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Genetic Linkage

Do Shrinking Chromosomes Put Older People at Higher Risk of Severe COVID?

When a headline in the Washington Post dubbed COVID "A Plague of the Elderly," I cringed, envisioning Logan's Run, the sci-fi classic in which people past a certain age voluntarily die. The film came out in 1976, the year I graduated college.


That would make me, well, elderly.


Yes, older folks are over-represented among those who get very sick or die from COVID, with "nearly 9 out of 10 deaths now in people 65 or older," WaPo reminds us. That is striking for an age group that makes up only 16 percent of the population. But while media reports trumpet the damning statistics, few delve into the biology behind the elevated risk: it could be that our shorter chromosomes hamper the immune response.


The WaPo article, like others, states the obvious:

"The vulnerability of older people to viruses is neither surprising nor new. The more we age, the more we accumulate scars from previous illness and chronic conditions that put us at higher risk of severe illness."


Yes, a 75-year-old with COPD is less likely to survive COVID pneumonia than a 75-year-old with healthy lungs. And developing COPD is more likely after decades of exposure to irritants. But number of years by itself may be a surrogate for some other factor.

Might the culprit be telomeres, the tips of chromosomes? They shrink as time passes, like candles burning down.


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

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Ten Lessons from COVID: A Round-up of Experts

Planning for the next pandemic begins with acknowledging what we did wrong for COVID-19. As the situation has calmed, experts are weighing in on what we did, and didn't do, as the months unfolded. I've distilled and organized their comments from the medical literature and webinars. Several of the opinions are from Preventing the Next Pandemic: New Tools for Global Surveillance, which the Harvard T. H. Chan School of Public Health held for journalists October 17, 2022.


Next time, we should:


1. Recognize the field of ethics as practical, not just an academic discipline.
Determining the 'right' course of action in many circumstances proved more vexing and controversial than solving the technical challenges, such as developing vaccines and treatments, wrote Ezekiel Emanuel, Vice Provost for Global Initiatives at the University of Pennsylvania and colleagues, in The New England Journal of Medicine ("What COVID Has Taught the World About Ethics").


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

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The Utter Oddness of COVID Anosmia

The sudden inability to smell and taste that comes with COVID is startling and difficult to describe. I was lucky to experience it only for a few days.


Anosmia is the partial or total loss of the ability to smell, which vanquishes most of the sense of taste, too. The COVID version is more profound than the familiar dulling of the sense from the mucus of a common cold. And it has a different origin.


The odd part of COVID anosmia is that the virus alters gene expression in nerve cells in the nose – even though the virus can't actually enter nerve cells (neurons). Then the temporarily crippled cells can't signal the brain that the person is inhaling near the seashore or passing a garbage dump. Understanding the basis of the secondhand assault may clarify other puzzling effects of the changeling coronavirus – perhaps even long COVID.


Clever experiments recently revealed how COVID anosmia happens. Benjamin R. tenOever and colleagues from the NYU Grossman School of Medicine and Columbia University report their work using golden hamsters and the noses of human corpses in Cell.


First, a closer look at how the sense of smell works.


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

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SARS-CoV-2 Pops Up, Mutated, Beyond the Respiratory Tract

As if the waves of novel variants of "interest" and "concern" sweeping the planet haven't been enough, and we find versions of SARS-CoV-2 dodging in and out of species in a complex pattern of spillovers and spillbacks, we discover that it's even sneakier. Two new papers in Nature Communications, from a group at the Max Planck Bristol Centre of Minimal Biology, describe how the virus can differ genetically in different parts of the same host.


That may mean that if vaccines and treatments vanquish the virus in the respiratory tract, the pathogen might persist elsewhere. And the viruses in new places replicate and infect more vigorously, better able to elude our immune response. That's not good news as protection from vaccinations or having had COVID-19 wanes.


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

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Sandy From the Mountains Dies, Leaving a Message to the Unvaxxed

Five days ago, Sandy's husband allowed the staff in the ICU to turn off her life support, and COVID claimed yet another.


Sandy and her husband lived in a cabin nestled into a mountainside in a small town in the Rockies, next door to my daughter Sarah. I met Sandy last March, when Larry and I and our daughter Carly visited.


I'd heard about Sandy, how she helped Sarah deal with encroaching wildfires right after she moved in. But she wasn't what I expected.


Sandy looked younger than her 70+ years and remarkably like Stevie Nicks, pretty and vibrant and warm, with glimmering white-blond hair and beautiful permanent makeup that accentuated her eyes. She was owl-like. Her husband reminded me a little of a rumpled, flannel-shirted Eddie Vedder, or James Taylor with much better hair, an aging yet striking rock star couple.


