COVID-19 convalescent plasma for the treatment of immunocompromised patients

 About The Study: The findings this systematic review and meta-analysis suggest that transfusion of COVID-19 convalescent plasma is associated with mortality benefit for patients who are immunocompromised and have COVID-19. 

Authors: Jonathon W. Senefeld, Ph.D., of the Mayo Clinic in Rochester, Minnesota, is the corresponding author. 

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamanetworkopen.2022.50647)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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https://www.eurekalert.org/news-releases/976243

COVID is changing how we are exposed to household health risks

 COVID-19 is changing household behaviors related to how we are exposed to various household chemicals linked to poor health outcomes. People surveyed earlier in the pandemic were using less personal care products but more household cleaners, eating less fast food and restaurant food but more ultra-processed food. These changes which occurred since the pandemic onset are also linked to pandemic-related traumatic stress, which itself may worsen health outcomes.

Researchers at Columbia University Mailman School of Public Health along with partners from Dartmouth College, as part of the Environmental influences on Child Health Outcomes (ECHO) consortium, analyzed responses to a survey from 1,535 adults in six states. Results are published in the journal PLOS ONE.

Personal care products. Overall, participants reported using fewer personal care products, including hair products (perms or relaxers, hair dye, hair sprays, hair gels) and makeup/body products (nail polish, make-up, perfume, lotion) since the start of the pandemic. Participants who experienced more pandemic-related traumatic stress were more likely to report using fewer hair products and cosmetics. Approximately half of all respondents reported using more liquid soaps (52%) and antibacterial soaps (48%) and 81 percent of respondents reported using more hand sanitizer gels. The use of all three products was associated with pandemic-related traumatic stress symptoms.

Household cleansers. Two-thirds of respondents reported using more antibacterial cleaners and 54 percent reported using more bleach-containing cleaning products—changes made more likely among those experiencing more pandemic-related traumatic stress.

Food-related behaviors. Nearly half (49%) of respondents said they eat more home-cooked meals because of the pandemic. One-third (34%) of respondents reported eating less fast food since the start of the pandemic. Both of these behavior changes were more common among those with more symptoms of pandemic-related traumatic stress. In all, 12 percent reported eating more ultra-processed foods, and 24 percent reported eating less processed foods, with the latter more likely among those with symptoms of pandemic-related traumatic stress.

The Upshot

While the study did not include measurements of environmental exposures, the researchers say that the scientific literature suggests that these behavior changes likely reflect changes in their exposures to environmental chemicals. They also likely reflect changes—both good and bad—to health outcomes linked to these chemicals.

“We can infer that some behaviors like less consumption of fast foods and less use of personal care products might lower exposures to some phthalates and phenols, while greater use of personal and household cleansers may be associated with higher exposure to quaternary ammonium compounds and glycol ethers; and more frequent consumption of ultra-processed food could increase exposure to phthalates and phenols,” says lead author Julie Herbstman, PhD, director of the Columbia Center for Children’s Environmental Health (CCCEH) and professor of environmental health sciences.

Phthalates are linked asthma, attention-deficit hyperactivity disorder, breast cancer, obesity and type II diabetes and neurodevelopmental and behavioral issues. Phenols like BPA are linked to reproductive dysfunction, reduced birth size, cognitive and/or behavior outcomes, asthma, and obesity. Quaternary ammonium compounds are skin irritants and can also lead to asthma exacerbations. Exposure to glycol ethers may also irritate skin, eyes, nose, and throat and may also lead to anemia and/or adverse reproductive outcomes like birth defects.  

A Roadmap to Interventions

The study identifies several factors that make some of these behavior changes more likely, including symptoms of pandemic-related traumatic stress and living in a household where someone tested positive for COVID-19, as well as race/ethnicity. Going forward, the researchers plan to repeat their analysis, adding a biological measure of chemical exposures to assess whether the trends in pandemic-related behavior change reported here do, in fact, result in shifts in exposures measured through biomarkers of internal dose. They also say it is important to continue to monitor pandemic-related behavior change as pandemic severity waxes and wanes.

The researchers say their study could lead to an intervention to reduce exposure to harmful environmental chemicals.

“Interventions and campaigns targeting the reduction of environmental exposures, pandemic-related traumatic stress, as well as those that facilitate behavior change can help improve health outcomes that are indirectly related to the pandemic,” says Herbstman.

The study’s senior authors are Frederica Perera, director of the translational research program at CCCEH and professor of environmental health sciences at Columbia Mailman School of Public Health, and Margaret R. Karagas, professor and chair of epidemiology at the Geisel School of Medicine at Dartmouth. A full list of co-authors is available in the journal article.

