Gene linked to long Covid found in analysis of thousands of patients
nature.com
nature.com
Preprint is at https://www.medrxiv.org/content/10.1101/2023.06.29.23292056v... .
A link to the UCSC genome browser of the location of the SNP : https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=ch...
The location in question is upstream of FOXP4 and in an intron of two genes: FOXP4-AS1 and LINC01276
Global 16326 G=0.95075 C=0.04925
European 12074 G=0.97896 C=0.02104
African 2816 G=0.9052 C=0.0948
Asian 108 G=0.630 C=0.370
Unrelated, you may have some increased risk for prostate cancer: https://www.snpedia.com/index.php/Rs1983891
Plus modern tests can sample hundreds of gene in one batch. So they will only become better as time goes on, as more linked genes are discovered.
Depends on things like other risk factors, though. And like you say, if you can isolate ten genes that each have a similar effect, then you're getting somewhere.
The percentage variant, in contrast, is indeed ambiguous, the "60% increase" mentioned in the comment I responded to ironically only being unambiguous because the purely multiplicative interpretation (going to 60% of the value) would be a decrease. Such ambiguous use of percentage changes is common and annoying, and it would be good to see more use of the unambiguous "x-fold increase" wording.
[1] https://www.collinsdictionary.com/dictionary/english/fold-in...
https://en.wikipedia.org/wiki/Fold_change
In which case a 60% increased probability is a very significant increase. Seems like a valid thing to test for when assessing someone for long COVID, given it still remains somewhat of a diagnosis of exclusion.
but not really. what you're seeing is that some fraction of the populace is susceptible to long covid (risk factor or genetic).
Consider a 140% increase. Or a 1400% increase. It’s a bit hard to internalize what those mean.
2.4x and 15x is easier
George Bush (junior) signed a law barring insurance companies from using DNA data for health insurance pricing etc.
I was surprised by this b/c my assumption was that insurance companies would want that and Republicans would push for it. The law passed 95-0 in the Senate though so this seems like, along with robocalls, something everyone is opposed to.
Source: https://en.wikipedia.org/wiki/Genetic_Information_Nondiscrim...
Other forms of insurance, such as life or disability, can deny you coverage based on having had genetic testing.
The traditional view of Republicans being pro big business and Democrats fighting for the little guy don’t seem at all accurate in this day.
In the day of George W Bush, when this was passed?
The insurance industry as a whole is relatively familiar with the law, but some employers at large are less familiar and find themselves on the wrong end of enforcement actions with EEOC: https://www.eeoc.gov/data/genetic-information-non-discrimina...
Here's my genome: https://my.pgp-hms.org/profile/hu80855C Let me know if you can actually find anything interesting- the last time it was analyzed the genetic counsellors said I had no known genetic risks.
Today pretty much every baby born has their DNA taken and that can end up being used by law enforcement, but adults can try to avoid giving their DNA to the government, drug makers, and data brokers by not using services like Ancestry.com and 23andMe.
It's great that there is progress towards better diagnosis.
For example, herpes viruses. They are widespread and likely cause any number of health problems that are hard to disentangle.
I'd guess poor gut microbiomes and sleep disordered breathing caused by poor jaw development and nasal breathing issues to be far more common causes of fatigue and depression.
But yeah, science is slowly waking up to the fact that turns out that psychiatric conditions are, after all, caused by physiological factors in way more cases than we used to think.
If the downsides outweigh the upsides, why aren't we just eliminating them, as we have done for more deadly viruses like smallpox and polio?
- We don't have an effective vaccine yet, let alone one that is sterilizing.
- More than half of the population has HSV-1.
- HSV-1 lies dormant then reactivates and sheds, often asymptomatically.
It's unclear how you'd eradicate it, given these facts.
What is stopping modern medicine from engineering a competitive virus/bacteria/fungi that lurks about nerve bundles, attacks the herpes virus, and self-deprecates itself after.
Yes, living things are amazing, but any designer approaching even basic levels competence factors in repairability and serviceability.
So all that is to say: It's crazy complex and any single thing is liable to have myriad first order, second order, third order...30th order negative effects.
Here's what stopping modern medicine from doing that: 1) we don't know how to make what you describe 2) if we did, we don't know if it would be safe to put in humans 3) the consequences getting this wrong could be very severe 4) getting such a thing approved would be nearly impossible because we have no idea how to evaluate something like this.
