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Genetic Linkage

How COVID-19 Arose and Amplified Along the Meat Supply Chain

Early in this unforgettable year, a wet market in Wuhan, China, emerged as a possible step along the way, if not the place of origin, of the outbreak that would seed the pandemic of COVID-19. Prescient researchers have reached back to meat samples collected in 2013 and 2014 and used genetic testing to trace what might have happened again more recently: the magnification of viral infection from wild or farmed meat to large markets to restaurants. The report appears in PLoS ONE.

 

"This study shows the wildlife supply chain generates a one-two punch when it comes to spillover risk. It is known to increase contact rates between wildlife and people and here we show how it greatly amplifies the number of infected animals along the way," write Amanda E. Fine from the Wildlife Conservation Society, Viet Nam Country Program in Ha Noi and the Wildlife Conservation Society, Health Program, Bronx, New York, and colleagues.

 

COVID-19 was not a surprise to anyone familiar with the ways of viruses. A lot of folks weren't paying attention, even when repeatedly warned.

Collecting Rats

 

To continue reading, go to DNA Science, where this post first appeared. 

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Mesoblast MSCs Quell Peds GvHD; On Road to FDA Approval?

Graft-versus-host disease (GVHD) is counterintuitive

 

In the weeks and months following a transplant, a major concern is the recipient's immune system rejecting the "foreign" biological material. But in GVHD, the opposite happens: transplanted tissue unleashes a horde of T cells that spark a cascade of inflammation, within 100 days. Typically, GVHD follows a bone marrow transplant (BMT).

 

Eighty Percent Mortality
BMT has been used for more than half a century to treat and possibly cure certain cancers and single-gene conditions like sickle cell disease, immune deficiencies, and lysosomal storage diseases. BMT and hematopoietic stem cell (HSC) transplantation also enable a cancer patient to withstand higher doses of chemotherapy or radiation.

 

Acute GVHD develops in about half of the 30,000 or so patients who receive a BMT from a donor worldwide each year.  In children the complication can be particularly fierce. A blistery rash can become so extreme that the skin peels away, as can the intestinal lining, causing abdominal pain, diarrhea, and nausea and vomiting. Hepatitis may develop.

 

Only 20% of children who have steroid-resistant acute GVHD survive. But a treatment of mesenchymal stromal/stem cells (MSCs), called remestemcel-L (RYONCIL™), from Mesoblast Limited, is boosting survival to the 65-75% range among severely affected children, according to recent clinical trial findings.

 

On August 13, FDA's Oncologic Drugs Advisory Committee, an independent panel of experts who take a first peek at phase III clinical trial results, voted overwhelmingly to advise the agency to continue along the path to approval for RYONCIL. FDA's final meeting is slated for September 30.

 

To continue reading, please go to The Niche, where this post first appeared.  (Photo credit: Rose Spear on Flickr.)

 

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Sniffing Out Stem Cells Behind COVID-Skewed Olfaction

In COVID-19, the sense of smell can diminish, vanish, or oddly skew, for weeks or months. The loss usually starts suddenly and is more than the temporarily dulled chemical senses of a stuffy nose from the common cold. As researchers followed up mounting reports of loss of olfaction, a surprising source of perhaps the longest-lasting cases emerged: stem cells in the olfactory epithelium.

 

A Common Symptom

 

Facebook groups may be ahead of the medical literature in providing vivid descriptions of the loss of olfaction as people swap advice and compare how long they've been unable to smell. The experiences can be bizarre, but at the same time, shared.

 

A favorite robust wine suddenly has no taste.

 

A parent must peek into or feel a child's diaper to see if action is needed.

 

Shower gel reeks, while clean dryer sheets, vinegar, detergent, and bleach have no odor.

 

Carbonated beverages release an odd, unnamable aroma.

 

Celebrations suffer as people can't smell birthday cake, pizza, even the stinky hallmark of Passover, gefilte fish.

 

Many people smell cigarette smoke, although none is around, or dirt, or the stench of rotten coffee grounds or moldy garlic.

 

Chefs can't smell their food. Runners can't smell their sweat. People fear they won't detect their house on fire.

Some people list the things they can smell, because these are far fewer than the odors that they can't detect.

 

Medicine has names for the disorders of olfaction. Anosmia is absence of the sense of smell, cacosmia the odor of rot, and phantosmia an "olfactory hallucination."

 

 

To continue reading, go to The Niche, where this post first appeared.

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She Had Her Own Mutation, Sequencing Led to a Treatment and Major Genetic Discovery – Then She Died of COVID

It isn't often that an investigation of a single patient who has a devastating, unrecognized disease leads to finding an existing drug that works, but also reveals something entirely new about gene function. A study from Dusan Bogunovic, PhD, Director of the Center for Inborn Errors of Immunity at the Icahn School of Medicine at Mount Sinai and colleagues just published in the journal Immunity, tells such a tale.

 

The young woman was only 18 when the investigation began. Her death from COVID-19 tragically juxtaposes the challenges of treating an ultrarare genetic disease with those of a pandemic infectious disease.

 

"We were so so sad when she passed. She was doing so well for the first time in her life for full 2 years. She was very happy, and her family was very happy to see her that way," said Dr. Bogunovic.

 

To continue reading, go to DNA Science, where this post first appeared.

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COVID Genomes Paint Portrait of an Evolving Pathogen

The COVID-19 pandemic is an unfolding story told in numbers. While news reports focus on the number of tests, cases, hospitalizations, and deaths undulating through time and space, an organization called the GISAID Initiative tracks the number of SARS-CoV-2 genome sequences that researchers have posted, from all over the world. It recently reached a milestone: 75,000.