Funding for the research was provided by grants from the National Institutes of Heath (U2COD023375, U24OD023382, U24OD023382, U24OD023319, UH3OD023290, UH3OD023275, UH3OD023272, UH3OD023271, UH3OD023313).

The authors declare no conflicts.

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JOURNAL

PLoS ONE

DOI

10.1371/journal.pone.0277679 

METHOD OF RESEARCH

Survey

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Characterizing changes in behaviors associated with chemical exposures during the COVID-19 pandemic

ARTICLE PUBLICATION DATE

13-Jan-2023

https://www.eurekalert.org/news-releases/976859

Many seniors declined home medical care for fear of COVID, causing new or worsening conditions

 COVID-19 interrupted or delayed medical treatment for many people who chose to put off elective procedures or couldn't get in to see a specialist. 

 

But new research from the University of Michigan finds another population was affected: Many homebound older adults canceled medically necessary home-based health care services out of fear of getting COVID-19. This caused new or worsening medical conditions for a number of patients, and home-based health care providers reported feeling that they lacked sufficient information and training to advise patients through the process of deciding whether or not to continue care. 

 

"One home health care agency representative said their agency's patient load decreased by 38% as a result of patients canceling services," said study first author Jennifer Inloes, a Doctor of Nursing Practice student at the U-M School of Nursing. "It really highlighted the level of fear among patients receiving home-based health care services at the early part of the pandemic." 

 

Both family members and patients canceled services, and the large number of cancellations surprised Inloes. 

 

"I understood why patients might cancel in-person visits or elective surgeries because there are so many potential points of infection associated with office or hospital-based care," she said. "I wasn't prepared to hear about so many patients declining home-based health care services, since home-based health care is a much more controlled interaction with fewer potential points of infection."

 

Disease management continues to shift toward a home health care model, but there's not much literature on how public health emergencies impact continuity of home health care. To learn more, researchers interviewed 27 Medicare-certified home health providers in eight U.S. counties to better understand older adults' decision making around home-based care service during COVID-19. 

 

The findings emphasize the large role emotion plays in medical decision making, and challenge the assumption that given enough accurate educational information, patients make rational decisions in their best interests. Inloes said her research highlights the importance of carefully weighing the well-known benefits of home-based health care services with the potential negative consequences of canceling services. 

 

"For example, home-based health care providers are trained in infection control precautions, so the risk of becoming infected with COVID-19 from a provider coming into the home is fairly small," she said. "However, a patient experiencing a preventable refusal-related complication that requires emergency department treatment has now inadvertently increased their risk of COVID-19 exposure due to the larger number of providers, patients and family members in the emergency department vs. the home setting."

 

It's unknown if more older adults avoided infection by isolating than were harmed by negative health outcomes of refusing care––and the answer to that question isn't black and white, Inloes said. In addition to new or worsening conditions, previous research has found that pandemic-induced isolation also negatively affected older adults, which is an important consideration.  

 

"For some, but certainly not all patients, a home-based health care provider might be their only regular visitor, so we need to consider that aspect when determining the risks and benefits of an individual's decision to cancel care," she said. 

 

The question is not one of right or wrong. 

 

"Palliative care, which is a specialty that I wish more health care providers received training in, discourages framing patient decisions in terms of right or wrong," she said. "As health care providers, our job is to help our patients live as well as possible in accordance with their individual values, belief systems and goals. I know I've helped an individual come to the 'right' decision if they can clearly articulate how the choice they've made, whether it's to continue or cancel care, aligns with those three things." 

The study was published in the Journal of Gerontological Nursing. Sue Anne Bell, assistant professor at the School of Nursing, is the principal investigator. 

Study: Home-Based Care Provider Perspectives on Care Refusal During the COVID-19 Pandemic 

 

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JOURNAL

Journal of Gerontological Nursing

https://www.eurekalert.org/news-releases/977020

Testing of plane wastewater showed ‘failure’ of COVID-era air travel measures

 Almost all planes arriving at three UK airports during a period of Covid restrictions had the SARS CoV-2 virus in their wastewater, according to newly published research. The virus was also found in wastewater at arrival terminals.

Bangor University scientists, who pioneered the use of wastewater testing to track SARS-CoV2 in the UK, wanted to find out whether wastewater testing could be used as a way of monitoring the general health of passengers on flights coming into the country in future. The study was funded by the UK’s Health Security Agency and is published in PLOS Global Public Health.

