US urges 'transparent' WHO inquiry into Covid origins

SharecloseShare pageCopy linkAbout sharingimage copyrightReutersThe US health secretary has urged the World Health Organization to ensure the next phase of investigation into Covid-19’s origins is “transparent”. Speaking to a ministerial-level WHO meeting, Xavier Becerra said international experts should be allowed to evaluate the source of coronavirus. US media reports suggest growing evidence the virus could have emerged from a laboratory in China. Covid-19 was first detected in 2019 in Wuhan, in central Hubei province.Since then, more than 167 million cases and 3.4 million deaths have been reported worldwide.In March this year, the WHO issued a report written jointly with Chinese scientists on the origins of Covid-19, saying the chances of it having started in a lab were “extremely unlikely”. The WHO acknowledged further study was needed. But questions have persisted and reports attributed to US intelligence sources say three members of the Wuhan Institute of Virology were admitted to hospital in November 2019, several weeks before China acknowledged the first case of the new disease in the community. image copyrightGetty ImagesBeijing has angrily rejected the reports, repeatedly suggesting the virus may have come from a US laboratory instead. Speaking to the WHO on Tuesday, US Secretary for Health and Human Services Xavier Becerra did not mention China by name. But he made it clear the US expected more rigour from the next stage of any investigation.”The Covid-19 pandemic not only stole a year from our lives, it stole millions of lives,” Mr Becerra said in an address to the World Health Assembly, a conference organised by the WHO. He added: “Phase 2 of the Covid origins study must be launched with terms of reference that are transparent, science-based and give international experts the independence to fully assess the source of the virus and the early days of the outbreak.”The White House said on Tuesday that it expected from the WHO an “expert-driven evaluation of the pandemic’s origins that is free from interference or politicisation”. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases and US President Joe Biden’s chief medical adviser, has maintained he believes the virus was passed from animals to humans, though he conceded this month he was no longer confident Covid-19 had developed naturally.The lab leak claims were widely dismissed last year as a fringe conspiracy theory, after then-President Donald Trump said Covid-19 had originated from the Wuhan Institute of Virology. Many US media outlets described such claims as debunked or false.On Tuesday, Mr Trump sought to take credit in an emailed statement to the New York Post. “To me it was obvious from the beginning but I was badly criticised, as usual,” he said. “Now they are all saying: ‘He was right.'”

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Mount Sinai Seeks to Expand School Virus Testing Program

