Could Genetics Be the Key to Never Getting the Coronavirus?
I may be talking too soon but I have a hunch that I might be one of those who do not catch Covid. I have had no version of it so far and I do have an unusually good immune system. With a bit of help it even defeated a bout of stomach cancer
Last Christmas, as the Omicron variant was ricocheting around the United States, Mary Carrington unknowingly found herself at a superspreader event—an indoor party, packed with more than 20 people, at least one of whom ended up transmitting the virus to most of the gathering’s guests.
After two years of avoiding the coronavirus, Carrington felt sure that her time had come: She’d been holding her great-niece, who tested positive soon after, “and she was giving me kisses,” Carrington told me. But she never caught the bug. “And I just thought, Wow, I might really be resistant here.” She wasn’t thinking about immunity, which she had thanks to multiple doses of a COVID vaccine. Rather, perhaps via some inborn genetic quirk, her cells had found a way to naturally repel the pathogen’s assaults instead.
Carrington, of all people, understood what that would mean. An expert in immunogenetics at the National Cancer Institute, she was one of several scientists who, beginning in the 1990s, helped uncover a mutation that makes it impossible for most strains of HIV to enter human cells, rendering certain people essentially impervious to the pathogen’s effects. Maybe something analogous could be safeguarding some rare individuals from SARS-CoV-2 as well.
The idea of coronaviral resistance is beguiling enough that scientists around the world are now scouring people’s genomes for any hint that it exists. If it does, they could use that knowledge to understand whom the virus most affects, or leverage it to develop better COVID-taming drugs. For individuals who have yet to catch the contagion—a fast-dwindling proportion of the population—resistance dangles “like a superpower” that people can’t help but think they must have, says Paula Cannon, a geneticist and virologist at the University of Southern California.
Like any superpower, though, bona fide resistance to SARS-CoV-2 infection would likely “be very rare,” says Helen Su, an immunologist at the National Institutes of Allergy and Infectious Disease. Carrington’s original hunch, for one, eventually proved wrong: She recently returned from a trip to Switzerland and found herself entwined with the virus at last. Like most people who remained unscathed until recently, Carrington had done so for two and a half years through a probable combination of vaccination, cautious behavior, socioeconomic privilege, and luck. It’s entirely possible that inborn coronavirus resistance may not even exist—or that it may come with such enormous costs that it’s not worth the protection it theoretically affords.
Of the 1,400 or so viruses, bacteria, parasites, and fungi known to cause disease in humans, Jean-Laurent Casanova, a geneticist and an immunologist at Rockefeller University, is certain of only three that can be shut out by bodies with one-off genetic tweaks: HIV, norovirus, and a malaria parasite.
The HIV-blocking mutation is maybe the most famous. About three decades ago, researchers, Carrington among them, began looking into a small number of people who “we felt almost certainly had been exposed to the virus multiple times, and almost certainly should have been infected,” and yet had not, she told me. Their superpower was simple: They lacked functional copies of a gene called CCR5, which builds a cell-surface protein that HIV needs in order to hack its way into T cells, the virus’s preferred human prey. Just 1 percent of people of European descent harbor this mutation, called CCR5-Δ32, in two copies; in other populations, the trait is rarer still. Even so, researchers have leveraged its discovery to cook up a powerful class of antiretroviral drugs, and purged the virus from two people with the help of Δ32-based bone-marrow transplants—the closest that medicine has come to developing a functional HIV cure.
The stories with those two other pathogens are similar. Genetic errors in a gene called FUT2, which pastes sugars onto the outsides of gut cells, can render people resistant to norovirus; a genomic tweak erases a protein called Duffy from the walls of red blood cells, stopping Plasmodium vivax, one of several parasites that causes malaria, from wresting its way inside. The Duffy mutation, which affects a gene called DARC/ACKR1, is so common in parts of sub-Saharan Africa that those regions have driven rates of P. vivax infection way down.