The team tested the toilet tank water taken from long haul and short haul flights entering the UK at Heathrow, Edinburgh and Bristol airports over a three-week period between 8-31 March 2022.  Samples were also collected from sewers connected to the arrival halls in the airport terminals and at a wastewater treatment plant in the vicinity of each airport.

The COVID-19 restrictions were lifted in England on the 18th March 2022, removing the requirement for unvaccinated passengers to take a pre-departure test and a day 2 post arrival test to prove their Covid status. But the researchers found little difference in the concentrations of SARS-CoV-2 in wastewater before and after that date.

Professor Davey Jones from Bangor University’s School of Natural Sciences, said,

“Despite all the intervention measures that the UK had in place to try to stop people with the illness getting on flights to the UK, almost every single plane we tested contained the virus, and most of the terminal sewers too. That might have been because people developed symptoms after testing negative; or were evading the system, or for some other reason. But it showed that there was essentially a failure of border control in terms of Covid surveillance.”

Earlier research by the team may explain why. In a poll of 2000 adults, 23% of respondents admitted that they had previously boarded a flight back to the UK while feeling ill. That survey also asked respondents about their toilet habits on flights, and found that 13% of individuals catching a short haul flight would be likely to defecate on the plane; with a higher proportion seen in long haul passengers, at around 36% of the total. Based on this information, together with Covid shedding rates, the team estimated that if wastewater sampling was set up at airports  in future, it could capture 8-14% of SARS-CoV-2 cases entering the UK via air travel.

The researchers believe wastewater sampling could form part of a future infectious disease surveillance system for the UK. Future sampling could also pick up other infections, such as  Norovirus or Enterovirus, potentially giving a clearer picture of what pathogens are entering the country.

Researcher Dr Kata Farkas said: “This is about getting an overall picture to help UK health systems to be prepared, or, if possible, have an advance warning, of emerging diseases. It wouldn’t be feasible to test every flight arriving, but taking wastewater from arrivals at a single airport terminal used for long-haul arrivals may provide an estimate of diseases entering the country.”

She added: “At the moment we have no idea how many people come into the country carrying different diseases, partly because no one wants to be tested on the spot. Wastewater monitoring gives us a snapshot of the infectious diseases passengers may carry upon arrival.”

‘Wastewater-based monitoring of SARS-CoV-2 at UK airports and its potential role in international public health surveillance’ is published today in PLOS Global Public Health.

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JOURNAL

PLOS Global Public Health

DOI

10.1371/journal.pgph.0001346 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Wastewater-based monitoring of SARS-CoV-2 at UK airports and its potential role in international public health surveillance

ARTICLE PUBLICATION DATE

19-Jan-2023

https://www.eurekalert.org/news-releases/976838

Stopping a rare childhood cancer in its tracks

 Scientists at Cold Spring Harbor Laboratory (CSHL) have discovered a new drug target for Ewing sarcoma, a rare kind of cancer usually diagnosed in children and young adults. Their experiments show that the cells causing this cancer can essentially be reprogrammed with the flick of a genetic switch.

Shutting down a single protein forces the cancer cells to take on a new identity and behave like normal connective tissue cells, a dramatic change that reins in their growth. This discovery suggests researchers may be able to stop Ewing sarcoma by developing a drug that blocks the protein known as ETV6.

Ewing sarcoma causes tumors to grow in bones or the soft tissues surrounding them. Once a tumor begins to spread to other parts of the body, it can be very difficult to halt the disease’s progression. Even for patients with positive outcomes, treating Ewing sarcoma often causes toxic side effects. New treatments are badly needed, says CSHL Professor Christopher Vakoc, who led the research on ETV6.

Vakoc and his colleagues became excited about ETV6 when their experiments revealed that Ewing sarcoma cells seem uniquely dependent on this protein. “This protein is present in all cells. But when you perturb the protein, most normal cells don’t care,” he says. “The process by which the sarcoma forms turns this ETV6 molecule—this relatively innocuous, harmless protein that isn’t doing very much—into something that’s now controlling a life-death decision of the tumor cell.”

Postdoctoral researcher Yuan Gao works in Vakoc’s lab. When Gao blocked ETV6 in Ewing sarcoma cells grown in the lab, she witnessed a dramatic transformation. “The sarcoma cell reverts back into being a normal cell again,” she says. “The shape of the cell changes. The behavior of the cells changes. A lot of the cells will arrest their growth. It’s really an explosive effect.”

