerns linger as to the public’s perception of its relative effectiveness.

The vaccine received an emergency use authorisation (EUA) on Saturday from the FDA, and received approval from the CDC the following day. On Sunday night White House officials stated that distribution of 3.9 million doses of the J&J vaccine would begin immediately, with J&J expecting to deliver some 16 million more doses by the end of March. These vaccines will be allocated proportionally, as per the procedure for Pfizer/BioNTech and Moderna vaccines.

At a Saturday media briefing, acting FDA Commissioner Janet Woodcock, MD, reiterated issues raised by the FDA advisory committee, that the J&J product’s lower efficacy number (70% vs 95%) may cause people to think it is less effective than the alternatives. She said that wasn’t necessarily so, urging Americans to “take the vaccine they are able to access.”

“All these vaccines meet our standards for effectiveness. They were not studied in head-to-head trials, so [they’re] difficult to compare … due to differences in development programs,” she said. (Preventing moderate-to-severe COVID illness was the J&J endpoint, whereas in the Pfizer and Moderna studies the endpoint was all symptomatic COVID.)

“We need to be clear on our messaging regarding comparisons with other vaccines,” said Jason Goldman, MD, of the American College of Physicians. “As a primary care physician, many of us are eager to vaccinate” patients and this vaccine will be “helpful in achieving that goal.”

Macaya Douoguih, MD, of J&J’s Janssen unit where the vaccine was developed, talked about the potential advantages of a one-dose vaccine, referencing the company experience with the Ebola vaccine

“For an outbreak setting, a single dose has a tremendous advantage in terms of being able to rapidly roll out mass vaccination” without the complexity of following up for a second dose, she said.

Dr Douoguih addressed the company’s planned two-dose study, saying that while a two-dose regimen might be “more immunogenic and lead to durable efficacy,” she thought there was room for both options. The two-dose option would be preferable in an ‘everyday’ COVID setting. The company was trying to enroll 16-17 year olds for additional data in a study starting next week, Dr Douoguih said.

The CDC researchers discussed preliminary data on asymptomatic infection, which assessed seroconversion between days 29 and 71. Those data showed vaccine efficacy against seroconversion was 74% (95% CI 48%-87%), but the CDC urged caution as the data was only preliminary.

“Our level of confidence in asymptomatic infection is tempered by low numbers and that is important for us to remember,” said Advisory Committee on Immunization Practices committee member Sarah Long, MD, of Drexel University College of Medicine in Philadelphia. “I appreciate the workgroup concluding the confidence is not that high.”

Source: MedPage Today

New Care Review Process Helps Cut Preventable Deaths

At a Los Angeles hospital, a new in-person multidisciplinary rapid mortality review (RMR) process successfully helped identification of critical patient care areas, according to a new study.

This novel approach assisted front-line healthcare workers in understanding key individual- and systems-level issues which increase mortality. The aim is to produce more effective, optimised patient care. Though efforts have been made since the Institute of Medicine’s 1999 report on preventable patient mortality, reducing the number of these deaths has been difficult, and in many cases, elusive.

The study looked at five years of the RMR process that reviewed patient deaths that took place in the 24-bed medical intensive care unit (ICU) at Ronald Reagan University of California Los Angeles (UCLA) Medical Center. Not only immediate concerns were picked up, but also valuable insights into preventable patient deaths.

“Our findings suggest that these short and timely in-person meetings can be a powerful tool for efforts to both improve quality and prevent mortality in the ICU,” said first author Kristin Schwab, MD. “Bringing members of the multidisciplinary care team together for regular face-to-face discussions provided a forum that revealed concerns and solicited tangible ideas for solutions.”

Retrospective case reviews, provider surveys, and structured morbidity and mortality conferences are common tactics, but unlikely to provide an efficient and practical means of reviewing all patient deaths. The RMR process started in 2013 as pilot, using data on a subset of patients who had died in the medical ICU during the week before. The subset gradually increased in size and by 2017, the team tried to review every death that occurred in the unit that week. Over the five-year period, the RMR team reviewed a total 542 deaths, over 80% of all those that occurred in the unit.

For each patient death, a facilitator led a semistructured interview with the care team after reviewing the patient’s chart, and added a brief report to a database. The quality team reviewed the data from each meeting, referring action items to the relevant department.