The health system, which is preparing to open a new laboratory that could process 100,000 tests a day, wants to take its program to public schools this fall.Every week, students at KIPP Infinity Middle School, in West Harlem, file into a large auditorium and take their places on the designated floor markings, making sure to stand six feet apart. Then they pull down their masks and fill sterile tubes with their spit.The school’s teachers try to make the experience fun, running competitions to see who can fill their tube fastest and holding dance contests while students wait for their classmates to finish.“It’s kind of enjoyable,” said Bradley Ramirez, a seventh grader at the school who likes math and Minecraft. “It’s way better than just sticking a stick up your nose.”Bradley and his classmates are participants in a coronavirus testing pilot program created by the Mount Sinai Health System, the nonprofit Pershing Square Foundation and KIPP NYC, a network of 15 local charter schools. Since early March, the program has conducted more than 13,000 saliva-based tests of KIPP students, teachers and staff members, identifying several dozen cases of the virus.Now Mount Sinai and Pershing Square are hoping to expand. On Tuesday they announced the Mount Sinai Covid Lab initiative, inviting additional charter schools, as well as local businesses and organizations, to sign up for the saliva-based testing program. They are putting the finishing touches on a new laboratory that they say will be capable of processing as many as 100,000 coronavirus tests a day and are preparing a formal proposal to take the program to New York City’s public schools this fall.The announcement comes the day after Mayor Bill de Blasio said that the city planned to fully reopen schools, eliminating remote learning, in the fall.“The way you keep a school safe, the way you make teachers feel comfortable with the reopening of schools, the way you make parents feel comfortable sending their kid, is you have a testing program,” said William A. Ackman, a hedge fund manager who founded the Pershing Square Foundation.The testing program originated in December, when Mr. Ackman decided that he wanted to find a way to get New York City children back to school and approached Mount Sinai with a proposal: What if he provided funding for the hospital to build a laboratory that could process 100,000 coronavirus tests a day? The hope was that the lab could devote some of that capacity to corporate clients, such as businesses that wanted to test their employees, and use the revenue to fund wide-scale testing for New York City schoolchildren.Mount Sinai quickly agreed. “We began on a concerted effort that people at Mount Sinai have really rallied around,” said Dr. David Reich, president and chief operating officer of Mount Sinai Hospital. “It’s just one of those projects where you never have to worry about people wanting to show up for your Zoom meeting — they’re all there, and they’re all smiling.”The Pershing Square Foundation, whose trustees are Mr. Ackman and his wife, Neri Oxman, agreed to provide $20 million, and Mount Sinai began to convert an old laboratory space at its downtown campus into a high-volume coronavirus test processing center.Dr. Alberto Paniz-Mondolfi, a pathologist with the Mount Sinai Health System who led development of the new saliva test: “This was practical science, designed by parents to get their kids back to school.”Chang W. Lee/The New York TimesAt the time, scientists at Mount Sinai’s Icahn School of Medicine were among a number of groups across the country that were working to develop saliva-based coronavirus tests. The gold standard diagnostic tests are known as P.C.R. tests, which can detect even minute amounts of the virus in biological specimens. During the early months of the pandemic, these tests generally required medical professionals to stick a swab deep into a patient’s nasopharynx, a procedure that can be deeply uncomfortable and put clinicians at risk.Saliva-based P.C.R. tests, many scientists came to believe, would be safer and less invasive. They would also be much more suitable for young children than the deep, nasopharyngeal swabs. “A brain scoop, for a kid? Really? That’s a no-no,” said Dr. Alberto Paniz-Mondolfi, a pathologist at Mount Sinai who led development of the new saliva test.As the partnership between Mount Sinai and Pershing Square began to take shape, Dr. Paniz-Mondolfi and his colleagues accelerated their work, validating their saliva test in 60 adult patients. But they knew that in the real world, children could not always be relied upon to follow clinical procedures to the letter.“When we start getting this from the schools, we’re going to have pieces of pretzels, old gum floating in the saliva,” Dr. Paniz-Mondolfi said.So Dr. Paniz-Mondolfi and his colleagues asked their own children to make a sacrifice for science: to snack on an array of junk food, including pizza and Oreos, and then spit into some testing tubes. Using these samples, the researchers confirmed that even if a student’s sample was contaminated with one of these foods, the tests should still work properly.“This was practical science, designed by parents to get their kids back to school,” Dr. Paniz-Mondolfi said.Then it was time to pilot the tests in a real school environment. In January, Mount Sinai connected with KIPP NYC, which had been offering remote instruction since last spring. But it was hoping to reopen its schools in March, and administrators knew they would need to do some kind of in-school virus testing.“One of the biggest fears that we had was around what it would mean to keep students safe,” said Glenn Davis, the principal of KIPP Infinity Middle School.Mount Sinai and KIPP NYC agreed to begin a pilot saliva-testing project at five schools. The testing program, which eventually grew to include nine KIPP schools, was free for the schools and mandatory for all students who opted to return to in-person learning. (Some families chose to continue with remote education.)Students, teachers and staff members are tested once a week. Medical assistants from Mount Sinai supervise the saliva collection and pack the bar-coded tubes into coolers for transportation back to the laboratory. (The samples are currently being processed at an existing Mount Sinai lab, but will be sent to the new lab when it opens next month.)During the pilot project, 99.2 percent test results were returned within 24 hours, Mount Sinai says. Students or staff members who test positive typically have to quarantine for 10 days.If a student tests positive, Mount Sinai also offers to send a team of “swabbers” to his or her home to administer free coronavirus tests to their family members and close contacts.“We’ve detected a few mini outbreaks in that fashion, and hopefully prevented them from spreading by virtue of this screening program in the schoolkids,” Dr. Reich said.Bradley Ramirez, right, desperately wanted to return to school and was able to overcome his mother’s Covid concerns with the help of an informational video about the Mount Sinai testing program.Mount Sinai Health SystemBetween March 10, when the pilot project began, and May 9, Mount Sinai conducted 13,067 tests and identified 46 coronavirus cases, a positivity rate of 0.4 percent. There have been no false positives and no known false negatives, Mount Sinai says.The Mount Sinai team has submitted the data to the Food and Drug Administration, hoping to receive an emergency use authorization for the test.Later this week, Mount Sinai will submit a formal proposal to New York City to take its testing program to the city’s public schools when they reopen in the fall. Mount Sinai declined to disclose the terms of the proposal, including what it plans to charge schools for the tests, but says it hopes to attract commercial clients to help defray, or possibly even eliminate, costs for schools.In the meantime, it is approaching other charter school organizations in the city about using its tests during their summer sessions and programs.“We can’t just sit there when this lab goes live in June and say, ‘OK, we’re waiting for September,’” Dr. Reich said. “Before the fall, we need to be doing a lot of tests.” The lab will initially have the capacity to run 25,000 tests a day, with the ability to scale up to 100,000 if there is sufficient interest.For its part, KIPP NYC plans to expand the program to all of its schools in the fall, although the testing frequency may change, said Efrain Guerrero, managing director of operations for KIPP NYC. “I think parents see it and staff see it as just an additional safety measure that they appreciate,” he said. “For us it’s a no-brainer to continue to test at some frequency.”Olga Ramirez, Bradley’s mother, had not initially wanted him to return to in-person learning. “I was very afraid at first,” she said. But Bradley, who desperately wanted to go back to school, managed to convince her, with the help of an informational video about the Mount Sinai testing program.Ms. Ramirez now thinks that returning to school was the right decision. Bradley’s virus tests have all come back negative, and his grades are up since returning to in-person learning.“I’ve seen his grades improve quite a lot, and I feel that my son is in good hands,” she said. She’s not alone, she added. “There’s so many mothers who are feeling the way I do.”Elda Cantú

