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Genetic Linkage

Why COVID Vaccines Proliferate as Monoclonal Antibody Drugs Fade

Monoclonal antibody drugs to fight COVID are being taken off the market while new COVID vaccines are arriving, even as the old ones are standing up quite well against new viral variants. How can two interventions that tweak an immune response have such different outlooks? It stems from the biology.

 

Understanding what antibodies are, how our bodies make them, and how vaccine and monoclonal antibody technologies work and differ, explains the distinction.

 

The Antibody Response is Naturally Polyclonal

 

The immune system is a vast army of cells and their secretions that recognize and respond to the presence of "non-self" cells and molecules, like the spike proteins that fringe SARS-CoV-2, the virus behind COVID. One of the first things I learned in college is that "biology is really chemistry," and that's certainly true for the immune response. It's all about recognizing molecules.

 

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

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COVID Virus Ventures Beyond the Lungs, Often Lodging in the Brain

COVID inflames blood vessel linings in the brain, but the virus also enters brain cells (NIH).

 

In early 2020, COVID appeared to be mostly respiratory, with blame for the shattering of delicate lung tissues initially placed on the violent "cytokine storms" unleashed from overactive immune responses. At first, autopsy series focused on the inflammation and antibodies, not finding evidence of the virus itself. But that view has changed.

 

As the fourth year of the pandemic dawns, a study published in Nature from Daniel Chertow, MD, MPH, head of the Emerging Pathogens Section at the NIH Clinical Center and colleagues, finds the virus in many body parts – particularly, the brain. The discovery may explain cases of long COVID.

 

Indirect Attack on the Brain

 

At first, researchers thought the role of the virus on the brain was indirect.

 

In July 2022, Avindra Nath, MD, clinical director of the National Institute of Neurological Disorders and Stroke and colleagues reported in the journal Brain changes in the brains of nine people who died quickly from COVID. Autopsies revealed antibodies glommed onto viral antigens on the tile-like endothelial cells that form the blood-brain barrier. As capillaries disintegrated, the risk of stroke skyrocketed amid catastrophic destruction.

 

The COVID-infected brain is a mess.

 

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

 

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On COVID Origin and Omicron Persistence: This Geneticist’s View

The latest phrase borrowed from biology in COVID conversations is convergent evolution. It refers to pairs of unrelated species that look similar because their ancestors evolved under similar environmental conditions. Natural selection favored adaptive (helpful) inherited traits, and millennia later, two unrelated species of mammals or birds look remarkably alike.

 

Convergent evolution happens to viruses, too. It is unspooling right now as SARS-CoV-2 genome evolution coalesces into variations on the Omicron theme.

 

The natural history of SARS-CoV-2 began with the wild type, another term from classical genetics. It means "most common," not "normal" as the media often misuses it.

 

As the virus changed, we grouped sets of new mutations, which substitute one RNA base of the genome at a time, into "variants." We named them, which biologists tend to do.

 

Alpha, recognized in November 2020, begat beta, gamma, and delta, all of which stayed with us for a bit. The next few versions were fleeting. The International Committee on Taxonomy of Viruses and WHO skipped Nu (because it sounds like "new") and Xi (a common surname), landing on Omicron. And natural selection has favored its collection of mutations. No new Greek letters necessary.

 

When Species Look Alike

 

Biologists term traits that are alike in two species that arise from recent shared ancestors homologous, while similar structures or behaviors that arise from similar environmental exposures are analogous. Convergent evolution reflects responses to similar environments (analogy), rather than descent from recent shared ancestors (homology).

 

Striking examples of convergent evolution are pairs of placental mammals and Australian marsupials. These include anteaters, moles, wolves, ocelots and native cats, flying squirrels and flying phalangers, and groundhogs and wombats.

 

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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From Doodle Dogs to COVID: On the Meaning of Wild Type

Zeke, shown here retrieving a stick from the surf at Lambert's Cove, Martha's Vineyard, is an aussiedoodle – a cross between an Australian shepherd and a poodle. I did an informal survey there over the course of a week, and estimated that approximately 70 percent of the dogs on the beach harbored poodle genes.

 

Diverse doodles share the trademark tight curly fur, but vary in size, color, head shape, and behavioral and other traits. Several websites list 50+ variations on the poodle hybrid theme, including the bassetoodle, bernedoodle, chipoo, doxiepoo, Irish doodle, poochon, rottle, and shihpoo.

 

Why poodles? The breed evokes such effusive descriptions as "confident yet affectionate, but also active and deceivingly athletic. What's not to like about the dignified and elegant Poodle?" The mixes are deemed highly intelligent, although I can't imagine any of my cats chasing a stick, let alone retrieving it.

 

Perhaps I was witnessing a biased sampling, and the doodles simply have a combination of gene variants that somehow makes them love running in the sand. I watched, transfixed, as a goldendoodle followed a seabird far out into the surf, upsetting the human observers and revealing a superior avian intelligence.

 

To continue reading, go to DNA Science, 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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Expand Rapid Testing to Help Counter COVID Variant Spread, Says Harvard Epidemiologist Michael Mina

I just returned from an enlightening trip to CVS, to photograph Abbott Lab's at-home rapid antigen test for COVID, BinaxNOW. It became available at three major drugstore chains on April 19.

 

"Do you have the rapid COVID test? The at-home one?" I asked the woman behind the pharmacy counter.

Deer-in-the-headlights.

 

Fortunately, the pharmacist behind her overheard. "Not only don't we have it, but we don't know when we'll be getting it." I wasn't too surprised; I live in a small town.

 

So I got on line to buy some vitamin gummies, appropriately socially distanced, and saw to my immediate left a prominent display of items that everyone should have to prevent COVID: wipes, hand sanitizer, gloves, masks. They provided a backdrop to a stack of 6 boxes of – BinaxNOW!

 

Of course, a detection test to see if you've been infected is not at all the same thing as a preventive measure. So I circled back to the pharmacy, and within seconds of notifying the pharmacist that the tests were indeed available, an angry summons for the manager bellowed out over the loudspeaker.

 

Oops.

 

 

To continue reading, go to DNA 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

(hVIVO)

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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‘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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