That's good. But the lower lungs already get seepage of body serum/humoral igM and igG. If you really want to protect against infections then you have to induce mucosal immunity (and get tissue resident B and T cells) in the surface layer of the upper respiratory. Unfortunately intramuscular vaccinations do not do that, they only give serum/humoral immunity. So they're only the first step to protect against serious disease.
India has just released it's intranasal sars-cov-2 vaccine for use as of a month ago (https://www.bbc.com/news/world-asia-india-64421961). I'm waiting anxiously on those large scale public results. Especially as a booster after intramuscular.
I'm surprised we haven't gotten an intranasal vaccine before now. We've been talking about the issues with intramuscular vaccines in regards to mucosal immunity since the very beginning.
I believe that the technocratic culture of US medicine is standing in the way of research on intranasal vaccines.
What you consistently hear from medical professionals is, "we have this proven technology, it works, the objections to it are irrational, can we please just be sensible?" So far, so good… (I'm a bit of a technocrat myself)
But why are people so afraid of vaccines in particular? There are all sorts of arguments about autism and turning frogs gay or whatever, but people are still happy to take whatever pills the doctor prescribes and hormone-enriched fast food… what makes vaccines different? It seems pretty clear that people are just afraid of needles, and from an evolutionary biology perspective, that's not irrational at all!
But "maybe we should make vaccines that won't scare people" just won't get you anywhere in the US medical establishment. Frightened patients aren't Serious Medicine.
People are scared of needles is incredibly dismissive and likely intentionally insulting. People aren't afraid of the needles; they're concerned about the unknown impacts of what's being injected through the needles. While needle phobia exists, it's very small percentage of those who didn't want the mystery chemical cocktail pushed by those who openly told countless "noble" lies. The vast majority of these people have had hundreds of shots over the course of their lives, including many previously well tested and well understood vaccines (none of which required 1984 style rewriting of the dictionary).
Can't believe anyone is still pushing what's basically a shame tactic that is typically aimed at pre-adolescents. Do you feel smart or virtuous having posted that dismissive and insulting reductive view of people who don't blindly follow "THE SCIENCE" like you do? It's not the needles! It's the contents! How is that not incredibly obvious?
None of this address his main point of 'why the vaccines when pharma has does the same thing a bunch of times to other things yet people still take tylenol (which is demonstrably toxic and causes serious illness and death all the time)'?
The same people who refuse the vaccine take unknown substances in 'supplements' which have no regulation at all. It makes no sense. Explain it.
I refused the vaccine and I don't take supplements unless my doctor tells me to. I don't take tylenol either, or really anything else that I don't absolutely need (e.g. antibiotics for an infection that won't clear on its own).
Maybe these "same people" that you're describing exist, but they definitely aren't everyone in the set of people who refused the vaccine. They might just be the loud people.
Again, I am not asking for specific explanations. The grandparent comment gave a theory as to why vaccines in general have become fodder for public outrage, when those same arguments against them work for other things that are common, with the outlier being 'needles'.
The parent comment said 'it's not needles, don't insult me! it is because this specific vaccine is [same argument against other things which aren't outrage fodder and not addressing any of the other established vaccines which are subject to outrage]. '
It did nothing to explain away the needle aspect except 'needle phobia is uncommon', which explains nothing since a phobia is DSM classified as a 'disorder' and an 'aversion to needles' wouldn't count.
Thanks for telling me about yourself, though. It was interesting.
I can explain it. Tylenol has been around since 1955 and is only demonstrably toxic in overdoses. The mrna based vaccines have been only used for the past couple years, hence long term side effects are unknown.
Not everyone who refuses the vaccine takes supplements. Your comparison is like saying "why don't you take this research chemical ('molly'), you smoke cannabis already".
You said "The same people who refuse the vaccine take unknown substances in 'supplements' which have no regulation at all. It makes no sense. Explain it." I replied to that point directly.
The "outrage over vaccines and not other things" is in part because the mrna vaccines are new technology. People are hesitant to try something totally new on themselves.
>> "The same people who refuse the vaccine take unknown substances in 'supplements' which have no regulation at all. It makes no sense. Explain it."
>> The "outrage over vaccines and not other things" is in part because the mrna vaccines are new technology. People are hesitant to try something totally new on themselves.
> The MMR vaccines are not mRNA. You are completely missing the point.
Ironic, as you now choose to ignore the explanation.
If you failed to explain an implicit assumption, that's ok, as it's hard to communicate over forums. Introducing MMR (there is no reference to this in "another post") as if there was a misunderstanding on the poster's part is a non-sequitor at best and dishonest at worst.
> You missing the entire context of the conversation
The entire comment section of this article can be perused in a few minutes. Cntrl-f and I find all your comments. At this moment there are 5 (4 of which are this thread). There hasn't been some elaborate discussion that's hard to follow.
> replying to a specific part of my response to another person is not a miscommunication,
Apparently you have used my comments to 'prove' that I am dishonest for 'introducing' the fact that pluralization means 'more than one'.
Let's break this down with an example:
P1: What don't you like about milks?
P2: I don't like cows.
P1: Goats are not cows.
Is P1 dishonest? If you say yes, I would disagree with you and say that you are attributing to dishonesty what is for you reading comprehension problem. If you say no then I say you are grasping at straws in order to find flaws in my argument because you cannot find a real one.