Only 7% of deaths were determined by the treatment team, RMR facilitator or both to be possibly preventable. However, in more than 40% of the deaths the treatment team thought care could have been improved, while the facilitator identified areas for improvement in over half the cases.

Cases in which the patient required resuscitation after an in-hospital cardiac arrest or those in which the patient did not get comfort care at the time of death were more likely to result in an action item.

Issues included concerns with communication or teamwork, advance care planning, care delays, medical errors, procedural complications and hospital-acquired infections. The systems-related action items were lack of protocols, resource availability and throughput. Among the action items, over 10% led to substantive systemic change, with 29 discrete changes occurring over the study period. Action items included making a standardised checklist for inbound patient transfers, and modifying the electronic health record to separate one-time orders from continuing orders.

Source: News-Medical.Net

Journal information: Schwab, K.E., et al. (2021) Rapid Mortality Review in the Intensive Care Unit: An In-Person, Multidisciplinary Improvement Initiative. American Journal of Critical Care. doi.org/10.4037/ajcc2021829.

Gratitude for Engineer’s ‘Hack’ Website for Vaccination Appointments

Frustrated with the difficulties faced in scheduling a vaccination appointment, a New York software engineer developed a website to make it easier for his fellow New Yorkers to schedule an appointment.

Huge Ma was trying to get a COVID vaccination appointment for his mother. “You had to basically open three tabs, one for each major government vaccine portal, and then refresh all day until you got an appointment,” the 31-year-old told The Guardian. This experience inspired him to create a website, Turbovax, that helped people to book their appointments more easily. After taking a “look under the hood” in January and doing two weeks of coding, he unveiled his website – essentially a bot that trawls relevant New York sites for appointments and shares them on Twitter and on a website.

Almost immediately, the website took off, with one million page views a day, with tens of thousand of people having booked appointments using the bot, Mr Ma estimated. People have even asked him to bring TurboVax to their cities.

“The response has been incredibly overwhelming,” he said. “There’s been so much gratitude. Hundreds, thousands of emails from people who have gotten appointments through TurboVax, which is honestly kind of just mind-blowing, and humbling as well.” 

He was unprepared for the reaction. “I would never have thought that I could have built something that has such tangible impact on other people’s lives.” 

However, running the site is difficult as Mr Ma has to balance this with his day job working at Airbnb, and the Google Docs-based site is buckling under the demand.

“Technically it’s kind of a hack. It’s not built in the way that modern websites are supposed to be built,” said Ma. “These are the shortcuts that we take to put something in the world that we think is useful and I think that’s a trade-off that I would still make.”

Though it is free, Mr Ma accepts donations and has gathered $35 000 so far. TurboVax is one of a number of citizen-led services that have popped up to help Americans deal with the difficulties of vaccine appointment bookings, such as NYC Vaccine List in New York and VaccinateCA in California.

Mr Ma shut down the website over the weekend in protest against a spate of hate crimes targetting Asian Americans, tweeting, “Anti-Asian hate crimes are out of control. I am taking a stand because I fear for my friends and family.” However, local law enforcements said there is no sign that a number of recent assaults against Asian Americans were racially motivated.

Since far more white people have received vaccinations than black or Latino people, Mr Ma said the technology can “help level the playing field”.

“Not everyone has the ability to sit in front of a computer and refresh all day,” he explained. “That said, I know that no system is perfect. This tech can help but it can’t solve other inequities in the system.”

Source: The Guardian

Social Cues Impacts on Human Decision-making in Emergencies

Man at the wheel of a car. Photo by why kei on Unsplash.

A study showed that, when participants in a simulated crash of an autonomous vehicle were told that others had chosen to crash into a wall to save pedestrians, their own willingness to do so went up by two-thirds.

As autonomous vehicles become more commonplace, and the need to program them for safety emerges, a better understanding of how humans react in such situations is needed. Study author Jonathan Gratch, the principal investigator for this project, and a computer scientist at the USC Institute for Creative Technologies, said that current models for humans in life-or-death situations, humans think differently to how they do in reality. There are no moral absolutes, rather ” it is more nuanced”.

Seeking to understand how humans make decisions in life-or-death situations and how to apply them to the programming of autonomous vehicles and robots, researchers presented a modified trolley problem to participants using a modified ‘trolley problem’.

