Covid-19 is 10 times deadlier for people with Down syndrome
sciencemag.org
sciencemag.org
So it seems to be less about something special about Down's syndrome that makes COVID more deadly to someone with Down's, but that it is just a subset of people who tend to have increased severity of respiratory infections in general. And COVID, being a somewhat respiratory virus, naturally hits those people harder than those without extra susceptibility to respiratory viruses.
As a parent I would be absolutely devastated if my child had Downs and was killed(#) because of the poor behaviours at display in society.
(# Speaking as someone living in Australia where appropriate measures were eventually taken to protect everyone; my son has a different disability which impacts him, and us, greatly, so perhaps I empathize stronger for that reason. My opinion is that not taking easy preemptive measures to stop the spread is akin to reckless endangerment with completely needless death being the outcome. Thus "killed".).
What would be vastly more interesting is if someone, somewhere with some medical expertise was wondering why people with Down's Syndrome are, in fact, dying at high rates while people with Cystic Fibrosis -- another genetic disorder and infamous for killing people at young ages via respiratory infection -- are not:
Does cystic fibrosis constitute an advantage in COVID-19 infection?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537774/
Edit: And I say it would be vastly more interesting because of the potential to cast light on the pathology of the disease and thereby cast light on how to treat it effectively.
Someone with Downs isn't necessarily as able to make accurate risk calculations and may find themselves engaging in riskier behavior.
Add to that the fact that many adults with Downs may live in community group homes alongside others with mental health concerns (staff coming in and out - vector of infection), whereas those with CF may be less likely to do so, as (unfortunately in a human sense, fortunately in the sense of comparing with prior decades and the progress of treatment) their average life expectancy in the United States is under 40 y/o and they may be able to isolate with retired adult parents or work from home.
It felt like having bad anemia. The impact it has on the blood was a big deal but it did not seem to hit my respiratory system hard. If anything, it appeared to have some beneficial side effects for some longstanding issues.
So I think your quick and dirty dismissal of an important biological difference is specious.
It might be interesting to get an antibody test to confirm that it actually was SARS-CoV-2?
Which organ system is primarily affected by your CFTR mutation? I quickly checked the lit and I gather Atypical CF can mainly affect respiratory, gastrointestinal, endocrine and metabolic, or genitourinary systems and is a little different in this way than classic CF, but you probably know more about it than I do.
Do you guys have a pretty rough history of respiratory infections, or do you see it manifest primarily elsewhere? Are you guys on prophylactic antibiotics for chronic pulmonary infection?
What were the beneficial side effects?
Curious to hear your hypothesis as to how CFTR mutations could lend an advantage to patients with COVID? I haven't got any ideas.
Were you guys much, much more cautious with isolation? Do you work in the community, or were you very cautious about isolation?
Super curious to learn more.
Edit: I looked at the paper and behavior was cited as a possible key factor. "...typical behavior in patients with CF, who might wear protective masks and avoid contact with sick people..." Another idea they floated was disruption of IL-6 signaling, which they didn't figure would totally mask (ba dum tss) the respiratory effects of the virus, but might knock it down a bit. Iono, small sample size too.
There doesn't seem to be much data as to whether or not CF folks have any actual biological protections or if they're not just being more cautious, but I found a couple of papers that hypothesize potential mechanisms:
Peckham, D., McDermott, M.F., Savic, S. et al. COVID-19 meets Cystic Fibrosis: for better or worse?. Genes Immun 21, 260–262 (2020). https://doi.org/10.1038/s41435-020-0103-y
https://www.nature.com/articles/s41435-020-0103-y
SARS-CoV-2 (COVID-19) and cystic fibrosis. Bruce A. Stanton, Thomas H. Hampton, and Alix Ashare. American Journal of Physiology-Lung Cellular and Molecular Physiology 2020 319:3, L408-L415
https://journals.physiology.org/doi/full/10.1152/ajplung.002...
Hope you find them interesting.
Edit Edit: Based on your screen name, and our previous butting-heads over bullying vs. character building on another thread, I'm reminded of the classic Gary Larson/Far Side cartoon with Ed's Dingo Farm adjacent to Doreen's Nursery, and the caption 'Trouble Brewing.' An absolute classic. I'm perfectly willing to embrace the character archetype of Ed in this hypothetical cartoon situation, although I have yet to be graced with ownership of a dingo farm.
I'm not really interested in answering a whole lot of invasive personal questions. That has a history of going bad places on the internet and just not going there seems to be the only cure for that issue.
Cystic Fibrosis is much more common in Caucasians than in other ethnicities and there are papers out there that posit that this may be because it may protect against cholera and/or tuberculosis, two diseases that ravaged Europe for some time. So it's possible that the mutation became much more common in White Europeans because of it playing a protective role against those diseases.
Tuberculosis is basically a lung disease while cholera is basically an intestinal infection.
The mechanism behind CF is fairly well understood in that we know it boils down to a miscoded CFTR, which is a channel that handles trafficking of certain molecules into and out of the cell. This impacts all cells in the human body, but especially epithelial tissues and especially impacts the mucosa.