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Asthma medication use and exacerbations

How does the switch to a high-deductible health plan affect children with asthma? A new study led by researchers at the Harvard Pilgrim Health Care Institute suggests that enrollment in a high-deductible health plan (HDHP) may not be associated with changes in asthma medication use or asthma exacerbations when medications are exempt from the deductible. The findings were published in JAMA Pediatrics on May 10.
To treat asthma, clinical guidelines recommend the use of controller medications, but adherence to these medications is generally suboptimal, putting those affected at risk for asthma exacerbations. High out-of-pocket costs have been associated with decreased controller medication use and adverse asthma outcomes for children and adults. While most evidence about HDHPs has come from studies focused on adult populations, the study team, led by Alison Galbraith, MD, MPH, lead author and Associate Professor in the Department of Population Medicine at Harvard Medical School, examined how enrollment in HDHPs may affect asthma controller medication use and exacerbation in children.
“One challenge of insurance design is balancing affordable coverage with access to necessary care for chronic conditions for both children and adults,” said Dr. Galbraith. “Our findings highlight the potential protective effect of exempting asthma medications from the deductible in high-deductible health plans.”
The study population, drawn from a large, national, commercial database, included children (ages 4 to 17) and adults (ages 18-64) years with persistent asthma who switched from traditional plans to HDHPs during a 24-month period. Compared to those who remained in traditional plans, children switching to HDHPs experienced small decreases in annual 30-day fills for inhaled corticosteroid-long-acting beta agonist medications but not for other controller medications. Adults switching to HDHPs did not have significant reductions in 30-day fills for any controller medications. There were no statistically significant differences in medication adherence, oral steroid bursts, or asthma-related ED visits for children or adults.
Regarding possible next steps, Dr. Galbraith adds, “Asthma is a major cause of preventable disease burden for both children and adults. Policy makers should consider adopting value-based designs and other policies exempting important medications for asthma and other chronic conditions — which might prevent adverse clinical outcomes — from the deductible.”
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Materials provided by Harvard Pilgrim Health Care Institute. Note: Content may be edited for style and length.

