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Genetic Linkage

Why Do Males Fare Worse With COVID-19? A Clue From Calico Cats

Early on in the pandemic, a worse clinical scenario for the male of the species emerged. A study published mid-May from Italian researchers offered early statistics from the WHO and Chinese scientists: a death rate of 1.7% for women and 2.8% for men. Then Hong Kong hospitals reported that 15% of females and 32% of males with COVID-19 needed intensive care or had died.

 

In July a Perspective published in Nature Reviews Immunology from researchers at Johns Hopkins University and the University of Montreal noted a similar "male bias" for other viral infections, including SARS and MERS. By then, the wide community testing in South Korea and data from the U.S. indicated 1.5-fold higher mortality for men for COVID-19. The pattern repeated in 38 countries, for patients of all ages.

 

Now a new study published in Nature Communications expands the increased risk for those who have only one X chromosome

 

To continue reading, go to my DNA Science blog at Public Library of Science.

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Worse Than COVID? The Tasmanian Devil’s Contagious Cancer

It's hard to imagine anything worse than the horrors at our hospitals right now. But in a recent JAMA webinar, Nicholas Christakis, Yale Sterling Professor, put the fatality rate of COVID-19 into historical perspective:

 

"Bad as it is, the fatality rate, at .5-.8%, isn't as bad as bubonic plague, which would kill 50% of a population in a few months. Or Ebola at 80%. Or smallpox at 95%. It could have been so much worse." He's a physician, scientist, public health expert, and sociologist.

 

It's an unusual viewpoint to downplay the horror of this moment in time, but Dr. Christakis's new book, "Apollo's Arrow: The Profound and Enduring Impact of Coronavirus on the Way We Live," takes a broader look. He said at the webinar:

 

"This way we're living right now seems alien and unnatural, but plagues aren't new to our species, just new to us. People have struggled with plagues for thousands of years. The Iliad opens with a plague on the Greeks and Apollo reigns down, the Bible, Shakespeare. What's different about our current experience is our time in the crucible happens to be occurring when we can create a vaccine in real time. The fact that we have the technological capability to respond within a year with phase 3 trials of active agents is mind-boggling."

 

We aren't the only species subject to unseen pathogens, including the viruses that aren't even cells or technically alive, just borrowed bits of our own genomes turned against us. With Dr. Christakis's wider view in mind, I noticed a new article about an infectious cancer in Tasmanian devils. It combines two terrors.

A Transmissible Cancer

 

 

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

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Dr. Paul Offit Talks COVID Vaccines, With JAMA’S Howard Bauchner

Science and medical writers have been under an avalanche of information for nearly a year now, as we translate technical information about COVID-19 for the public. Links to the latest journal articles overload our inboxes, but, at the beginning and now during another surge, tracking down experts to interview has been difficult. They're simply too busy saving lives.

 

A critical resource for me has been the series of JAMA Live Q+A webinars for the media hosted by Howard Bauchner, editor-in-chief of the Journal of the American Medical Association. It is wonderful to hear the top clinicians and researchers speak freely, at length, and in context, or meander – a nice contrast to the echoing soundbites of mainstream media.

 

JAMA webinar speakers have included the career scientists who've already led us through the waters of HIV/AIDS, hepatitis, influenza, Ebola, zika, SARS, and other epidemics and pandemics. Anthony Fauci is a frequent guest – I wrote up his talk with FDA's Peter Marks here.

 

The webinars also feature the young clinicians battling our new enemy. Early on, Maurizio Cecconi's session, "Coronavirus in Italy: Report From the Front Lines," brought me to tears. The head of the Anaesthesia and Intensive Care Department at Humanitas Research Hospital in Milan, Dr. Cecconi described, at the webinar and in a report (both accessible here), the admission of "patient zero" to the ICU in Lombardy, on February 20, 2020, and how his infection was traced to a local friend who'd had contact with an infected person from China. The 38-year-old was initially not very ill and partied a lot. And the rest is medical history.

 

Recently Dr. Bauchner spoke with Paul Offit, who directs the Vaccine Education Center and is an attending physician in the Division of Infectious Diseases at Children's Hospital of Philadelphia. He's on the FDA Advisory panel that will meet December 10 to discuss Pfizer's COVID-19 vaccine and on the 17th to consider Moderna's.

 

Dr. Offit is best known for co-inventing a vaccine against rotavirus, a diarrheal disease that has claimed millions of lives. It became available in the US in 2006, and is on the World Health Organization's list of essential medicines. The clinical trials for the rotavirus vaccine RotaTeq took four years and involved 70,000 participants – much more typical than the lightning speed of the COVID vaccine trajectory.

 

Here's the Q+A from December 2, lightly edited, with my explanations in parentheses. I've omitted the discussion of who gets vaccine when – that's all over the news.

 

To continue reading, go to my blog DNA Science at Public Library of Science.

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T Cells May Tell Us More About COVID Immunity

While antibodies have been the focus of testing for past infection with COVID-19, T cells will also provide some insights -- potentially better ones, experts say.

 

These lymphocytes are the first responders that then coordinate the immune response while building an imprint, a memory, so that subsequent infections fade quickly, often unnoticed.