 

Consulting genome sequences to follow and predict the spread of an epidemic or pandemic is called genomic epidemiology. It's important.

 

Public posting of the first genome of the novel coronavirus from researchers in China, back in early January, got the ball rolling in vaccine development. Some companies were able to plug the new genetic information into vaccine designs already in the works for other viruses.

 

To continue reading, go to DNA Science, where this post first appeared.

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Can Past Coronavirus Infection Protect Against COVID-19? Hints from Smallpox Vaccine

In ordinary times, a new report describing experiments on bits of smallpox scabs nestled in Civil War museum artifacts would have been mildly interesting. But these days, clues in old poxvirus genomes are especially intriguing because they may explain how some people resist COVID-19, perhaps thanks to a past run-in with a different coronavirus. According to another recently published study, these individuals haven't tested positive for COVID-19 or SARS or had contact with people who have, yet they have immune memory – T cells that recognize a coronavirus that infects bats.

 

Could exposure to one type of coronavirus protect against infection by another?

 

"The origins and genomic diversity of American Civil War era smallpox vaccine strains," published in Genome Biology, looks at a possible precedent to answer that question. Such cross-reactivity happens when an antibody or T cell recognizes a surface molecule common to more than one species of pathogen. It's a little like recognizing Eric Clapton in different bands.

 

A Brief History of Smallpox Vaccination

 

To continue reading, go to DNA Science, where this post first appeared.

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Vaccine ‘durability’: COVID-19 immunizations coming soon but will they last?

As the days unfold with a seeming sameness in this odd summer of the pandemic, news of vaccine clinical trials begins to trickle in, and another buzzword from epidemiology is entering the everyday lexicon: durability.

 

To be successful, a vaccine's protection must last or booster shots periodically restore it. Some vaccines lose efficacy over time, including those for yellow fever, pertussis, and of course influenza.

 

For some vaccines, antibodies and the B cells that make them persist and protect for a long time. For other infectious diseases, like TB and malaria, T cells are needed in vaccines too. B and T cells (lymphocytes) are types of white blood cells, which are part of the immune system.

 

Antibody response may be ephemeral

 

"Give a man a fish and you feed him for a day. Teach him how to fish and you feed him for a lifetime," said Chinese philosopher Lao Tzu, founder of Taoism.

 

Tzu might have been referring metaphorically to the immune system's response to viral infection: an initial rush of antibodies that fades as a longer-lasting cell-based memory builds that primes the body to rapidly release antibodies upon a future encounter with the pathogen.

 

 

To continue reading, go to Genetic Literacy Project, where this post first appeared.

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Rare genetic disorder homocystinuria can cause strokes, seizures and death. A ‘genetic glitch’ in blind cavefish offers hope for a treatment

The discovery of a gene behind the absence of eyes in Mexican cavefish may suggest a new way to treat a rare but debilitating disease in humans – homocystinuria.

 

In homocystinuria, deficiency of an enzyme (cystathionine beta-synthase a, or CBS), blocks the breakdown of two protein building blocks, the amino acids methionine and serine, while a third, cysteine, diminishes. An array of signs and symptoms result.

 

To continue reading, go to Genetic Literacy Project, where this post first appeared.

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Gastruloids Stand In for Early Human Embryos

Remember human embryonic stem (hES) cells? We don't hear much about them anymore. So I was surprised to see an application of the controversial cells to grow human embryo-like structures in a recent issue of Nature.

 

Human embryonic stem cells are not, and have never been, taken from human embryos. Instead, they're grown in laboratory glassware from cells that are sampled from the inner cell mass. The "icm" is the stage when the prenatal human is a smear of cells hugging the interior of a hollow ball of cells, the blastocyst. The icm expands and contorts, layering itself into embryohood, as the blastocyst gives rise to the nurturing extra-embryonic membranes.

 

In 2009 the National Institutes of Health issued guidelines forbidding researchers from using government funds to derive new hES cells, but the agency provides nearly 500 already-existing hES cell lines. They represent dozens of inherited diseases, from cancers to neurological conditions to connective tissue disorders – quite an eclectic list.

 

To continue reading, go to my blog DNA Science, where this post first appeared.

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A Tale of Two Clinical Trials: Gene Therapy for a Rare Disease and a Vaccine for COVID-19

Encouraging preliminary findings in a phase I clinical trial for a COVID-19 vaccine were widely reported as soon as the paper appeared in The New England Journal of Medicine July 14. Coverage of the recent deaths of two boys in a clinical trial to test a gene therapy for a rare, devastating muscle disease were more under-the-radar.

Comparing the two very different scenarios illuminates the scientific rigor behind the clinical trial process.

 

The boys had X-linked myotubular myopathy. MTM affects 1 in 50,000 male births. Seventy-five percent of boys die in weeks or months of respiratory failure; average life expectancy is 29 months. Given that prognosis, taking the risk of an experimental treatment in a clinical trial makes sense. Parents of participants as well as physicians know that children can die during the trial, due to the disease or to toxicity at higher doses of a treatment.

 

In contrast, volunteers in a clinical trial to evaluate a vaccine are healthy.

 

Although comparing MTM gene therapy and a COVID-19 vaccine is a bit of apples and oranges, those fruits are in the same bin in terms of progression through the three phases of development of a new treatment or preventative:

 

To continue reading go to my blog DNA Science, where this post first appeared. 

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