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SARS-CoV-2: Estimating infectiousness

What started as the preliminary analysis of routine laboratory data has since evolved into the largest-ever study of viral load levels in patients with SARS-CoV-2. A team of researchers from Charité — Universitätsmedizin Berlin have now analyzed the PCR samples of more than 25,000 persons with COVID-19. Working under the leadership of Prof. Dr. Christian Drosten, the team determined the viral loads of each individual sample and used their results to estimate levels of infectiousness. The research, which has been published in Science, provides a clear idea of the infectiousness of the disease in different age groups and at different levels of disease severity. It also provides new insights into the B.1.1.7 variant.
According to the reproductive number (R 0), a person infected with SARS-CoV-2 will, on average, transmit their infection to three to five other people. While it is a useful metric in an epidemiological setting, ‘R 0’ does not lend itself to estimating the risk of transmission at the individual or group level. Once normal social and environmental factors are removed from the equation, individuals can differ markedly in terms of their infectiousness and the length of time during which they actively shed the virus.
To better understand and estimate infectiousness in specific groups of individuals, a team led by Prof. Dr. Christian Drosten, Director of Charité’s Institute of Virology and a researcher at the German Center for Infection Research (DZIF), analyzed the PCR samples of more than 25,000 COVID-19 cases in order to determine their ‘viral loads’. A sample’s viral load — the total number of copies of the SARS-CoV-2 genome contained in the sample — provides a rough estimate of the quantity of virus present in a patient’s throat and, as such, is a useful metric for estimating an individual’s infectiousness. To further improve their estimates, the researchers also applied findings regarding the minimum viral load threshold typically required for the successful isolation of SARS-CoV-2 in cell culture (where isolation indicates the presence of infectious virus). Sequential samples were available for more than 4,300 of the cases studied. Using these to track throat viral load data over time, the researchers were able to model the typical development of viral loads over the course of the infection. The researchers then looked for significant differences in their data, specifically in relation to different age groups, disease severity and virus variants.
No notable differences in viral load levels were recorded among SARS-CoV-2-positive individuals aged between 20 and 65 years, the average throat swab sample containing approximately 2.5 million copies of the SARS-CoV-2 genome. Viral loads were found to be lowest in very young children (0 to 5 years). Levels started at approximately 800,000 copies of the viral genome, increased with age, and approached adult levels in older children and adolescents.
“While these numbers look very different at first glance, it is crucial to remember that viral load results are shown on a logarithmic scale,” says Prof. Drosten. “The differences in viral loads found in the youngest children are, in fact, barely below the threshold at which we would normally consider them clinically relevant. Crucially, one also has to understand how we arrive at these values and take this into account when interpreting them.” Highlighting the differences in the methodology of sample collection between children and adults, the virologist adds: “Children’s swabs are significantly smaller in size and collect less than half the sample quantity normally available for PCR testing. Moreover, the level of discomfort involved with the procedure means that deep nasopharyngeal swabs are often replaced with simple throat swabs. This of course further reduces the amount of viral material collected. For this reason, we fully expect that, in children, the same level of viral replication will produce lower viral load results during PCR testing.”
When comparing peak viral loads in laboratory samples, the researchers estimated levels of infectivity in the youngest children (0 to 5 years) to be at approximately 80 percent of that found in adults. As previously, values for school-aged children and adolescents were found to be approaching adult values. “This shows that viral loads are not directly proportional to infectivity and cannot be converted directly,” explains Prof. Drosten. He adds: “Even these data-based estimates of infectivity have to be corrected upwards because of the different methods of sample collection used in children. All of this forms part of a clinical virologist’s overall assessment. My initial assumption, that all age groups have roughly the same level of infectivity, has been confirmed, both by this and by other studies.”
A symptom-based comparison confirmed observations previously made in COVID-19 cases, namely that even asymptomatic individuals can have very high viral loads. Individuals who required hospitalization were found to have higher viral loads than others over the entire course of the disease. Based on their new models of viral load courses over time, the researchers estimate that individuals infected with SARS-CoV-2 reach peak viral load levels in their throats as early as 1 to 3 days before the onset of symptoms.
Approximately 9 percent of the COVID-19 cases tested showed extremely high viral loads of one billion copies per sample or higher. More than a third of these potentially highly infectious individuals had either no symptoms or only mild symptoms. “These data provide a virological foundation for the notion that a minority of infected individuals cause the majority of all transmissions,” explains Prof. Drosten. He adds: “The fact that this includes so many people without any relevant symptoms underlines the importance of pandemic control measures such as social distancing and mandatory mask-wearing.”
In samples collected from individuals infected with the B.1.1.7 (‘UK’ or ‘British’) variant, average viral loads were found to be increased by a factor of ten, while laboratory-based estimates of infectivity were increased by a factor of 2.6. To arrive at these data, the researchers took viral load data from approximately 1,500 cases infected with B.1.1.7 and compared them with data from approximately 1,000 people infected with other variants who had been tested at the same testing centers, outpatient departments and clinical wards around the same time. Prof. Drosten adds: “Laboratory studies may not as yet be in a position to provide a definitive explanation, but one thing is clear: B.1.1.7 is more infectious than other variants.”
The researchers plan to continue their work on viral loads throughout the course of the pandemic. They hope to gain insights into the changes which occur as new variants arise as the virus adapts to increasing levels of population immunity.
About the study
The study was authored by scientists from Charité — Universitätsmedizin Berlin, the German Center for Infection Research, the University of Cambridge, the Norwegian Institute of Public Health, the University of Oslo, Labor Berlin — Charité Vivantes GmbH, the Christian-Albrechts-Universität zu Kiel, and Labor Dr. Krause und Kollegen MVZ GmbH.