Vakoc and Gao hope other researchers will use what they’ve learned to begin exploring potential therapies for Ewing sarcoma that work by switching off ETV6. They say their biochemical analyses, which identify specific spots in the ETV6 protein that are key to its function in cancer cells, could help guide drug development. Because their experiments have shown that most cells are unaffected by the loss of ETV6 activity, they are optimistic that such a drug might be able to eliminate cancer cells while causing few, if any, side effects.

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JOURNAL

Nature Cell Biology

DOI

10.1038/s41556-022-01060-1 

ARTICLE TITLE

ETV6 dependency in Ewing sarcoma by antagonism of EWS-FLI1-mediated enhancer activation

ARTICLE PUBLICATION DATE

19-Jan-2023

https://www.eurekalert.org/news-releases/976648

Small molecule can restore visual function after optic nerve injury

 Traumatic injury to the brain, spinal cord and optic nerve in the central nervous system (CNS) are the leading cause of disability and the second leading cause of death worldwide. CNS injuries often result in a catastrophic loss of sensory, motor and visual functions, which is the most challenging problem faced by clinicians and research scientists. Neuroscientists from City University of Hong Kong (CityU) recently identified and demonstrated a small molecule that can effectively stimulate nerve regeneration and restore visual functions after optic nerve injury, offering great hope for patients with optic nerve injury, such as glaucoma-related vision loss.

"There is currently no effective treatment available for traumatic injuries to the CNS, so there is an immediate need for potential drug to promote CNS repair and ultimately achieve full function recovery, such as visual function, in patients," said Dr Eddie Ma Chi-him, Associate Head and Associate Professor in the Department of Neuroscience and Director of the Laboratory Animal Research Unit at CityU, who led the research.

Enhancing mitochondrial dynamics and motility is key for successful axon regeneration

Axons, which are a cable-like structure that extends from neurons (nerve cells), are responsible for transmitting signals between neurons and from the brain to muscles and glands. The first step for successful axon regeneration is to form active growth cones and the activation of a regrowth programme, involving the synthesis and transport of materials to regrow axons. These are all energy-demanding processes, which require the active transport of mitochondria (the powerhouse of the cell) to injured axons at the distal end.

Injured neurons therefore face special challenges that require long-distance transport of mitochondria from the soma (cell body) to distal regenerating axons, where axonal mitochondria in adults are mostly stationary and local energy consumption is critical for axon regeneration.

A research team led by Dr Ma identified a therapeutic small molecule, M1, which can increase the fusion and motility of mitochondria, resulting in sustained, long-distance axon regeneration. Regenerated axons elicited neural activities in target brain regions and restored visual functions within four to six weeks after optic nerve injury in M1-treated mice.

Small molecule M1 promotes mitochondrial dynamics and sustains long-distance axon regeneration

"Photoreceptors in the eyes [retina] forward visual information to neurons in the retina. To facilitate the recovery of visual function after injury, the axons of the neurons must regenerate through the optic nerve and relay nerve impulses to visual targets in the brain via the optic nerve for image processing and formation," explained Dr Ma.

To investigate whether M1 could promote long-distance axon regeneration after CNS injuries, the research team assessed the extent of axon regeneration in M1-treated mice four weeks after injury. Strikingly, most of the regenerating axons of M1-treated mice reached 4mm distal to the crush site (i.e. near optic chiasm), while no regenerating axons were found in vehicle-treated control mice. In M1-treated mice, the survival of retinal ganglion cells (RGCs, neurons that transmit visual stimuli from the eye to the brain) was significantly increased from 19% to 33% four weeks after optic nerve injury.

"This indicates that the M1 treatment sustains long-distance axon regeneration from the optic chiasm, i.e. midway between the eyes and target brain region, to multiple subcortical visual targets in the brain. Regenerated axons elicit neural activities in target brain regions and restore visual functions after M1 treatment," Dr Ma added.

M1 treatment restores visual function

To further explore whether M1 treatment can restore visual function, the research team gave the M1-treated mice a pupillary light reflex test six weeks after the optic nerve injury. They found that the lesioned eyes of M1-treated mice restored the pupil constriction response upon blue light illumination to a level similar to that of non-lesioned eyes, suggesting that M1 treatment can restore the pupil constriction response after optic nerve injuries.

In addition, the research team assessed the response of the mice to a looming stimulus -- a visually induced innate defensive response to avoid predators. The mice were placed into an open chamber with a triangular prism-shaped shelter and a rapidly expanding overhead-black circle as a looming stimulus, and their freeze and escape behaviours were observed. Half of the M1-treated mice responded to the stimulus by hiding in a shelter, showing that M1 induced robust axon regeneration to reinnervate subcortical visual target brain regions for complete recovery of their visual function.