In recent years, as genetic technologies have advanced, researchers have begun to investigate a handful of other infection-resistance mutations against other pathogens, among them hepatitis B virus and rotavirus. But the links are tough to definitively nail down, thanks to the number of people these sorts of studies must enroll, and to the thorniness of defining and detecting infection at all; the case with SARS-CoV-2 will likely be the same. For months, Casanova and a global team of collaborators have been in contact with thousands of people from around the world who believe they harbor resistance to the coronavirus in their genes. The best candidates have had intense exposures to the virus—say, via a symptomatic person in their home—and continuously tested negative for both the pathogen and immune responses to it. But respiratory transmission is often muddied by pure chance; the coronavirus can infiltrate people silently, and doesn’t always leave antibodies behind. (The team will be testing for less fickle T-cell responses as well.) People without clear-cut symptoms may not test at all, or may not test properly. And all on its own, the immune system can guard people against infection, especially in the period shortly after vaccination or illness. With HIV, a virus that causes chronic infections, lacks a vaccine, and spreads through clear-cut routes in concentrated social networks, “it was easier to identify those individuals” whom the virus had visited but not put down permanent roots within, says Ravindra Gupta, a virologist at the University of Cambridge. SARS-CoV-2 won’t afford science the same ease of study.
A full analogue to the HIV, malaria, and norovirus stories may not be possible. Genuine resistance can manifest in only so many ways, and tends to be born out of mutations that block a pathogen’s ability to force its way inside a cell, or xerox itself once it’s inside. CCR5, Duffy, and the sugars dropped by FUT2, for instance, all act as microbial landing pads; mutations rob the bugs of those perches. If an equivalent mutation exists to counteract SARS-CoV-2, it might logically be found in, say, ACE2, the receptor that the coronavirus needs in order to break into cells, or TMPRSS2, a scissors-like protein that, for at least some variants, speeds the invasive process along. Already, researchers have found that certain genetic variations can dial down ACE2’s presence on cells, or pump out junkier versions of TMPRSS2—hints that there could be tweaks that further strip away the molecules. But “ACE2 is very important” to blood-pressure regulation and the maintenance of lung-tissue health, said Su, of NIAID, who’s one of many scientists collaborating with Casanova to find SARS-CoV-2 resistance genes. A mutation that keeps the coronavirus out might very well “muck around with other aspects of a person’s physiology.” That could make the genetic tweak vanishingly rare, debilitating, or even, as Gupta put it, “not compatible with life.” People with the CCR5-Δ32 mutation, which halts HIV, “are basically completely normal,” Cannon told me, which means “HIV kind of messed up in ‘choosing’ CCR5.” The coronavirus, by contrast, has figured out how to exploit something vital to its host—an ingenious invasive move.
The superpowers of genetic resistance can have other forms of kryptonite. A few strains of HIV have figured out a way to skirt around CCR5, and glom on to another molecule, called CXCR4; against this version of the virus, even people with the Δ32 mutation are not safe. A similar situation has arisen with Plasmodium vivax, which “we do see in some Duffy-negative individuals,” suggesting that the parasite has found a back door, says Dyann Wirth, a malaria researcher at Harvard’s School of Public Health. Evolution is a powerful strategy—and with SARS-CoV-2 spewing out variants at such a blistering clip, “I wouldn’t necessarily expect resistance to be a checkmate move,” Cannon told me. BA.1, for instance, conjured mutations that made it less dependent on TMPRSS2 than Delta was.
https://dnyuz.com/2022/07/25/could-genetics-be-the-key-to-never-getting-the-coronavirus/
************************************Time to question Australia's pandemic response
Tell me how this ends? This question was posed in 2003 by General David Petraeus during America’s invasion of Iraq, and it cut to the dead heart of that catastrophic campaign.
It’s a handy mental tool for probing almost any public policy so let’s apply it to the latest spike in cases of COVID-19.
Unsurprisingly, it has prompted another epidemic of “expert” demands for yet more overweening government intervention in the lives of the vast majority who have nothing to fear from this disease. And, given the mob has now worked that out, the only argument for mask mandates is to protect the hospital system.