Those people maybe not being specialist cannot differentiate those remedies which are "safe" as the poster writes (which equals to "no risks or some risk of mild impact") and those which can have catastrophic impact in the relatively small set of the unlucky.
I think it was perfectly reasonable to take the tact of waiting to see the safety of mRNA vaccines.
Now, however, they’re considerably less mysterious than you say they are. Several billion people have now received them, and any honest reading of the evidence from that would strongly support them being very very safe. If there were serious safety problems, we would have seen them undeniably by now.
There have been many attempts. And many of them have proven successful at the ~42 person trial level that failed in this particular study with a common adenovirus as the DNA delivery agent. The one I linked did work in large scale clinical trials which is why it is now being given to the public.
Plus intranasal influenza a vaccines have been around since the 1960s. I alternate getting intramuscular and intranasal influenza vaccines for best protection of myself and others.
I'm very hopeful for this full scale intranasal roll out of a proven intranasal vaccine for sars-cov-2. I am seriously considering a trip to India to get it as a booster to my 4x mRNA intramusculars from Moderna and BioNTech(Pfizer). I just wish they'd use nebulizers instead of a simple spray. Simple sprays work for the fluid dynamics scales involved in small animal models but as large humans we need nebulizers to get the most complete upper respiratory protection.
In short, we have to consider that other viruses like OC43 and HKU1 either do not have durable mucosal responses, or the response of the immune system is to slow for the viral dynamics of some viruses.
To me the more interesting aspect of this research is the possibility to test susceptibility to severe infection. If you know ahead of time you are high risk, then the treatment and behavior is different than someone who knows they are low risk. Right now we treat everything the same - recommend everyone is vaccinated and everyone wear masks during outbreaks. I’d really like to know how at risk I am, and act accordingly.
(Disclaimer: covid averse, lost family member, upset with society for “being done.”)
I’m not sure what to think about this.
A year+ ago, I would have worried that folks would treat a low-risk evaluation as a permission slip to say “the pandemic is over for me,” stop masking/etc, and thus increase the aggregate spread of the virus to folks who are high risk.
But now everyone is already doing that anyway. So yeah, it would be nice to know whether we are high risk or should just let it all go and say whatever.
Sometimes I think I'm the only low risk person left on the planet wearing a mask and vaccinating. Then I see old folks or one 30y/o woman in the supermarket wearing a mask, and I remember that this protects them too. There's even some performers asking fans to mask up so high risk people can come to their shows. Gives me a tiny glimmer of hope for humanity.
I just read this January 2023 article by a person with last name Fauci that claims coronaviruses have never been controlled by vaccines. More communication problems or admission of mistakes?
Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses
David M. Morens, Jeffery K. Taubenberger, and Anthony S. Fauci
'Because these viruses generally do not elicit complete and durable protective immunity by themselves, they have not to date been effectively controlled by licensed or experimental vaccines. In this review, we examine challenges that have impeded development of effective mucosal respiratory vaccines ...'
> with last name Fauci that claims coronaviruses have never been controlled by vaccines
Actually, the full text is:
"Viruses that replicate in the human respiratory mucosa without infecting systemically, including influenza A, SARS-CoV-2, endemic coronaviruses, RSV, and many other “common cold” viruses, cause significant mortality and morbidity and are important public health concerns. Because these viruses generally do not elicit complete and durable protective immunity by themselves, they have not to date been effectively controlled by licensed or experimental vaccines."
The authors of the paper (not just Fauci) named off a group of different viruses, not just a single one. Taken in the stated context, it should make a lot more sense to anyone who reads this stuff.
Countless studies have shown that SARS-CoV2 can infect systemically and not just the lungs. The SARS-CoV2 virus has been found in virtually every organ and the first autopsy studies in 2020 demonstrated this.
It is horrifying that the person who has lead the response to this virus for the US is a coauthor of this factually incorrect statement 3 years into the pandemic.
Humoral vaccines do provide some limited protection when it comes to transmission. Nothing like a mucosal vaccine would. But an additional line of protection for the susceptible we may come in contact with.
For full disclosure I don't vaccinate anymore (waiting until the mucosal vaccines are available). But I understand those who do, especially if they are around other people when maskless more than I am.
I was under the impression that there is no data showing that the covid mrna vaccines reduce transmission. If you are aware of a source that says otherwise I would love to check it out.
> The ARs among household contacts of index patients who had received a COVID-19 booster dose, of fully vaccinated index patients who completed their COVID-19 primary series within the previous 5 months, and of unvaccinated index patients were 42.7% (47 of 110), 43.6% (17 of 39), and 63.9% (69 of 108), respectively.
I appreciate the response. Hard to draw many conclusions from that study for a number of reasons, but perhaps the greatest in my mind is highlighted near the end: "TCOVID-19 prevention measures (vaccination, isolation, and mask use) are likely highly correlated within households, and the identified risk factors might not be independent predictors of transmission".
Basically this article doesn't show that vaccines prevent transmission. It doesn't show they don't either, although that there wasn't a more dramatic effect is a negative finding in my opinion. I wish the authors had analyzes the AR in vaccinated vs unvaccinated household contacts.