It's not from lack of imagination- even if you solved the technical difficulties (which are copious), there would still be huge regulatory burdens to overcome (which are even harder to overcome than medical research).
With that said, we've already done similar things with lentivirus, https://en.wikipedia.org/wiki/Lentiviral_vector_in_gene_ther... but one side effect is cancer, another being complex immune system reactions. Lentivirus are useful because they can invade non-dividing cells, for example nerve cells aren't dividing, which means most viruses won't target them.
I worked in this field for a few decades but it was all wasted time. Nobody is going to support you working on a research project like this.
[1]: https://www.nih.gov/news-events/news-releases/nih-launches-c...
Thats easier to achieve.
It is also a symptom of pneumonia.
I had COVID, back before it was fashionable (February, 2020). It took me 10 months to feel normal again (the acute symptoms lasted 2 weeks. I hadn’t been that sick in decades).
Fatigue figured prominently. While I was experiencing acute symptoms, getting up to go to the bathroom basically finished my day.
I thought I had pneumonia, and the really scary stuff stopped, just before I was going to go to hospital. Thank Cthulhu I didn’t go. They would have killed me, and I would have infected a lot of people (as it was, all my family and friends got it. Share, and share alike).
I'm curious about this. Could you share more?
Is there evidence that hospitalization with COVID worsened the outcome?
As background, my father was hospitalized with COVID and passed away.
Apparently, this was the worst thing you could do.
You say that as if there is a just one doctor running one hospital in the entire world. I'm also aware the CDC gives advice but was this part of it?
It was what it was, and it is, what it is.
Still here, and still breathing, so that's a win, in my column.
Then when asked why you would have died you said "In the early days, they jammed you onto a respirator. Apparently, this was the worst thing you could do."
Are you not implying doctors at hospitals were acting against your best interest? Specifically the use of "they" instead of saying "it would have killed me" (as in going to the hospital)
Considering that diseases which spread through the air existed long before Covid wouldn't it be obvious that hospitals would be properly set up to isolate patients and avoid infecting visitors and people at the hospital for other reasons?
[1]https://www.csemag.com/articles/why-indoor-air-quality-matte...
More details: https://www.nature.com/articles/s41579-022-00846-2
Recovery seems to be in the first year or not at all. “As soon as it’s 12 months, it plateaus,” says study co-author Tala Ballouz, an epidemiologist at the University of Zurich in Switzerland. “You have a higher chance of recovery during the first year, and after one year it really becomes more of a chronic condition.”[1]
The incidence is estimated at 10–30% of non-hospitalized cases, 50–70% of hospitalized cases, and 10–12% of vaccinated cases.
Since roughly everyone should be expected to become infected, doesn't this mean that 10-30% of the population would have had, or should expect to get, Long COVID?
That just doesn't tally with what you see out in the world.
The term Long Covid (shortened here to "LC") covers an array of symptoms and severities. For example, depending on who's defining the duration, if after infection you feel light fatigue for 3 months and it then goes away, you've had LC. Most people I interact with have no idea I've been experiencing LC for a year. I know what it's done to my stamina, but they usually don't.
Right. That can start to reconcile things. But it is not only not visible from afar, but nor is it reported in smalltalk.
> [LC] covers an array of symptoms and severities
I'm fully behind the need to break down the array and make it studyable.
But, unless you net in a sizeable cohort for whom the symptoms were ultimately transient, barely noticed, or successfully managed by the sufferer, it simply can't stack up with the reality of life.
I'm aware that headlines generate $$$ for research, but 10-30% means it has to be ascribed to marketing over science. It's essentially an irrelevant figure in serious any analysis.
> I've been experiencing LC for a year
Right. And it is that long tail of high-severity/low-incidence research should focus. But here we're talking about 0.1% of the 10-30%.
I imagine whether you hear it in smalltalk varies a lot by peer cohort, average age within the cohort, and it wouldn't surprise me if it's distributed very unevenly across the population.
Using my cohort as an example: A brother-in-law took 18 months to feel normal again. One of my neighbors reported that three of her friends took at least 3-6 months before they felt better. She herself got it and said it took "months" to feel better. Yet my boss said I'm the first person he knows who has LC.
One thing's for sure: Covid seems like a pretty bizarre disease. :-)
A sizable chunk of the work force has dropped out due to long COVID. You don't see them, because they don't show up at work or go out much. They're just not there.