 

T cell tests are more complex and typically reserved for research, but some may be coming to the clinic soon, with at least one company seeking FDA emergency use authorization (EUA). Recent studies indicate that assaying T cells can even improve diagnostic accuracy and possibly predict how COVID-19 will unfold.

 

"Testing T cell responses can accelerate detection of an infection by as much as a week. The cells come in on day 2 and they divide very quickly, to detectable levels as early as 3 or 4 days from infection," said Dawn Jelley-Gibbs, PhD, who investigated T cells in influenza at the Trudeau Institute in Saranac Lake, New York.

 

"Identifying people who have been infected and become immune could have huge benefits for enabling society to safely return to normalcy. Numerous antibody tests exist, but doubts remain about their reliability and about antibody longevity post-infection," said Maria Oliver, PhD, senior scientist at Indoor Biotechnologies in Great Britain, one of several companies developing clinical T cell tests.

 

T Cell Basics

 

To continue reading, please go to MEDPAGE TODAY, where this post first appeared.

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Genetic Clues in the Goop of a COVID Swab

(U.S. Marine Corps photo by Cpl. Sarah Marshall)

The components of certain things are meant to remain mysterious. The ingredients of sausage. A burger's slimy secret sauce. The recipe for Coke or Kentucky Fried Chicken.

 

Researchers from Stanford University are tackling the make-up of another entity, something rather new to our world: the stuff retrieved from swabs shoved up nostrils to sample genetic material from SARS-CoV-2, the virus behind COVID-19. A swab actually samples much more than the virus's RNA, required for diagnosis.

 

Super Swabs

 

John Gorzynski and colleagues describe the "multi-omic data repositories" from deployed swabs in a preprint (not yet peer-reviewed) and at the recent virtual annual meeting of The American Society of Human Genetics.

"A single nasopharyngeal swab can reveal substantial host and viral genomic information in a high-throughput manner that will facilitate public health pandemic tracking and research into the mechanisms underlying virus-host interactions," they write.

 

That's a mouthful. I'll just call them super swabs.

 

Amplifying Viral Sequences

 

Extracting clues from the stuff on the swabs is a little like collecting evidence at a crime scene. Several things happen.

 

To continue reading, please go to my blog DNA Science at Public Library of Science, where this post first appeared.

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Can Some Antibodies Worsen COVID-19? The Odd Situation of Enhancement

Antibodies are supposed to be the good guys. The proteins, built of distinctive Y-shaped pieces, enter the bloodstream early in infection, pouring out from plasma cells. They then latch onto molecules festooning pathogens and alert natural killer cells, which release a torrent of cytokines and complement, which are the biochemical weapons of an immune response.

 

Fighting infection is a complex business.

 

In a mysterious phenomenon called "antibody-dependent enhancement," the proteins actually make matters worse, intensifying symptoms. When a vaccine elicits the errant antibodies, the backfiring is called "vaccine enhancement of disease." We know these reactions exist, but still do not completely understand them.

 

The turncoat antibodies can be coaxed to appear in test tube experiments, but are elusive in a patient who is getting sicker. That is, there's no clinical way to distinguish antibody-dependent enhancement from just a severe case of an infectious disease. And that can complicate analysis of a candidate vaccine. "Vaccine enhancement of disease" would show up in a clinical trial as more people receiving a vaccine getting sick than the participants getting placebo.

 

Reportedly that hasn't happened for the candidate COVID-19 vaccines, but the data won't be published until the phase 3 trials are completed.

 

To continue reading, please go to my blog DNA Science at Public Library of Science. 

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‘Challenge studies’: Should we be testing COVID vaccines by intentionally infecting volunteers?

To those who've never thought about volunteering to be intentionally infected to test a vaccine, the idea may at first seem a bit bonkers. But such "challenge" studies not only have a rich history, but nearly 40,000 people have already checked the box "I am interested in being exposed to the coronavirus to speed up vaccine development" at 1daysooner, a website and non-profit organization that launched in April.

 

Challenge studies go by other names: "controlled human infection models," "human viral challenge," and "purposeful infection." Dripping virus-tainted saltwater into a volunteer's nostrils enables researchers to track infection, and the immune system's response to it, right from the start. The approach complements phase 3 clinical "field" trials of efficacy that await natural infection in the community.

 

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

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5 COVID-19 Updates: Cats, Kids, Seniors, Blood, and an Old Vaccine

Times have been strange for us all, weird indeed for science journalists.

 

The initial manageable flow of news alerts to the media back in January quickly became an unceasing torrent. Every day now I receive dozens of news releases and heads-ups from science and medical journals. Many papers are preprints (not yet peer-reviewed) or embargoed, meaning we agree to not report findings until a certain date and time.

 

This is COVID article #42 for me. Today's post covers 5 news releases that seemed intriguing. Cats first!

 

Cats Get COVID From Owners

 

When four-year-old Negrito's human died of COVID-19, relatives took in the bereft European/Persian mix, who lived in Barcelona. Then Negrito developed difficulty breathing, so the new owners, who also had COVID, took him to the vet. Negrito's shortness of breath was due to an enlarged heart from a pre-existing condition, and he humanely crossed the rainbow bridge. But his bloodwork revealed a low viral load of SARS-CoV-2, although the cat had no other symptoms of COVID-19.

 

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

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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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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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