On the other hand, the authors there start their conclusion off with The high risk of bias in the trials, variation in outcome measurement, and relatively low adherence with the interventions during the studies hampers drawing firm conclusions.
But it's a short discussion, people can go read it for themselves.
"The high risk of bias in the trials, variation in outcome measurement, and relatively low adherence with the interventions during the studies hampers drawing firm conclusions."
Means they aren't sure themselves, if their results are usable at all. For the individual, one unmasked exposure undoes the entire effort. We're not talking about toxicity.
This seems to be clear to the authors aswell. The strongest language in their conclusions reads like this:
"There is uncertainty about the effects of face masks. The low to moderate certainty of evidence means our confidence in the effect estimate is limited, and that the true effect may be different from the observed estimate of the effect."
Going from that to "Masks don't work" is quite the leap.
"We included 12 trials (10 cluster‐RCTs) comparing medical/surgical masks versus no masks to prevent the spread of viral respiratory illness (two trials with healthcare workers and 10 in the community). Wearing masks in the community probably makes little or no difference to the outcome of influenza‐like illness (ILI)/COVID‐19 like illness compared to not wearing masks (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.84 to 1.09; 9 trials, 276,917 participants; moderate‐certainty evidence. Wearing masks in the community probably makes little or no difference to the outcome of laboratory‐confirmed influenza/SARS‐CoV‐2 compared to not wearing masks (RR 1.01, 95% CI 0.72 to 1.42; 6 trials, 13,919 participants; moderate‐certainty evidence)."
It always amazes me when someone ignores the 99 studies that show masks are effective, and highlights the one that says maybe they’re not. Cherry picking in action!
Is this meant to be irony? You seem to have not read the link. It's a meta-review of 78 randomised control trials. It is literally the opposite of cherry picking.
You then cherry pick one review saying the opposite.
You're still touching things, then touching your face. You're still breathing the same air as everyone. You're still moving through clouds of expelled vapor from everyone who has walked in front of you recently. There is no hermetic seal around your nose and mouth if you wear a mask. Your eyes are exposed to the air. And if you wear the same mask more than once, you are trapping all sorts of bacteria and other nasties in a soup of sweat, oils, and grime on your face. Masks are mostly theater in everything but controlled environments.
> You're still touching things, then touching your face.
> Your eyes are exposed to the air.
I'm not the person you're responding to. Just what I do.
The mask covers the mucus membranes, except around the eyes. And I've got glasses with side-shields for the eyes. And an ASTM-III mask over the N95 mask so that I can touch and manipulate the masks without touching the breathing surface of the N95.
> You're still breathing the same air as everyone. You're still moving through clouds of expelled vapor from everyone who has walked in front of you recently. There is no hermetic seal around your nose and mouth if you wear a mask.
It's a virucidal N95, so besides the filtering also kills much of the virus that it traps. While the filtering is not 100%, the killing on top of the filtering should greatly reduce risk of infection or transmission in the unlikely event I'm infected but don't know it.
> Masks are mostly theater in everything but controlled environments.
I used to get a respiratory infection about yearly. I haven't had a contagious illness that I am aware of since January 2020.
Edit to add: And I take my daily shower after coming home for the day. I have never used a delivery service to grocery shop. I got about one month of work from home before coming back to the job part-time, and was fully back to the job by September or October of 2020.
I wear an N95 when I go out but only my regular glasses. I too haven't been sick since January 2020. I used to get colds pretty much quarterly, and so it's absolutely worth it to me. If it bothers someone else to see me wearing one that's their problem, I'm not asking them to wear one.
I get the ocassional weird, sometimes mean look every once in a while, but I can deal with that as long as people don't stop and confront me over it, which thankfully hasn't happened yet, except a single time when some jerk walked past me and baa'd to suggest that I was a sheep back in 2020.
I don't even wear a mask everywhere (not since I got vaccinated). I don't once I sit at a table at a restaurant, or at certain social functions. But somehow I still haven't gotten Covid yet (that I'm aware of at least), even after a few known exposures, so I'm guessing either it's helping at least a little bit or I had an asymptomatic case a while back.
As far as I know, though, I could still have a moderate-to-bad case of it when I get it. My parents just both got it recently, for example, (that was one of my exposures, since they were helping me clean out my flooded basement just before they got symptoms) and it took both of them over a month before they got over it, and we share genes, so in theory I should have a somewhat rough time once I get it as well.
I used to get them more than yearly, usually 3x or more per year, some of them were pretty brutal (Really bad coughs, fevers, night sweats, up to a week of PTO to recover)
I have masked every time I leave the house since COVID started impacting Wuhan (we had Chinese operations, so saw early impact on the business side. If you saw me masking on BART in early 2020, wave) and I haven’t gotten a single illness of any type since then.
It’s glorious.
I am often close to the only person I see all day masking, and it blows my mind why people don’t get this advantage.
> if you saw me masking on BART in early 2020, wave
Which line, what time? :) I only started riding BART in late 2019, so only had a few months of it before stopping. I'm sure I would have been ill more often than yearly if my ridership had continued.
I agree. Additionally the masks will more than pay for themselves when it comes time to cash out my accumulated sick leave when I leave this job.
You were about half an hour later than me on the way out, and we only overlapped through Orinda to Rockridge. I usually got the 2:something on the way back, and by then it was crowded enough I'm sure I wouldn't have seen you even if we were in the same car.