Bloomberg: [1]
Brookings Institution: [2]
Northern Trust: [3]
JAMA: [4]
NIH: [5]
[1] https://www.bloomberg.com/opinion/articles/2022-12-07/long-c...
[2] https://www.weforum.org/agenda/2022/08/long-covid-work-econo...
[3] https://www.northerntrust.com/japan/insights-research/2023/w...
[4] https://jamanetwork.com/journals/jama/fullarticle/2801719
Just google 'post viral fatigue syndrome.'
Acute onset ME/CFS is also frequently linked to a viral infection.
I think there is a lot of overlap with burnout too.
Basically when you are in a chronic state of stress from work or other factors, a viral infection can be the straw which breaks the camel's back, which can provoke a burnout.
Repeat every month as new variants start to spread.
Consider it a 'nationwide immune system'.
Would there be ethics problems - surely yes. But if it can be shown to save lives, can we ethically not do this?
Ex: https://www.politico.com/news/2023/06/04/how-covid-made-it-n...
The vaccines dangers are questionable. There are huge incentives to cover up any dangers and pharmaceutical companies and governments have a long history of covering up dangerous medial products and drugs.
There is nothing that isn't a fact about what I just said. I'm not downplaying anything. You are, in fact, overplaying the risks of covid. Which itself is a form of misinformation that somehow has been allowed to continue to circulate.
What danger got "pushed by the media"? Are you talking about right-wing media that downplayed the dangers all along ("it's just a flu!")?
> The median age of death from covid is higher than the average life expectancy of a human. Most healthy people under the age of like 70 will handle covid just fine. This is an absolute fact that downplays nothing.
Sure. Most healthy people will still benefit from the vaccines, as they lower the chance for long Covid for the ~10-15% of healthy people who don't handle Covid just fine, and it - you know - keeps those not healthy and under 70 from dying. Small things like that.
> There is nothing that isn't a fact about what I just said. I'm not downplaying anything. You are, in fact, overplaying the risks of covid.
Where have I done that? You just went off and said "it's not that dangerous" without even stating what you're comparing the level of danger to. You were, literally in the most literal sense, downplaying the dangers of Covid while talking up the dangers of the vaccine.
Trust me. I was you before these lockdowns. I even phone banked for Obama. I had nightmares when trump was elected. I sneered and disowned trump people. Now I’m a political orphan who will probably never again vote (D).
My (former) political party tossed literally their entire platform to hitch onto covid hysteria.
Stop playing tribalism. It isn’t healthy and sets you up to get played. We are all just people. Most of us are right in the center just trying to live. Both parties are authoritarian, fascist assholes that want to steal your rights.
Covid was and is real but it turned political and not in the way you think. You and a lot of other people like me got badly, badly played. Once you realize that, all the mental gymnastics required to support your takes on covid melt away. And even better, you can finally stop hating other people. Unfortunately it also means you’ll have to accept you probably wasted three years of your very short life playing covid theater and getting all worked up about other people (rightfully) disregarding all of it…
My guy, I'm not even from America, and I don't cleanly fit into your political system. It's pretty rich of you to say "I was you" when I haven't stated my own position so far. Yes, I know, you want to project your own journey onto me to make it seem like you're more evolved than me - that's what enlightened centrists who just so happen to veer right always say. But if you jump the gun and start this before I clearly state my own position it will just make you look like... well, like you do now.
> My (former) political party tossed literally their entire platform to hitch onto covid hysteria.
Really? The Democrats left their entire platform behind? If I were to compare Bidens platform today with Obamas from 2012 there would be no overlap? Nothing about healthcare, or social services, or taxes etc?
> Stop playing tribalism. It isn’t healthy and sets you up to get played. We are all just people. Most of us are right in the center just trying to live. Both parties are authoritarian, fascist assholes that want to steal your rights.
I'm an outsider looking into the clusterfuck you guys call politics. I'm stating my subjective views as such. What you call tribalism I call "human decency" - calling out people who downplay the dangers of a virus for example is something we should all do for those who can't anymore, because they died.