Cast your mind back to 2020 when the first lockdowns were imposed, expressly for the purpose of preparing the hospital system for the pressure that was bound to come. Then, we were assured, intensive care capacity would be buttressed, so it could be surged to more than 7000 beds.
And yet, 18 months into the pandemic, it emerged that hospitals in states such as Western Australia, Queensland and South Australia could not cope with even routine demand. Maybe that’s because the number of acute care beds in Australia has more than halved in the last 28 years.
That is a reason to change negligent governments, not licence for politicians and health bureaucrats to impose restrictions on populations to mask their breathtaking decades-long incompetence.
Exactly a year ago, this column said that, soon enough, the great lie at the heart of Australia’s COVID-19 elimination strategy would be revealed because “the disease can’t be eliminated”. It was the only rational conclusion and yet, at the time, a parade of luminaries were still clinging to the intellectual corpse of COVID-zero and those arguing against it were vilified.
In August 2021, the best minds in New Zealand’s health system decided the COVID elimination strategy could be continued indefinitely and Prime Minister Jacinda Ardern declared it “a careful approach that says, there won’t be zero cases, but when there is one in the community, we crush it”.
Pause for a moment and consider the staggering stupidity of that statement in hindsight. But the point here is, the “expert” advice was self-evidently ridiculous at the time. Just three months later, after Ardern crushed her people and not the disease in a seven-week lockdown, she accepted the bleeding obvious: that not even a plucky island nation at the end of the world could live in isolation forever.
The Chinese Communist Party has soldiered on with COVID-zero and the despotic lockdown regime it exported along with the disease. Predictably, China’s economy has tanked and the misery the party has inflicted on its people is beyond measure. Perhaps the best result of that is it has prompted even the CCP cheer squad at the World Health Organisation to question its wisdom.
In May, Mike Ryan, the WHO’s emergencies director, made the startling observation that the effect of a “zero COVID” policy on human rights needed to be taken into consideration alongside its economic effect.
Parts of the city went into lockdown from March 28 before city-wide restrictions were indefinitely extended on April 5 in response to the number of COVID cases.
“We need to balance the control measures against the impact on society, the impact they have on the economy, and that’s not always an easy calibration,” he said.
Some have argued that those considerations had to be at the heart of the response from the outset and that the cure imposed risked doing more damage than the disease. Too often the Australian solution punished the many for the few. It preferred the very old over the young, reversing the risk equation most societies wager is the best way to protect their future.
So, the answer to the Petraeus question on coronavirus is clear and has been for more than a year. This only ends with Australian governments lifting all restrictions and actually learning to live with COVID-19 as just one more risk in a dangerous world. It is a decision other nations, such as Sweden and Norway, have already taken.
This is not, as eejits [idiots] would have it, “letting the virus rip”. To claim that is to wilfully ignore that we have endured more than two years of their miserable prescriptions racking up a taxpayer-funded bill probably somewhere north of $500 billion to keep the economy on life support and hit a vaccination rate of more than 95 per cent, precisely to prevent the virus from ripping through the community.
So now it is past time to ask another question: Where is the royal commission into the pandemic? This was a once-in-a-century moment that left no one unaffected, so there is no argument against holding the most rigorous test of how this nation fared.
It demands a panel of the best minds we can assemble to look dispassionately at what happened, how we responded, how we succeeded and where we failed. All Australian governments should participate and offer every assistance.
They have nothing to fear but the truth.
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Also see my other blogs. Main ones below:
http://edwatch.blogspot.com (EDUCATION WATCH)
http://antigreen.blogspot.com (GREENIE WATCH)
http://pcwatch.blogspot.com (POLITICAL CORRECTNESS WATCH)
http://australian-politics.blogspot.com/ (AUSTRALIAN POLITICS)
http://snorphty.blogspot.com/ (TONGUE-TIED)
https://immigwatch.blogspot.com/ (IMMIGRATION WATCH)
https://awesternheart.blogspot.com/ (THE PSYCHOLOGIST)
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