If there's a one in a million chance that my wearing a mask might prevent me from unwittingly getting or transmitting COVID and that spreading to a high risk person, I'll take it. You make your life choices, I'll make mine. Thanks.
If you or someone in your family is immuno-suppressed, have at it. Otherwise in terms of risk avoidance you might as well start wearing a crash helmet when you ride the bus just in case.
30,000 die in the US in car accidents every year. crash helmets, race harnesses, and roll cages would save thousands of lives. but I get that some people rather die than wear safety gear.
I understood masks were not about making you proof against infection, but instead for slowing the spread so hospitals could respond. That's the critical measure of mask effectiveness.
Comorbidities have always been indicators of risk. You're more likely high risk if you already have health issues, are morbidly obese, or over the age of 70.
When people complain about prejudice against fat people, this is what they mean.
I fail to understand why someone's size would make their advice less credible, particularly on topics other than weight loss. If anything, being at higher risk would dispose them to take the virus more seriously.
After all, "trying to eat healthy" is rarely successful. The vast majority of dieters do not succeed in achieving long-term weight loss.
Fat people have often tried a variety of weight loss techniques. Their advice is liable to be more pertinent than a skinny person who has trouble gaining weight.
"Carrying too many pounds is a solid signal of current or future health problems. But not for everyone. Some people who are overweight or obese mange to escape the usual hazards, at least temporarily. This weight subgroup has even earned its own moniker—metabolically healthy obesity."
"But some people who are overweight or obese manage to avoid these changes and, at least metabolically, look like individuals with healthy weights. “Obesity isn’t a homogeneous condition,” says Dr. Frank Hu, professor of nutrition and epidemiology at the Harvard School of Public Health. “It appears that it doesn’t affect everyone in the same ways.”"
So if it works for a person with a lot of bad habits you think it's a bad idea? Wouldn't something that works for a person with a lot of bad habits be even better?
I particularly like the nose spray application. If even non-susceptible people get in the habit of using a nose spray before starting their day, any contagious viruses that they may already have could be covered with an inactivator upon sneezing them out. Hypothetically this could protect susceptible people who inhale the sneezed out viruses.
Very interesting, according to the authors it’s “like velcro”.
> [Covid] primarily uses a protein called the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. Lung cells have high levels of ACE2 receptors, which is why the COVID-19 virus often causes severe problems in this organ of infected people.
> Like ACE2, LRRC15 is a receptor for coronavirus, meaning the virus can bind to it. But unlike ACE2, LRRC15 does not support infection. It can, however, stick to the virus and immobilise it. In the process, it prevents other vulnerable cells from becoming infected.
> “We think it acts a bit like Velcro, molecular Velcro, in that it sticks to the spike of the virus and then pulls it away from the target cell types,” Dr Loo said.
> “Basically, the virus is coated in the other part of the Velcro, and while it's trying to get to the main receptor, it can get caught up in this mesh of LRRC15,” Mr Waller said.
Given then that this protein is synthesized by our body, and in people with less severe COVId more of this protein was found, and less in more severe cases, could mRNA injections be used to stimulate/ramp up production?
The approach mentioned in the article is a nasal spray which I suppose is easier to manufacture.
This then begs the question, could mRNA injections be used in place of traditional medication?
Probably no if the medication needs to be targeted at a specific region, yes?
Could it be that the complexity of the protein affects our capacity to produce medication for it?
Or is it that the means of administration is the main factor on how we select our approach?
With mRNA vaccines we get the cells to produce the protein. Does this imply that synthesis of the spike protein is difficult, or is it that administration is?
> With mRNA vaccines we get the cells to produce the protein. Does this imply that synthesis of the spike protein is difficult, or is it that administration is?
It's that the mechanism of production of spike (inside infected cells) parallels the mechanism of production of spike protein in a natural infection. This stimulates the immune response against spike without need for additional adjuvants.
> This then begs the question, could mRNA injections be used in place of traditional medication?
Not my specialty, but as you say targeting may be difficult. There are various lipid carriers that I believe can target certain cell types or tissues, but I don't know how well these work, and of course actually distributing them so that they will reach lung tissue is also a matter. And then how well would they work in already infected lung tissue versus just spraying the lungs with the protein?
As for the second segment. I only have more questions now. Could it be that requesting that the cells produce additional proteins of a particular kind "overloads" them or simply "asks too much" in a fashion similar to a virus?
That seems unlikely unless the administered medication is simply "too much". I wonder, is there a saturation point? ie a point where additional mRNA medication does not result in more cells producing the target protein? Seems likely.
Which then raises the question, if such a saturation point exists, then what is causing cells to explode due to virus replication? Is it that the viral particles can not escape the cell and thus they "use" pressure? If so, have we encountered a virus that "opens up" a cell without damaging it and eventually becomes parasitic to the host?
It's probably the case that when cells die prematurely, they leave traces for our immune system to trigger an issue, so not destroying the cell seems like a beneficial evolutionary advantage. Otoh, the additional code required for this is likely very "expensive".
I hope a virologist drops by and clarifies on this.
I'm not a virologist, and this is taxing to my memory, so it will be a bit more basic than you might prefer, and won't be as accurate.