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A COVID-fighter's guide to T cells

In a new paper, scientists from La Jolla Institute for Immunology (LJI) bring together research findings from COVID-19 researchers around the world. The results are striking: human T cells can target more than 1,400 sites on the SARS-CoV-2 virus.
“Our lab and many others have shown this very broad and diverse T cell response,” says LJI Research Assistant Professor Daniela Weiskopf, Ph.D., co-author of the Cell Host & Microbe review.
This kind of research review, called a “meta-analysis,” pools the results of multiple studies, and the researchers give close consideration to how the studies were conducted.
In the case of COVID-19, a global meta-analysis of T cell response studies is especially helpful because different patient populations can have vastly different immune responses, based on their genetic differences and past disease history.
“This really highlights how the study of SARS-CoV-2 has been a global undertaking,” says LJI Professor Alessandro Sette, Dr.Biol.Sci, senior author of the review and member of the LJI Center for Infectious Disease and Vaccine Research. “To combine information from all the different labs is a powerful thing.”
Key points: The researchers evaluated all 25 known human T cell response studies conducted between the beginning of the COVID-19 pandemic and March 15, 2021. The studies show human T cell responses against 1,434 CD4 and CD8 epitopes. Epitopes are sites on SARS-CoV-2 that T cells can recognize. Grouping these studies together for this larger analysis has revealed several “immunodominant” sites on the virus. These sites are where T cells are most prone to homing in on. This broad T cell response makes it difficult for SARS-CoV-2 variants to acquire enough mutations to “escape” the body’s response against the virus.Sette adds that this analysis can help researchers monitor whether T cells are mounting effective responses as they encounter viral variants — and vaccines. “Knowing what the key sites on the SARS-CoV-2 spike protein are especially important for monitoring immune responses to COVID-19 vaccines,” he says.