We all clicked. Two friends dropped by, and we held an impromptu seder on that first night of Passover. We sang the traditional songs to our new Christian friends – Dayenu, Let My People Go – then inexplicably listened to Led Zeppelin's "Ramble On" playing on repeat.


It was exciting to gather after months of lockdown. Vaccination had just begun, and so my husband and I, our ages a risk factor, were the only ones who were fully protected. The neighbors weren't, tragically believing their isolation would keep them safe, although Sandy's husband went into town for work.


We all tried to warn them.


Sandy knew I was a biologist and wanted to know more about the vaccines, so I explained how they work. I told her that I couldn't imagine how a vaccine could be more harmful than the threat of what the virus could do. She asked insightful questions, many of them, but still looked skeptical.


And that triggered my younger daughter.


Carly tried to hold it in, but couldn't. And so she tearfully poured out what she had seen from her sixth-story window in Astoria, Queens during those horrid months as winter turned to spring in 2020, as the white-shrouded bodies were stacked up at the ambulance bay of the hospital right next door, like bleachers of death. It's an image she nor the rest of our family can never unsee.


But to Sandy, in her cabin in the woods, an inner city hospital must have seemed a million miles away. In March 2020, the mantra "it can't happen here" was still playing in many parts of the country.


Sandy remained unconvinced. Unvaxxed. I can only imagine where she got her information. Sarah persisted in offering to take her to get vaccinated, through the summer. But then Sandy cut her off completely over the issue, silencing Sarah's good intentions. Until that time, Sandy and I had talked and texted. We liked the same books, bands, and TV shows. We bonded. I considered her a friend.


Two weeks ago, Sandy got COVID. Her husband had brought it home.


I knew that Sandy wasn't stupid and that she knew biology – during the conversation on Passover she'd mentioned mitosis, cell structure, DNA. I see now that when it came to vaccination, she was simply scared. And her fear and denial cost her her life.


Statistics on the never-ending pandemic become obsolete almost as soon as they are compiled these days. It is undeniable that most COVID deaths are among the unvaxxed. There's no more hiding in the woods, especially now with omicron and its off-the-charts transmissibility.

Still, an astounding fifteen percent of the overall US population refuses vaccination, the percentages distributed unevenly among the states.


It is unfathomable to me that anyone could compare the graphs of hospitalizations for the protected versus the unprotected, the vaxxed a line hugging the X axis at the bottom and the unvaxxed a hockey stick of frightening exponential growth, and remain unconvinced.


I'll admit that I never saw this coming, the vaccine hesitancy that has catalyzed COVID, not only enabling a deadly virus but giving it room to evolve. The pandemic wasn't a surprise, as I suspect it wasn't to many other biologists. And I've always thought herd immunity – not a new idea – was more a theoretical ideal than an achievable goal in the real world. But I never imagined the politicization of a national public health crisis stemming from an infectious disease, nor the fear that spawns willful ignorance.


I'm trying now to understand why Sandy died, why she thought the government was trying to take away a "right" by offering, at no cost, something that could prevent her death. It's too late for Sandy, but perhaps someone will read this post and go roll up a sleeve. I can't wrap my head around the glaring fact that thousands have made the same stubborn choice as Sandy.


But Sarah found some closure the day after Sandy died, last Sunday. She and a friend were hiking in the spectacular mountains that are the backdrop to the log homes, some built onto cabins going back a century. She texted us images of a tree with a small, perfect, owl sitting on a lower branch.


"Last night! It was so beautiful, little, white, we got really close to her and she just stared right back for awhile. I know this sounds crazy but it felt like Sandy coming to see me! I really felt that and cried and said everything I wanted to say to Sandy, that I was sorry she was misled, sorry she suffered. And when I finished, she flew off."


So RIP Sandy from the Mountains who looked like Stevie Nicks.


"And I saw my reflection in the snow-covered hills
'Til the landslide brought me down."


May your story save lives. We have the tools to hold off the landslide.



Originally posted at my blog DNA Science at Public Library of Science.

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How Watson and Crick Predicted the Origin of Omicron and Laid the Groundwork for COVID-19 Vaccines

The tantalizing final sentence to James Watson and Francis Crick's landmark 1953 paper in Nature introducing the genetic material, DNA, is almost as famous as the report itself:


"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."


That copying mechanism gone awry spawns the mutations that create new viral variants.


Mutation, Natural Selection, and Recombination, Oh My!


Like Dorothy of Wizard of Oz fame exclaiming "lions and tigers and bears, oh my!" three major forces of nature set the stage for genome evolution: mutation, natural selection, and recombination.


The virus we're battling has a single strand of RNA for its genetic material, and not the more familiar double-stranded DNA. But an RNA genome must also replicate – copy itself – when one virus becomes two. And mistakes, mutations, can happen when they do so, like perpetuating a typo when copying a document.