> Could it be that requesting that the cells produce additional proteins of a particular kind "overloads" them or simply "asks too much" in a fashion similar to a virus?
It could be. I believe that most of the cells that express from the mRNA vaccine do indeed die (from the immune response against them). I'm not positive about this though. In general if a cell is preferentially producing protein from a particular mRNA it doesn't have to resources left to do what is expected of it (including cellular maintenance).
> then what is causing cells to explode due to virus replication?
https://bio.libretexts.org/Bookshelves/Introductory_and_Gene...
"During release, the newly-created viruses are released from the host cell, either by causing the cell to break apart, waiting for the cell to die, or by budding off through the cell membrane."
According to the video below it can be caused by crowding. I think it can also be caused by virus proteins, or an apoptotic response - programmed cell death done to hinder the viruses ability to replicate more infectious particles. Often enough the cell does not burst, but simply buds off new virus. This is still very detrimental because the cell isn't doing what it is supposed to do, instead having been hijacked to create new viruses.
> If so, have we encountered a virus that "opens up" a cell without damaging it and eventually becomes parasitic to the host?
What I'm going to say won't directly answer your question, but it will answer the question you would have had if you knew a bit more. You want to look up lytic versus lysogenic viral replication. A basic overview: https://www.khanacademy.org/science/high-school-biology/hs-h...
I’ve seen the spikes mentioned a lot. Are these mechanical descriptions of how the spikes operate dumbed down for the average person to understand? Im surprised we don’t hear more about biologically destroying the cells instead.
My background on this comes from a neuroscience course in gradschool. The idea is that molecules and proteins “bind” to receptors which cause a cascade of reactions. The binding depends on the shape of the proteins and receptors.
A bridge like protein is created by removing parts of the spike protein through the cascade. The bridge connects the virus and the cell, and folds into itself to cause the two cells to merge.
I am not sure why it is called spike but I’d guess it’s because it looks like tiny spikes on the virus.
So when what we do with mRNA vaccines is produce the mRNA that encodes this protein, and wrap it in lipids which allow it to enter the cells and the cells manufacture it.
Now, our cells don’t naturally produce the spike protein, so this triggers our immune system to build antibodies which bind onto the proteins and render them useless, or flags for certain parts of our immune system. This results in increased production of certain cells and proteins for this specific protein.
Our immune system has the capacity to create antibodies for and bind onto all sorts of different proteins. This is because it the immune system is allowed to recombine and order its DNA. In order to avoid wrecking havoc at our own body, the immune system passes through filters which filter out proteins that would bind to the naturally occurring proteins in our body.
Van der Waals force[1] is sort of midway between chemical and mechanical interaction. We think of proteins as crystals because that’s how we can image them, but really they’re sort of floppy things that can often change their shape dynamically in response to forces and then exert different forces because of that. This leads to all kinds of interesting feedback loops. The polarity of the water molecules they’re floating around in plays a role too.
> “For me, as an immunologist, the fact that there's this natural immune receptor that we didn't know about, that's lining our lungs and blocks and controls virus, that's crazy interesting.
In February or March of 2020 there were two interesting and not well distributed studies. That of immunity of heavy smokers - and/or those who were heavy smokers but had quit, and the other was about the effects of hibiscus on the mucosal lining of the lungs preventing respiratory infection.
I'm overburdened right now, I can't deal with any more COVID studies. But when I read the title and seeing some comments I wonder if the prior art is related.
It was a wildly popular view here on Hacker New at the height of covid hysteria that even those with natural immunity should still be forced to get whatever injections the governments deemed necessary because "it makes the paperwork easier to track if everyone is required and there is ZERO RISK! ABSOLUTELY ZERO RISK!!!!"
There are still a few holdouts here on naturally acquired immunity being inferior to being given the injections but most of them hinge on a theoretical fraction of a percentage increase in potential protection from having both or upset at the prospect that someone might lie about having had covid previously and use it as an excuse to not get injected. Mostly those who rushed headfirst into mindless authoritarianism are trying to pretend they never participated in the hysteria.
Let's not pretend: it was a wildly popular view since the invention of vaccines, because the central thesis of vaccination is a numbers game; an epidemic or pandemic can be stopped once the immunity of a population reaches a certain threshold.
This was recognized in 1905 with the Jacobson v Massachusetts decision, in the 1950s-1960s with mass polio immunization (resulting in the deaths of hundreds of children to prevent the infection of hundreds of thousands in the US), and today with required MMR vaccines to attend public schools. The view that one should be able to opt out of vaccination programs is the novel one.
> Does the existence of this protein explain asymptomatic infections? I wonder what percentage of the population have it.
Our [unvaccinated] 8 year-old had Covid last Spring and his symptoms lasted exactly one entire morning.
PCR swab tests were done in school on day 1, on day 2 I got a frantic phone call from his school at 7am saying "keep him home, he has Covid!".
We would not otherwise have known, since he had precisely a bit of a headache. No cough, no fever. He took a paracetamol and sat in front of the TV. By the afternoon the headache was gone.
He tested PCR positive again on day 6, so got to enjoy the full 10 days' mandatory isolation, thanks to the rules in place here at that time.
The interesting question is: what percentage of young and/or healthy people actually had a severe case of Covid? We know an awful lot of people who've had mild-to-insignificant cases...