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Researchers uncover mechanism related to severe post-COVID-19 disease in children

A multidisciplinary team from MassGeneral Hospital for Children (MGHfC), Brigham and Women’s Hospital and other institutions have identified the mechanism of how an extremely rare but serious post-COVID-19 complication develops in children and adolescents. Led by MGHfC pediatric pulmonologist Lael Yonker, MD, researchers determined that viral particles remaining in the gut long after an initial COVID-19 infection can travel into the bloodstream, instigating the condition called Multisystem Inflammatory Syndrome in Children (MIS-C).
The syndrome can occur several weeks after an initial infection; symptoms include high fever, abdominal pain, vomiting, diarrhea, rash and extreme fatigue. The hyperinflammatory response and “cytokine storm” seen in MIS-C can lead to extensive damage in the heart, liver and other organs.
Eighty percent of children hospitalized with MIS-C develop severe cardiac pathology and face a prolonged hospital stay and extensive recovery period. Current treatment strategies include an aggressive, long-term course of steroids and intravenous immunoglobulin.
MIS-C occurs in less than 1 percent of children with confirmed SARS-CoV-2 infection. As of May 3, 2021, the U.S. Centers for Disease Control and Prevention reported 3,742 children diagnosed with MIS-C and 35 deaths. U.S. statistics are skewed heavily toward Latino and Black children, with a total of 63 percent in cases with race or ethnicity listed.
In their recent study published in the Journal of Clinical Investigation, which included 100 children (19 with MIS-C, 26 with COVID-19 and 55 healthy controls), the researchers provide insight into the mechanics of MIS-C and identify potential biomarkers for early disease detection, treatment and prevention. They also describe the successful treatment of a 17-month-old infant with MIS-C.
“When we realized that 95 percent of the children with MIS-C had SARS-CoV-2 viral particles in their stool but no or low levels of particles in their noses or throats, we investigated further and found that viral material lingering in the gut long after the first COVID-19 infection could lead to MIS-C,” says Yonker, lead author of the paper. The team hypothesized that SARS-CoV-2 viral particles found in the gastrointestinal tract of children move into the bloodstream, leading to the hyperinflammatory immune response characteristic of MIS-C. “This is the first study showing viral particles in the blood of MIS-C coinciding with the hyperinflammatory response,” says Yonker.

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Impact of coal burning on Yangtze River is comparable to natural processes

A new study finds that fly ash — particles left over from burning coal — make up between 37 and 72 percent of all particulate organic carbon carried by the Yangtze River in China, or around 200,000 to 400,000 tons of carbon per year.
The study, which is the first of its kind, shows just how big an impact fossil fuel consumption has on Earth. Beyond pumping carbon dioxide into the atmosphere, coal burning dumps about as much particulate carbon into the Yangtze River as natural processes do.
The findings were published in the Proceedings of the National Academy of Sciences (PNAS) on May 17.
“About one-fifth of the world’s coal consumption occurs along this river,” says Gen Li, postdoctoral scholar research associate at Caltech and lead author of the PNAS paper. “We knew that would have an impact on the river; we just had no idea how big an impact it would be.”
The Yangtze River is the third largest river in the world, cutting east across central China from the Tibetan plateau to the sea at Shanghai. China is the world’s largest consumer of coal today, burning 2,500 megatons of coal in 2008, when the samples for this study were collected, and over 4,000 megatons of coal in 2020. (Although the total amount of coal burned in China increased from 2008 to 2020, the country also improved its regulation, recollection, and storage of fly ash over that period; now, approximately 80 percent is immediately retrieved.)
Coal fly ash is the unreactive particulate byproduct of burning coal — the fine grains that do not burn but rather become sooty smoke. Those particles, composed of minerals and fossilized particulate organic carbon on the same scale as silt or clay particles, are dangerous when inhaled but are also heavy and settle out of the air.
Most of it is captured for use in industry as an additive to cements and concretes, in which it improves workability as well as overall strength. It is also used in agriculture as a fertilizer. However, a portion of it escapes capture, ultimately collecting in rivers and washing downstream with the normal sediment that erodes out of riverbeds.
“This is a new angle for carbon emissions that we haven’t tracked before,” says Woodward Fischer, professor of geobiology and co-author of the PNAS paper. “The fact that human processes are producing about as much as natural processes in this region shows just how much of a problem this is.”
Next, the team plans to continue to examine the role of coal fly ash in other large river basins near dense populations — for example, the Mississippi River. Meanwhile, the researchers will study sediment cores taken offshore from the Yangtze River outflow to see if they can identify coal fly ash there.
“We’re just beginning to appreciate how rivers are massive conduits for carbon at the earth surface,” Fischer says. “By studying them further, we can quantify, evaluate, and, with future planning, potentially mitigate inimical human impacts on the carbon cycle.”
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Materials provided by California Institute of Technology. Original written by Robert Perkins. Note: Content may be edited for style and length.