> Covid was and is real but it turned political and not in the way you think. You and a lot of other people like me got badly, badly played. Once you realize that, all the mental gymnastics required to support your takes on covid melt away. And even better, you can finally stop hating other people. Unfortunately it also means you’ll have to accept you probably wasted three years of your very short life playing covid theater and getting all worked up about other people (rightfully) disregarding all of it…
The funny thing is that you haven't stated any single specific thing that got changed, or that I should change my mind on, or that signifies your move to "the center" (as you call it). It's all just platiudes and big nebulous terms ("my former political party tossed literally their entire platform", "you and a lot of other people like me got badly, badly played", "all the mental gymnastics required to support your takes on covid melt away"). Is it possible for your to say anything of value?
It's not hard to see that each of these factions have taken views (quite stridently in fact) that would have been anathema to their positions not all that long ago. Views can evolve, but we're talking about total reversals in a very short period of time.
This is fine with me, but what's been very eye-opening is listening to the same people who were stridently in favor of view X just a few years ago are now stridently in favor of Not-X, and not only that, they think you're a monster for thinking X.
It's not R vs D, it's tribalism, as you said. I just didn't realize how strong it is and how close-minded it makes people to alternate views. Belonging is clearly an incredibly strong thing in humans, the need for it seemingly making suspension of disbelief involuntary. I'm aware I'm probably _still_ stupidly believing things for no reason than some group I like thinks it, so this isn't me being superior. It's just something we as humans should be wary of.
COVID risk seems to be mostly related to other, known risk factors that are personalized.
This is supported by most current medical literature.
What matters is how people evaluated the information at the time when there was uncertainty about the severity.
Just because he the poster may have gotten lucky doesn't mean his arguments were well founded during the time period where it mattered.
Let's cut to the heart of it, this 'not in my body' argument is just a rationalisation for an oppositional personality trait.
Hey, I hate being told what to do, but I don't push it to the point where I refuse to do something which benefits me.
No personal choice about the air pollution every american breathes.
Seems odd to offer personal choice about things which are likely more beneficial.
His only recourse after doctors were clueless was a naturopath. Now high dose of vitamins and never ever stopping is the only way he can stay moving. I'm talking like 100hr weeks doing beekeeping moving beehives around the country, dragging tonnes of beehives using 4wd and trailers, winching up 4wd tracks etc and in the off season wheeling and dealing vehicles.
If he takes a holiday his immune takes a dive and he gets sick as a dog.
On one hand you'll know and be able to blame your genetics while working with your healthcare providers on any developing treatments. On the other hand, that data could potentially be used against you in the future for life insurance, disability insurance, or long term care insurance.
Seems like a damned if you do, damned if you don't type of situation. Make sure you read the privacy policies of any provider you go through. DNA is the most personal, private, and detailed part of you. Is it really worth it?
Depends on the meaning of “they”.
(I wonder if there any recorded instances of people swallowing microSD cards from their dashcams after car crashes...)
https://en.wikipedia.org/wiki/Genetic_Information_Nondiscrim...
Genomics has a terrible hype problem, like ML. Genomics researchers have decades of experience making their papers souond far more significant and actionable than they really are.
We've mostly moved past the "we found a gene for..." which sort of considers phenotypes as mendelian (only two alleles per gene, independent segregation, single SNP is highly penetrant, etc) to the association approach, which as you point out, isn't satisfying from a causality or mechanistic viewpoint.
In adopting the association approach we have learned (unsurprisingly IMHO) that most organismal phenotypes (I'm treating this risk as a phenotype, which is a fairly loose interpretation) are caused by the interaction of the environment and thousands of changes to thousands of genes, all of which are non-additive and non-linear.
Such as specific mutations of MTHFR or BRCA. These are essential screens for people to know.
1) one or several mutations in the protein FOXP4 affects susceptibility to long covid [edit: reading the paper more after my coffee, the affected region isn’t actually in the coding region of FOXP4. “ no variant in LD with the lead variant is coding”]
2) a variant in a region that controls expression of FOXP4 affects long covid.
3) variant(s) in a gene near FOXP4 is actually what’s causing long covid (though this is somewhat less likely given the locations of the snps that are associated).
To make this more complicated, genes starting with FOX are usually transcription factors, meaning they control the expression of many other genes. So it’s certainly plausible that it’s a hinge point that controls a large, amorphous downstream response. I don’t know much about the biology of this gene in particular.
What one could say with moderate confidence after a 23andMe style test (assuming they have one or more associated variants) is that you might be at elevated risk for long covid, but only about twice the likelihood as the general population, assuming I’m reading the figures right. Not insignificant risk, but not perfectly predictive either. Where this result is more useful is directing further studies on the mechanism of long covid and (once we understand that) potentially ways to treat the underlying cause.