Isolating and denying effective schooling to every kid who comes down with a one-day mild illness for ten days does not seem like a risk-proportionate response to me.
Why not? I don't think skipping one week and a half of school when you're 8 will have any real effect in your life neither in the short or long term future. Meanwhile, if they get in contact with someone with some sort of immunodeficiency along the way it could cause irreparable damage.
You have to look at both sides of the intervention, right?
Like if isolating that kid doesn't prevent any further infections, then it isn't doing any good. If isolating them for 3 days prevents a couple other kids from getting infected, it's less clear.
Using PCR tests to evaluate clearance doesn't make sense though, since they can be positive if there are fragments but no viable virus.
> Using PCR tests to evaluate clearance doesn't make sense though, since they can be positive if there are fragments but no viable virus.
It's a cost and time issue. The cost of filtering snot, inoculating a culture dish of infectable cells with the filtered snot, waiting a couple of days for the cells to show signs of infection (cell swelling or bursting), and then running a PCR test on the cells in the culture dish. With high enough throughput you could probably do this for $50 or there about, and maybe three days, to verify whether they were technically still infected three days ago.
Assuming a 180 day school year (which would actually mean a 10 day period would be closer to 3-4% not 4-5%), that means that half of the year they are not in school anyway. So they have a good chance of catching it outside of school days anyway even if they catch it annually. Besides that, if that's that's a huge and consistent problem, school could just reduce the number of holidays by a week or so. The variance of number of school days throughout the world is already larger than that.
The weekends do count, out of the 10 days they'd be out, up to 4 would be weekend days. So, really they'd have missed around 6 or 7 days of actual school. But it could also happen to fall in a public holiday, which will reduce the number of days even more. And there are school breaks throughout the year.
I find it hard to believe that many people are living such in the edge that, if their kid has to miss a week or so of school in a year their finance and jobs fully crumble.
There's 104 non school days regardless of any other days without school. It only takes 76 other days off (June 15-august 15 + 3 additional weeks off) is youe 180 days off.
People who recovered from C19 many weeks ago and are no longer contagious can still test positive on a PCR test.
Catch C19, recover, get the sniffles in the next 2 months, get PCR tested, require a parent to take off work and the kid to sit out 10 days [possibly more than once] is not a reasonable policy IMO.
Our state-run testing facility always did PCR tests using a throat swab, and since I was the one who drew the short straw and took each of our kids there for mandatory tests, I've observed this being done a couple of dozen times over the last three years.
> People who recovered from C19 many weeks ago and are no longer contagious can still test positive on a PCR test
Which is why the EU issued the "recovery certificate" and put it on the same basis as a negative test, and why our schools didn't test recovered children (to clarify: were mandated not to test recovered children) after they returned to school after having Covid.
Testing positive months after does happen, but is extremely rare, and yes, missing few days of school/work is not that big of a deal considering risks involved.
Oh sure. I think we're interpreting the parent comments differently (i.e., I'm understanding sokoloff's and aflag's comments to be about more general precautionary isolation based on symptomatic illness, not necessarily PCR-confirmed infection like logifail's kid.)
I was not really suggesting kids should be isolated whenever they have any sort of possible symptoms. But if you're diagnosed with some contagious illness, it's probably not a bad idea to try to curb the spread.
> if you're diagnosed with some contagious illness, it's probably not a bad idea to try to curb the spread
This was always true, and we never sent an obviously poorly child to daycare/preschool/school.
I've lost count of the number of times I've picked up one of our kids from daycare/preschool/school before Covid after a phone call along the lines of "your child has spiked a fever/vomited/has had an accident and should probably see a doctor".
Wasn't this typically based on common sense by the parties involved, though?
Sure. If your kid is testing positive for a contagious diseases which killed over 6 million people worldwide and left many with long lasting effects, wouldn't common sense dictate that they should stay at home?
PCR testing, as applied in the current COVID testing protocols, is not an appropriate tool to approximate contagiousness. It reliably tells of prior exposure, that's all.
Probably not. It's likely there are worse diseases out there that we just don't check and keep our normal lives being carriers. But once you know, it's probably better to avoid. I think questioning whether or not doing a pcr test is good use of resources. But I don't think skipping school for a few days is where the problem resides.
> Isolating and denying effective schooling to every kid who comes down with a one-day mild illness for ten days does not seem like a risk-proportionate response to me.
Example had COVID, not a one-day mild illness so it might affect other children worse than the kid. I'd like to know what the negative effect of that really is, my gut feeling is that it's zero. People often make it sound like they end up insufficiently educated and socially isolated which is bs in my opinion.
Unless we are doubting the description of the parent, example had mild illness (the patient's experience of ill health) for less than one day: https://news.ycombinator.com/item?id=34752442
Allowing a single covid-positive kid go to school means contaminating a significant portion of the class's students and students' parents. Ten days out of school sounds fine. Long covid is a thing; being unlikely to die does not mean that illness is unlikely to be life-altering.
> Allowing a single covid-positive kid go to school means contaminating a significant portion of the class's students and students' parents
To a first-order approximation based on data from my three kids and their classes/schools, pretty much all the children in all the kindergarten and school classes got Covid last year. All their teachers got it, too, including the vaccinated ones.