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On A Late Show With Stephen Colbert

It was fun appearing virtually on A Late Show with Stephen Colbert on May 24. In this clip taken from our longer conversation, Stephen asked for my thoughts on the nation emerging carefully back to public life and the future challenges of attaining herd immunity in the U.S. to SARS-CoV-2, the coronavirus that causes COVID-19. Stephen also mentioned my Christian faith. That gave me a chance to talk about my ongoing conversations with others of faith to encourage them to accept the gift of a COVID-19 vaccine.

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On A Late Show With Stephen Colbert

NIH Blog Post Date

Tuesday, May 25, 2021

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Silver attacks bacteria, gets 'consumed'

For millennia, silver has been utilized for its antimicrobial and antibacterial properties. Although its use as a disinfectant is widely known, the effects of silver’s interaction with bacteria on the silver itself are not well understood.
As antibiotic-resistant bacteria become more and more prevalent, silver has seen steep growth in its use in things like antibacterial coatings. Still, the complex chain of events that lead to the eradication of bacteria is largely taken for granted, and a better understanding of this process can provide clues on how to best apply it.
In Chemical Physics Reviews, by AIP Publishing, researchers from Italy, the United States, and Singapore studied the impacts an interaction with bacteria has on silver’s structure.
When monitoring the interaction of silver nanoparticles with a nearby E. coli culture, the researchers found the silver undergoes several dramatic changes. Most notably, the E. coli cells caused substantial transformations in the size and shape of the silver particles.
It is often assumed the silver stays unmodified in this process, but the work done by the team shows this not to be true.
The electrostatic interaction between the silver and the bacteria causes some of the silver particles to dissolve as it releases ions to penetrate the bacterial cells. This dissolution modifies the shape of the silver particles, shrinking and rounding them out from triangular shapes into circles.
These effects are even more pronounced if the E. coli cells are pretreated with a molecule to increase the permeability of their membranes before they meet the silver.
“It seems from this study that silver is ‘consumed’ from the interaction,” said Guglielmo Lanzani, one of the authors on the paper and director of the Center for Nano Science and Technology of IIT-Instituto di Tecnologia.
Fortunately, this “consumption” likely does not impact silver’s antimicrobial properties, because the effect is so small.
“We think this does not affect the efficiency of the biocidal process and, due to the tiny exchange of mass, the lifetime is essentially unlimited,” said Giuseppe Paternò, a researcher at IIT and co-author of the study. “The structural modifications, however, affect the optical properties of the metal nanostructures.”
Direct investigations of processes like these are difficult, because laboratories are controlled environments that cannot fully capture the complexities of a biological setting of bacterial cells.
Nevertheless, the group is planning further experiments to explore the chemical pathways that lead to the structural changes in silver. They hope to uncover why silver works better than other materials as an antibacterial surface, and why bacterial membranes are particularly vulnerable to silver, while other cells remain less affected.
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

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For men, low testosterone means high risk of severe COVID-19, study suggests