Potential clinical application of M1 for repairing nervous system injury

The seven-year-long study highlights the potential of a readily available, non-viral therapy for CNS repair, which builds on the team's previous research on peripheral nerve regeneration using gene therapy.

"This time we used the small molecule, M1, to repair the CNS simply by intravitreal injection into the eyes, which is an established medical procedure for patients, e.g. for macular degeneration treatment. Successful restoration of visual functions, such as pupillary light reflex and response to looming visual stimuli was observed in M1-treated mice four to six weeks after the optic nerve had been damaged," said Dr Au Ngan-pan, Research Associate in the Department of Neuroscience.

The team is also developing an animal model for treating glaucoma-related vision loss using M1 and possibly other common eye diseases and vision impairments such as diabetes-related retinopathy, macular degeneration and traumatic optic neuropathy. Thus, further investigation is warranted to evaluate the potential clinical application of M1. "This research breakthrough heralds a new approach that could address unmet medical needs in accelerating functional recovery within a limited therapeutic time window after CNS injuries," said Dr Ma.

Journal Reference:

1. Ngan Pan Bennett Au, Raza Chand, Gajendra Kumar, Pallavi Asthana, Wing Yip Tam, Kin Man Tang, Chi-Chiu Ko, Chi Him Eddie Ma. A small molecule M1 promotes optic nerve regeneration to restore target-specific neural activity and visual function. Proceedings of the National Academy of Sciences, 2022; 119 (44) DOI: 10.1073/pnas.2121273119

https://www.sciencedaily.com/releases/2023/01/230120093105.htm

Klain White House Departure Reported 1 Day After Scapegoat Found For Slow-Walking Classified Docs

 After working for Joe Biden on and off for more than three decades, White House Chief of Staff Ron Klain is expected to step down in coming weeks because he's 'ready to move on,' the NY Times reports.

The news of Klain's departure comes one day after the White House threw senior adviser Anita Dunn under the bus for the decision to 'keep the public information flow to a trickle' regarding President Biden's classified document scandal.

Is Klain's departure related to the decision to slow-walk news that classified documents from Biden's VP days were found in unauthorized locations? We don't know at this stage, but we assume Klain was apprised of Dunn's strategy, and perhaps even signed off on it. Now that we're in the 'who said what, and when' phase of a Special Counsel investigation into the matter, nothing is off the table. Maybe he was just tired of performing elder care?

The departure would also come at a time when the White House faces a widening array of political and legal threats from a newly appointed special counsel investigating the improper handling of classified documents and a flurry of other inquiries by the newly installed Republican majority in the House. The next chief of staff will be charged with managing the defense of Mr. Biden’s White House and any counterattack as the 2024 election approaches. -NY Times

The Times suggests Klain's departure could be related to Biden's anticipated 2024 reelection campaign, and says "advisers predict more moves as some aides shift from the White House to the campaign."

So - not rats bailing from a sinking ship.

The Times notes that Klain has been so influential that Republicans 'derisively call him a virtual prime minister,' and Democrats 'blame him when they are disappointed in a decision.'

Klain has also presided over 'a rash of troubles' that have tanked public support for Biden - including the highest inflation in 40 years, and the creation of a border crisis after shredding much of former President Trump's border policy.

On that note, the Times also reports that Biden's national economic adviser, Brian Dees, is expected to leave later this year.

As for those classified documents

The Times reported on Friday that White House senior adviser, Anita Dunn - along with her husband, Biden's personal lawyer Bob Bauer, and White House counsel Stuart F. Delery and Richard Sauber, were part of at "tight circle" involved in discussions on how to deal with the matter.

More via The Times,

Details about the documents — where they were found, what they are about, where they came from — remain elusive more than 10 days after their existence was first made public by CBS News.

The White House has refused to explain why it took nearly six weeks after the initial discovery of documents to search the president’s home in Wilmington, Del., where a second batch was found on Dec. 20. And it has not said why personal lawyers for the president who do not have security clearances were the ones conducting the searches, but people close to the case said that was done with the approval of the Justice Department.

...

Once the discovery of the original batch of documents was revealed, Ms. Dunn was adamant that the White House should keep the public information flow to a trickle and focus instead on how different Mr. Biden’s case was from the broader investigation into his predecessor, according to people familiar with the discussions.

Ms. Dunn also stressed the need to underscore the differences between Mr. Biden’s cooperation with the archives and Justice Department and Mr. Trump’s defiance.

Impeachment when?

https://www.zerohedge.com/markets/ron-klain-white-house-departure-reported-one-day-after-scapegoat-found-classified-document