Early last year I recall talking to my (then) 8 year-old about his best friend, who was stuck at home for a fortnight after testing positive Covid [this was before we'd all had it]:
me: "How is he?"
son: "What do you mean?"
me: "Is he OK?"
son: "Why wouldn't he be?"
me: "Is he getting better?"
son: "He's not poorly, he's just positive, Daddy!"
> Something between “almost nothing” and “nobody leaving the house” would be nice.
Based on who tested postive (and indeed negative) when, it appears our 8 year-old gave it to my OH, but not to his 12 year-old brother (with whom he shares a bedroom). When my OH had it, she didn't give it to me, either, and I was testing very frequently back then due to work & travel requirements.
There is a hypothesis that the risk of catching Covid from someone may be related to the relative blood types. Based on the veeery small sample size of our immediate family it's definitely not the case that Covid always spreads quickly round a family group, despite us not having changed anything about our family routine when somone in the house was positive. We didn't send anyone to a separate bedroom, no-one wore a mask at home, and we all sat at the meal table together just as normal.
FWIW My 12 year-old and I had Covid approximately two months later, when he caught it in his school and brought it home.
It's very unlikely. Asymptomatic infections of aerosol spread respiratory diseases are not exclusive to sars-cov-2. Most people get asymptomatically infected with Influenza a every single year and often infect others without even realizing it. The more likely guess is that once you have humoral/serum immunity to protect the body proper you just get the upper respiratory infection (since mucosal tissues are not protected by humoral immunity significantly). And that mucosal only infection is less likely to cause serious disease.
It seems that everyone has it to varying degrees, however it probably doesn’t seem to explain asymptomatic infections unless the virus has the capacity to shed the protein which doesn’t seem to be the case, or that people with asymptomatic infection produce enough of this protein that sars-covid-19 has hard time accumulating and causing the disease, and an asymptomatic patient spreads the virus to people who produce far less of this protein.
According to the authors the protein binds “like velcro” effectively immobilising and preventing infection.
Symptoms would occur if sufficient cells were infected thus the second case sounds plausible to a degree.
I am not a virologist so take everything with a huge grain kf salt.
There do seem to be some alternative views on the role of this protein, LRRC15, in the lungs with respect to Sars-CoV-2. See this other paper (Feb 3 2023):
Just to cover the basics, the virus normally accesses cells by binding to ACE2.
> "The interactions between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and human host factors enable the virus to propagate infections that lead to Coronavirus Disease 2019 (COVID-19). The spike protein is the largest structural component of the virus and mediates interactions essential for infection, including with the primary angiotensin-converting enzyme 2 (ACE2) receptor."
There is a key role played in viral production by furin in ACE2-receptor-binding, which is an 'ubiquitous serine protease' in mammalian cells which plays key roles in processing hormones, growth factors, etc. and which is also exploited by many infectious diseases. This feature of Sars-CoV-2 is of course directly related to the notion that the virus was engineered, because:
> "The presence of a multibasic site (Arg-Arg-Ala-Arg) located at the S1–S2 junction, which is cleaved by furin (Fig. 1), distinguishes SARS-CoV-2 from SARS-CoV and all other known sarbecoviruses whose S protein is not cleaved by furin-like proteases during virus maturation in the infected cell. Cleavage of the S1–S2 boundary is a prerequisite for the cleavage of the S2′ site126, and both cleavage events are essential to initiate the membrane-fusion process."
Accounting for the appearance of this furin cleavage site is a problem for anyone promoting a 'natural origin theory'.
Getting back to this new protein and its potential role, the other paper (first source above) seems to have a different conclusion:
> "Levels of LRRC15 were greatly elevated by inflammatory signals in the lungs of COVID-19 patients. Although infection assays demonstrated that LRRC15 alone is not sufficient to permit viral entry, we present evidence that it can modulate infection of human cells. This unexpected interaction merits further investigation to determine how SARS-CoV-2 exploits host LRRC15 and whether it could account for any of the distinctive features of COVID-19."
Their work seems to imply it might not block infection of cells, but instead enhance infection:
> "In order to examine whether LRRC15 might modulate the efficiency of viral entry into ACE2-expressing cells, we employed the naturally susceptible human lung cell line (CaLu-3) that is commonly used as a model for coronavirus infection [47]. We introduced LRRC15 ectopically to these cells to emulate the expression seen in other human lung cell populations we identified in our expression analysis. Compared to unmodified CaLu-3 cells that lack any detectable LRRC15, the expression of LRRC15 modestly enhanced viral infection"
Science is complicated, and popular media reports on recent science are often of very poor quality.
Those are interesting earlier results about LRRC15. The effect of its expression may be dose dependent, with lower levels of LRRC15 promoting infection (or the negative effects of fibrosis) and higher levels inhibiting infection.
It also shows that what happens in cell culture doesn't necessarily translate to in vivo.
> Accounting for the appearance of this furin cleavage site is a problem for anyone promoting a 'natural origin theory'.
I very much think the lab leak origin is quite possible. Whether an engineered virus, or a natural chimeric virus due to bad lab practices (the Wuhan lab collected a large amount of viruses). That said it's not as if other betacoronaviruses don't have furin cleavage sites: https://www.news-medical.net/news/20230209/Assessing-the-zoo...