"Every chance a virus has to replicate it can come up with a new strategy to evade the immune system," said Bruce Walker, MD, Director of the Ragon Institute of MGH, MIT and Harvard, at a recent press briefing of the Massachusetts Consortium on Pathogen Readiness (MassCPR). That's too teleological an explanation for me – a virus doesn't intentionally change itself into a fitter form. Instead, mutations tend to arise at genome locations where the sequence is repetitive, like CGCGCGCG compared to ACGCCUCGAU. It's easier to mistype when "the" is next to "they" in a document, compared to "hippopotamus" next to "diarrhea."



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

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A lucky segment of the population is genetically immune to the COVID virus. What can we learn from them?

In March 2020, Eleanor A. had been sick for several days. Thinking it might be the new respiratory illness going around, she called her internist, who sent her for a COVID-19 test. She was positive. "Results didn't come back for six days, and Jesse and I shared a bed and bathroom during that wait time," she recalled. Both are in their 80s. 


Eleanor's case was harrowing, but fortunately she didn't need to be hospitalized. "I experienced overwhelming fatigue for much of the next ten days. I slept a lot. One night I got up and felt disoriented, hot and cold at the same time, and very unstable. I thought I wouldn't make it to the bathroom or back to bed. I kept calling for Jesse, but he was sound asleep and never heard me."


Fatigue and shortness of breath persisted. Scans revealed lung scarring, but Eleanor slowly recovered.


Through it all, Jesse never had a sniffle, cough, throat scratch or fatigue. Although he'd been beside his wife as the virus invaded her body for days, he never got sick. Later, his blood showed no antibodies against SARS-CoV-2, the virus that causes COVID. That meant that unlike people who are infected but then shake off the virus without getting sick, Jesse wasn't infected in the first place.


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

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How Viral Variants Arise

The public has had a crash course in virology. But sometimes media coverage spews jargon so fast, often without definitions or descriptions, that I wonder to what degree readers or viewers know what terms like antibody, cytokine, or mRNA actually mean.


"Variant" is especially problematical, when coming after "viral," because it has a plain language meaning too – variation on a theme, something just a little bit different from what we're used to. But during an epidemic, a small genetic change can have sweeping consequences, fueling a pandemic.


Mutations Build Variants

Variants of SARS-CoV-2 – the COVID virus – are sets of mutations. A mutation is a specific change in a specific gene.


Different variants have some mutations in common, so it can get confusing. For example, three variants circulating in India each has 6 or 7 mutations, three in common. The first and second variants that were discovered each has a unique mutation, but the third variant is a subset of parts of the first two. Got that?


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

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Would you agree to be infected with COVID for science? Intentional 'challenge' studies underway as researchers explore new vaccines and treatments


Lauren Thomas, who just turned 26, is trying to get into a clinical trial at the University of Oxford, where the American is in a master's program in data science. She's seeking to be intentionally reinfected with SARS-CoV-2, the virus that caused her bout with COVID-19 back in October.


Thomas had a mild case – just a fever. So now she's volunteering to help researchers understand the aftermath of infection, waiting to hear whether she'll get into the clinical trial. In the meantime, she's an organizer for 1daysooner, a non-profit advocacy group for people wishing to participate in research and launched in April 2020. A major focus has been joining clinical trials for COVID vaccines.


Why would anyone sign up for a second encounter with the virus that has shattered the world?


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

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3 Possible Origins of COVID: Lab Escapee, Evolution, or Mutator Genes?

B.1.1.7 variant (NIAID)

"Virus outbreak: research says COVID-19 likely synthetic," shouted the headline in the Taipei Times on February 23, 2020. The idea that the novel coronavirus SARS-CoV-2 arose in a virology lab in China – by accident or as a bioweapon – has sparked an undulation of accusation and explanation ever since.


The latest chapter: An "open letter" in the April 7, 2021 New York Times, calling for "a full investigation into the origins of COVID-19." The two dozen scientists who signed the letter cite the continuing absence of a "robust process" to examine critical records and biological samples. Their argument responds to the WHO's March 20 press event that barely considered an origin other than from a natural spillover.


But two types of new information may counter the lab escapee hypothesis: filling-in-the-blanks of mammals that may have served as "missing links" in the evolution of disease transmission, and the rapid rise of viral variants reflecting a tendency to mutate that may underlie SARS-CoV-2 seemingly bursting from out of nowhere.


So here is my view, as a geneticist, of three possible origins of SARS-CoV-2:


1. Bioweapon – an engineered pathogen or escape of a natural candidate


2. Gradual evolutionary change through intermediate animal hosts, mutating along the way and becoming more virulent


3. "Mutator" genes that trigger mutations in other genes, speeding evolution


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

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