4 ms·

I did look up specious before hitting the "publish" button and the internet assured me it simply meant superficially plausible but actually wrong and didn't imp

I did look up specious before hitting the "publish" button and the internet assured me it simply meant superficially plausible but actually wrong and didn't imply anything about you as a person. 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.

phobosanomaly 6y ago
It's too late, I'm deeply, deeply offended. And I simply don't understand your reticence to share private health information with strangers on the internet. /s 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.
- DoreenMichele 6y ago
  I'm not qualified to continue this discussion. I have no idea what in heck furins are. I'm just a former homemaker with the rude habit of failing to keel over dead from my condition. I don't speak medicalese.

phobosanomaly 6y ago

It's too late, I'm deeply, deeply offended. And I simply don't understand your reticence to share private health information with strangers on the internet. /s 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.

DoreenMichele 6y ago
I'm not qualified to continue this discussion. I have no idea what in heck furins are. I'm just a former homemaker with the rude habit of failing to keel over dead from my condition. I don't speak medicalese.