Both lungs and gut tissues are epithelial tissues and both are lined with mucus, so CF leads to serious gut and respiratory problems (among other things). The lung issues get the most press, but about 90 percent or 95 percent of people with CF are seriously underweight due to gut issues interfering with their ability to get adequate nourishment.
So people with CF react differently to most lung and gut infections than the average person and in most cases this is very much to their detriment, but not always. There is some evidence that there are cases where the difference serves as a protective factor and that fact is likely why the mutation is more common in some populations than others.
It would be really, really interesting and potentially valuable if someone took that seriously for wondering exactly how Covid-19 works and why it kills some people while others are asymptomatic while infected.
Ok, so from what I understand, much of the fallout from a coronavirus infection in severe cases is resulting from an overreaction by the immune system. What I saw in the original paper you shared is that the most plausible mechanism would be increased propensity for isolation and mask wearing, but the IL-6 knockdown would be through CF deactivating elements of the immune system (immune signaling molecules).
The Nature paper suggests upregulation of inflammation, which seems implausible to me: "Activation of furin, which is increased in CF, together with the cellular damage induced by viroporins, might be expected to upregulate NLRP3 and cause inflammation"
The proposed mechanism in the Physio paper is as follows: "Our analysis revealed that ACE2 mRNA is elevated and TMPRSS2 mRNA is decreased in CF airway epithelial cells compared with non-CF cells. Increased ACE2 is predicted to enhance SARS-CoV-2 binding to epithelial cells but would increase conversion of ANG II, which is proinflammatory, to angiotensin-1–7, which is anti-inflammatory. Thus, increased ACE2 would reduce inflammation and lung damage due to SARS-CoV-2. Moreover, decreased TMPRSS2 would reduce SARS-CoV-2 entry into airway epithelial cells"
So, again, there isn't hard evidence that this is happening at all, but here are a couple of proposed mechanisms that could potentially explain it if it is happening.
Also I skimmed these things, so grain of salt.
Does every article of interest have to be some grand revelation? Science is all about incremental gains, with very rare leaps.
Part of the why was very interesting here imo:
> But genetics may also make them particularly susceptible to SARS-CoV-2, the pandemic coronavirus. They have three copies of a gene on chromosome 21, TMPRSS2, which codes for an enzyme that the virus hijacks to help it enter human cells. The TMPRSS2 enzyme cleaves the spike protein that studs the virus’ surface, launching a series of steps that allows the virus to invade the host cell.
> Cells from people with DS typically express 1.6 times more TMPRSS2 than those from people without the condition
This highlights why those with down syndrome are even more susceptible than those vulnerable groups you mentioned.
How can that be if there is a net new virus and emergency?
> But genetics may also make them particularly susceptible to SARS-CoV-2, the pandemic coronavirus. They have three copies of a gene on chromosome 21, TMPRSS2, which codes for an enzyme that the virus hijacks to help it enter human cells. The TMPRSS2 enzyme cleaves the spike protein that studs the virus’ surface, launching a series of steps that allows the virus to invade the host cell.
> Cells from people with DS typically express 1.6 times more TMPRSS2 than those from people without the condition
But I understood the questioner to be asking about respiratory infections in general (including flu) since the linked article already addresses COVID susceptibility.
> But genetics may also make them particularly susceptible to SARS-CoV-2, the pandemic coronavirus. They have three copies of a gene on chromosome 21, TMPRSS2, which codes for an enzyme that the virus hijacks to help it enter human cells. The TMPRSS2 enzyme cleaves the spike protein that studs the virus’ surface, launching a series of steps that allows the virus to invade the host cell.
> Cells from people with DS typically express 1.6 times more TMPRSS2 than those from people without the condition
It's been really nice to see the civil discourse in this thread, with people taking their respective positions and no one being a jerk. Thank you!
If you or someone you know has just received a diagnosis of a child with Down syndrome, prenatal or not, please help them find one of the several awesome support organizations out there. When we got our diagnosis, it was devastating and scary. The truth is, there's a huge spectrum of outcomes on a large number of dimensions. Heart trouble != intellectual delays != physical delays, etc. So far, raising my typically-developing daughter has been just as hard, just as much work, and just as unknown in a lot of ways as raising my son with Ds.
My wish and hope for the world is that every prospective parent makes decisions informed by facts and not fear. Folks who still choose not to continue a pregnancy (or choose to otherwise give up the baby) will receive absolutely no judgement from me and many people like me. But there's a lot of misinformation and misinterpretation available to you during one of the most emotional and confusing times you may ever encounter.
One such organization is the DSDN [1], which I'm familiar with because my spouse is currently a volunteer with them. There are others including national and local advocacy groups, Gigi's Playhouse, and more. Just please, talk to some new (and long-time) parents who've been there.
The doco was in released in April.
Why is there "raising calls for early vaccination" in December? This should have been decided months ago.
I'm not sure "10 times deadlier" makes sense either. For young people it's ~0. So 10 times 0 is still zero. But people with Down syndrome often work with others with Down syndrome so I think it's obvious what to do.