The trolley problem is a classic hypothetical scenario psychologists use to investigate human decision-making. Essentially, it involves the decision to divert a tram to hit one person or to leave it on its track and hit five, and it has a number of variations. In one medical variation of the trolley problem, one person could be killed and their organs harvested to save five terminally ill patients — a choice that is overwhelmingly rejected.  

In three of four simulations presented to them, the participants had to choose whether to tell their autonomous vehicle to hit a wall, risking harm to themselves, or hit five pedestrians. The higher the likelihood of injury to pedestrians, the more likely the participants were to choose hitting the wall and risking self harm. The authors showed that in so doing, people balance the risk of injury to self against the potential of injury to others as a guideline.

In the fourth scenario, a social element was added, where participants were told that their peers had chosen to save the pedestrians. In this case, the proportion of participants electing to save the pedestrian went up from 30% to 50%.

However, Gratch there is a reverse as well: “Technically there are two forces at work. When people realize their peers don’t care, this pulls people down to selfishness. When they realize they care, this pulls them up.”

The researchers showed that using the trolley problem as a basis for decision-making is insufficient, as it fails to capture the complexity of human decision-making. The researchers also concluded that transparency in the programming of autonomous machines was important for the public, as well as human operators assuming control in the event of an emergency.

Source: News-Medical.Net

Journal information: de Melo, C. M., et al. (2021) Risk of Injury in Moral Dilemmas With Autonomous Vehicles. Frontiers in Robotics and AI. doi.org/10.3389/frobt.2020.572529.

SA Medical Aid Schemes May Not Have to Pay for Public’s Vaccines

Medical aid scheme executives have pointed out that the latest budget means that medical aid schemes may no longer need to contribute for the vaccination of the South African population without medical insurance. 

South Africa’s medical insurance schemes had been in discussions on funding at least part of the government’s vaccine rollout for uninsured members of the public.

The R9 billion allocated in the budget may be enough to cover the vaccine costs of the entire country, said executives from the two leading medical aid schemes.

About 7 million people are covered by medical aid schemes, about a quarter of the country’s population. Discovery Health, Medscheme and Momentum together administer some 80% of private sector medical aid plans.

“I think the government is looking at this and saying this is our role,” said Damian McHugh, executive head of sales and marketing at Momentum Health Solutions. He agreed with the idea that the budget figure implied that schemes may not have to help cover vaccinations for non-members, although it did not remove the discussion of subsidies.

McHugh went on to explain that the costs would depend on which vaccines were procured, and schemes would still have to contribute in case booster shots or new vaccination rounds became necessary.

However, given record additions to their reserves last year due to medical services not being taken or postponed, along with not having to contribute to the vaccination of non-members, medical aid schemes stand to reap even greater benefits.

Source: Reuters

Siemens COVID Antigen Test Kit Receives German Approval

Siemens Healthineers announced on Wednesday that their antigen self-test kit, which uses samples from a nasal swab, has received limited special approval from the Federal Office for Drugs and Medical Devices (BfArM) for self-use by laypeople in Germany. The regular conformity assessment procedure for the standardised ‘CE‘ mark was also initiated for personal use by laypeople.

“With the provision of the COVID-19 antigen rapid test for possible use by laypeople in Germany, we are breaking new ground and are thus continuing to fulfill our social responsibility to support a return to normal social life,” said Bernd Ohnesorge, Head of Europe, Middle East, and Africa Regions, Siemens Healthineers

The practicability of the kit was confirmed by a study in which 50 participants without medical training personally carried out the test by following the instructions for use. The test already has a CE mark for use by specialist groups for taking samples in the nose.

“The CLINITEST COVID-19 Antigen Self-Test offers users a high degree of flexibility in performing the test with very good quality results,” said Christoph Pedain, Head of Point of Care Diagnostics at Siemens Healthineers.

Siemens’ COVID-19 Antigen Self-Test takes 15 minutes to give a result, using samples taken from both nostrils using a swab. The swab is then washed out in a reagent, which detaches a specific protein from the surface of the virus. The resulting liquid is dripped into a recess in the test cassette.

The test liquid migrates into the field of view of the cassette within 15 minutes, becoming visible as a line. The position and number of lines indicate as to whether there is a positive or negative test result, or whether there was a problem, necessitating a repeat of the test.

In the instructions, the tester is shown the steps to achieve a test result, including instructions on how to proceed according to the test result. A negative test result does not exempt the user from any local COVID regulations. Currently, the test kit is also available in the UK.

Source: Siemens