"The team analyzed 201 Alpha and Beta CoV strains for furin cleavage sites in their spikes. Cleavage sites in spikes were identified from 44 strains, 17 of which have bats as hosts, while 27 have other mammalian hosts. Domestic animals, including dogs, cats, cattle, horses, and rabbits, were also identified as hosts for potentially transmissible CoVs."
> Science is complicated, and popular media reports on recent science are often of very poor quality.
"The University study is one of three independent papers that reveal this specific protein’s interaction with COVID-19."
As I understand it, that lineage of coronaviruses is quite distinct from the sarbecoronavirus lineage and they don't generally infect the same host species in the same geographical regions:
> "For coronaviruses, furin cleavage sites at the interface of the S1 and S2 domain are not unusual, being found widely in betacoronaviruses in the embeco lineage (which are considered to be of rodent origin) as well as in avian-origin gammacoronaviruses and certain feline and canine alphacoronaviruses (with an unknown origin). Furin cleavage sites are also found in certain bat-origin MERS-like merbecovirises, but not—with the exception of SARS-CoV-2—in the sarbecovirus lineage."
For such a specific motif to arise naturally seems to require a scenario like multiple infection of a host species by several different wild-type coronaviruses.
Then there's this feature:
> "So far, a viable natural origin for the SARS-CoV-2 S1–S2 site through recombination or mutation of a bat-origin virus has proved to be elusive. Of note, the S1–S2 cleavage site of SARS-CoV-2 S does not comprise the pattern found in prototypical furin cleavage sites (it is RRxR and not RxK/RR),8
making its origin enigmatic. One feature of the S1–S2 junction for the SARS-CoV-2 spike from the original outbreak is the presence of a leading proline residue, which might have promoted furin cleavage."
Sarbecoronaviruses are a subset of betacoronaviruses. And I seriously doubt we have a comprehensive sequence database of all sarbecoronaviruses. If furin cleavage sites are present in about 21% of alpha- and betacoronaviruses I would expect they would also be present in a minority of most lineages within these clades. "Furin cleavage sites are also found in certain bat-origin MERS-like merbecovirises"
> For such a specific motif to arise naturally seems to require a scenario like multiple infection of a host species by several different wild-type coronaviruses.
Two would be enough. And we know that happens already (ala XBB, deltacron, etcetera).
> > "So far, a viable natural origin for the SARS-CoV-2 S1–S2 site through recombination or mutation of a bat-origin virus has proved to be elusive. Of note, the S1–S2 cleavage site of SARS-CoV-2 S does not comprise the pattern found in prototypical furin cleavage sites (it is RRxR and not RxK/RR),8 making its origin enigmatic. One feature of the S1–S2 junction for the SARS-CoV-2 spike from the original outbreak is the presence of a leading proline residue, which might have promoted furin cleavage."
This is interesting, indeed. I wonder why an engineered site wouldn't use the prototypical cleavage motif, instead using one that might need (if I'm reading the quote correctly) a leading proline residue in order to promote cleavage?
I suppose if people were inserting furin cleavage sites specifically into the Sars-CoV-2 precursor sequence, then they might generate a series of variants to see which one worked best when it came to results of infectivity tests in human cell lines?
Regarding bat lineages and host viruses, this 2019 paper seems to indicate that the other betacoronavirus lineage with the furin site, the Merbecovirus, has a different bat host range from the Sarbecovirus lineage that gave rise to Sars-CoV-2:
"Compared to Sarbecovirus and Nobecovirus, the bat hosts that harbor viruses from the Merbecovirus sub-genus are more diverse. This is in line with the presence of more CoV species belonging to Merbecovirus."
(I generally trust papers on this evolutionary origin stuff published before the pandemic a bit more than those published after, as there might be less conflicts-of-interest issues).
> I suppose if people were inserting furin cleavage sites specifically into the Sars-CoV-2 precursor sequence, then they might generate a series of variants to see which one worked best when it came to results of infectivity tests in human cell lines?
This makes sense.
I think here's the most relevant quote from that article: "So far, no betaCoVs from the sub-genus Merbecovirus have been detected in bats of suborder Yinpterochiroptera."
While the paper does mention one member of Yangochiroptera (Chaerephon plicatus) that has been discovered infected with sarbecoviruses, it looks like there's little room for infectious overlap of merbecoviruses and sarbecoviruses (which predominantly infect Yinpterochiropterans, at least as detected as of the paper publication).
So if the SARS-CoV-2 progenitor did get its furin cleavage site from a co-infection with a merbecovirus, this would have been a really rare event indeed. At least if the co-infection happened in a bat species, and not in another animal or a human who deals with bats.
The article is correct. Infection is the process of a virus entering a cell. Disease is the virus's cumulative effect on the body due to the infection.
Since the protein (LRRC15) mentioned in the article binds to the virus, making it impossible for the virus to infect the cells, it does indeed block infection.
It's an infection of sars-cov-2 which if left unchecked can cause COVID-19 disease. But unfortunately that proper notation train left the station a few years ago.
Which makes the headline even more confusing. How can you be infected by a disease? The article gets it right, even if the headline doesn't, SARS-CoV-2 infection.
India has just released it's intranasal sars-cov-2 vaccine for use as of a month ago (https://www.bbc.com/news/world-asia-india-64421961). I'm waiting anxiously on those large scale public results. Especially as a booster after intramuscular.