Throughout the pandemic, doctors have seen evidence that men with COVID-19 fare worse, on average, than women with the infection. One theory is that hormonal differences between men and women may make men more susceptible to severe disease. And since men have much more testosterone than women, some scientists have speculated that high levels of testosterone may be to blame.
But a new study from Washington University School of Medicine in St. Louis suggests that, among men, the opposite may be true: that low testosterone levels in the blood are linked to more severe disease. The study could not prove that low testosterone is a cause of severe COVID-19; low levels could simply serve as a marker of some other causal factors. Still, the researchers urge caution with ongoing clinical trials investigating hormonal therapies that block or lower testosterone or increase estrogen as a treatment for men with COVID-19.
The study appears online May 25 in JAMA Network Open.
“During the pandemic, there has been a prevailing notion that testosterone is bad,” said senior author Abhinav Diwan, MD, a professor of medicine. “But we found the opposite in men. If a man had low testosterone when he first came to the hospital, his risk of having severe COVID-19 — meaning his risk of requiring intensive care or dying — was much higher compared with men who had more circulating testosterone. And if testosterone levels dropped further during hospitalization, the risk increased.”
The researchers measured several hormones in blood samples from 90 men and 62 women who came to Barnes-Jewish Hospital with symptoms of COVID-19 and who had confirmed cases of the illness. For the 143 patients who were admitted to the hospital, the researchers measured hormone levels again at days 3, 7, 14 and 28, as long as the patients remained hospitalized over these time frames. In addition to testosterone, the investigators measured levels of estradiol, a form of estrogen produced by the body, and IGF-1, an important growth hormone that is similar to insulin and plays a role in maintaining muscle mass.
Among women, the researchers found no correlation between levels of any hormone and disease severity. Among men, only testosterone levels were linked to COVID-19 severity. A blood testosterone level of 250 nanograms per deciliter or less is considered low testosterone in adult men. At hospital admission, men with severe COVID-19 had average testosterone levels of 53 nanograms per deciliter; men with less severe disease had average levels of 151 nanograms per deciliter. By day three, the average testosterone level of the most severely ill men was only 19 nanograms per deciliter.
The lower the levels of testosterone, the more severe the disease. For example, those with the lowest levels of testosterone in the blood were at highest risk of going on a ventilator, needing intensive care or dying. Thirty-seven patients — 25 of whom were men — died over the course of the study.
The researchers noted that other factors known to increase the risk of severe COVID-19, including advanced age, obesity and diabetes, also are associated with lower testosterone. “The groups of men who were getting sicker were known to have lower testosterone across the board,” said first author Sandeep Dhindsa, MD, an endocrinologist at Saint Louis University. “We also found that those men with COVID-19 who were not severely ill initially, but had low testosterone levels, were likely to need intensive care or intubation over the next two or three days. Lower testosterone levels seemed to predict which patients were likely to become very ill over the next few days.”
In addition, the researchers found that lower testosterone levels in men also correlated with higher levels of inflammation and an increase in the activation of genes that allow the body to carry out the functions of circulating sex hormones inside the cells. In other words, the body may be adapting to less testosterone circulating in the bloodstream by dialing up its ability to detect and use the hormone. The researchers don’t yet know the implications of this adaptation and are calling for more research.
“We are now investigating whether there is an association between sex hormones and cardiovascular outcomes in long COVID-19, when the symptoms linger over many months,” said Diwan, who is a cardiologist. “We also are interested in whether men recovering from COVID-19, including those with long COVID-19, may benefit from testosterone therapy. This therapy has been used in men with low levels of sex hormones, so it may be worth investigating whether a similar approach can help male COVID-19 survivors with their rehabilitation.”
This study used Washington University’s COVID-19 biorepository and was conducted as a collaboration of the university’s Institute of Clinical and Translational Sciences (ICTS), which includes Saint Louis University School of Medicine.
This work was supported by the National Institutes of Health (NIH), grant numbers R37 AI049653, P30 DK020579, HL107594 and HL143431; and a grant from The Foundation for Barnes-Jewish Hospital to facilitate data collection from the WU350 cohort, which supported these studies. These studies also were supported by the Washington University Institute of Clinical and Translational Sciences, grant number UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the NIH.

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