In short, genes like this have their hands in so many pies you can't just patch it and not have side effects.
For example slow COMT people are more likely to be depressed or have some other mental symptoms. And that's because the COMT gene is responsible for producing an enzyme actually breaks down specific hormones so that some thoughts don't linger.
We need to do that work next - what is the probable mechanism - before we should say - this gene causes this.
https://www.ecfr.gov/current/title-42/chapter-IV/subchapter-...
(Edit: per tssva—LTD & life are generally state laws, GINA is health ins and employment)
Or rather, US does not have health care.
It’s almost deterministic at this point, and you see how they did it for clawing back reproductive rights.
And this issue is obscure enough for a small enough current population, that you would not be able to actually build a robust counter protest in any kind of sensible way.
So really all it would take is a handful of just Millionaires to care about this problem to throw — let’s call it $10 million - at lobbying in order to make it go their direction.
And fully agree on the DP.
I caught several downvotes and you can't downvote replies, so I was talking to the audience on the second comment.
The 1st state I checked to validate that, my own, doesn't. The state level laws much like the GINA act only cover employment and health insurance. There is a newly enacted law preventing consumer genetic testing companies from disclosing results without consumer consent, but nothing stopping an insurance company requiring consent for access or requiring their own genetic testing before issuing life or disability insurance. Based upon this I'm not comforted by the assertion that "pretty much every state has a law".
Even if you didn’t consent, genetic genealogy can still be used to triangulate your genome from relatives of yours who do consent. This is still a manual process for now, but it’s very likely that a CODIS-like system to automate DNA triangulation for purposes of fingerprint search will be implemented soon. Only a small step from there to insurance companies being able to deny you coverage based on an “sub-clinical family history” of something.
The term "sub-clinical" means "something that has not yet caused you any problems bad enough that you mention them to a doctor, and therefore never makes it into your medical history; and which also would not yet be revealed by a medical examination."
To be clear, a "sub-clinical family history", then, isn't information about your sub-clinical conditions attained from medical data about your family's clinical interactions (that would be a regular family history!); rather, it's information about your clinical or sub-clinical conditions, deduced through triangulation of your (potentially quite distant!) relatives' sub-clinical conditions, which were in turn discovered through genetic screening of those distant relatives, that they themselves did consent to, as some presumed-boilerplate when submitting their DNA to ancestry websites and the like.
There is currently no way for insurance companies to be aware of your "sub-clinical family history" besides just asking you. With automated triangulated genetic screening, they would have a way to get around asking you.
https://havenlife.com/blog/family-medical-history-life-insur...
They also take into account smoking. Playing devil's advocate if a car insurance company can charge you a higher premium because you are male why shouldn't a life insurance company use your genetic code?
I can't trust such people to put in place and operate any system that truly protects medical privacy.
After the very recent forced masking and "vaccine passports" debacles (which inherently forced the public disclosure of what should be private medical information), and the related coercion and forcing of unwanted medical procedures that such "professionals" advocated for and participated in, it should be clear that they don't take medical privacy seriously.
Oh, you're one of those
My genome is publically available and from what I can tell there is no extra cost to me over the past 10+ years that it's been around.
In the past we have carried out studies with partners where we shared individual level data and obtained consent to do so. We recruited people with certain diseases to participate in those studies. The data was always de-identified and for research use only.
https://www.gsk.com/en-gb/media/press-releases/gsk-and-23and...
Details (and reading comprehension) matter
https://jamanetwork.com/journals/jamainternalmedicine/fullar...
The gene could be encoding for neuroticism, or general respiratory problems, for all we know.
"A serology test result positive for SARS-COV-2 was positively associated only with persistent anosmia (odds ratio, 2.59; 95% CI, 1.57-4.28), even when restricting the analyses to participants who attributed their symptoms to COVID-19 infection"
The study conclusion says so:
"Although our study cannot determine the direction of the association between belief and symptoms, our results suggest that further research regarding persistent physical symptoms after COVID-19 infection should also consider mechanisms that may not be specific to the SARS-CoV-2 virus. From a clinical perspective, patients in this situation should be offered a medical evaluation to prevent their symptoms being erroneously attributed to COVID-19 infection and to identify cognitive and behavioral mechanisms that may be targeted to relieve the symptoms.23"