Pfizer is testing a pill that, if successful, could cure Covid-19 | Hacker News Reader

Pfizer is testing a pill that, if successful, could cure Covid-19

montrealgazette.com

831 pointsmvzvm491 comments

> Pfizer is keeping schtum about the detail of the lab tests it has completed but says it has demonstrated “potent in vitro antiviral activity against SARS-CoV-2”, as well as activity against other coronaviruses, raising the prospect of a cure for the common cold as well as future pandemic threats.

I have wondered if the COVID-19 pandemic might lead to some results, like extermination of the common cold, that humans would look back on and say that it was a net benefit. Something along the lines of, "yes, 4 million people died, but in fighting COVID-19 we created highly-effective therapeutics for the flu and common cold. Over the following 10 years, these inventions saved 4 million lives and saved 15 million days of lost work/school".

It's hard to think about these things as we are going through the pandemic, but hopefully there will be some good that comes of it. (Of course, it's also possible that by thinking we've 'cured' the common cold, we will open ourselves up to a once-a-century pandemic, where millions are wiped out by what used to just be a common cold.)

mRNA vaccines is already one of those

Those were already well underway.

IIRC yes but they were relegated to academic study. Something being successful on the market is a huge catalyst for other pharma companies to invest on the tech.

The vaccine community was already well aware of the potential of mRNA vaccines, it just needed a bit more development to mature. The pandemic provided that final push, but without the pandemic that would still have happened, just at a lower pace. They'd still be available and successful on the market in 2025 or so.

mRNA-induced production of protein in animal tissues was demonstrated in vivo in 1989. Yes, I know that's very different from large-scale manufacture of a reliable product. But still.

It just wasn't profitable to put a lot of research into. Vaccines are the most obvious application, and vaccines just aren't profitable most of the time. There are few endemic diseases in wealthy countries, and even fewer where you can sell every person a dose in a few years. For most diseases, the total number of doses sold during the patent period would be relatively small. For example, a potential hepatitis C vaccine would probably look like the hep B vaccine's deployment -- with some ~200 million hep B vaccines given the USA over the last 40 years. Compare to a similar number of COVID-19 vaccines sold in under 12 months.

The underlying technology may well be the cure for many types of cancer and a broad solution to most infectious disease. But again, that likely wouldn't pay off while the patents are in effect. So no point in investing heavily.

Pfizer and Moderna were both sitting on quite a lot of proprietary knowledge, based on the sheer volume of patents filed since early last year. Some basic research, hoping for some breakthrough, but mostly just waiting for an opportune time to develop it into something that would be profitable.

Based on the short time period that mRNA is active, couldn't they propose treatments where you need to be injected with more of it every month?

They'd gain a benefit over pills in that a nurse is required to inject the patient

Protease inhibitors have more of a track record in humans than mRNA, having been used widely as a treatment for HIV. Maybe we're more comfortable with our understanding of any possible long term side effects?

Yeah apparently BioNTech is working on a mRna vaccine for cancer

If so (and I've often wondered the same) then it's quite a statement about how much better we might be able to structure our society to solve collective problems we are totally capable of solving without waiting for a major global disaster.

I'm not sure it's an indictment of our pre-2020 society that we didn't try to cure the common cold sooner. Imagine it costs $20 billion to have a 90% shot at coming up with a cure. You might spend a ton of money and come up with a cure, but it's also possible that you'd spend all that money (which could have been spent on more immediate/important issues) and end up with nothing.

The situation is different when COVID is a catalyst because we are already spending $19 billion (for example) on a COVID cure, and along the way we have learned that if we spend another $1 billion there's a 90% chance we'll cure the common cold.

Having been forced into this situation, it makes sense to go the last mile. That doesn't mean the whole trip would have been clearly worthwhile from the start.

>Imagine it costs $20 billion to have a 90% shot at coming up with a cure. You might spend a ton of money and come up with a cure, but it's also possible that you'd spend all that money (which could have been spent on more immediate/important issues) and end up with nothing.

On the other hand, it is an indictment when that's a concern, when a private company trivially spends comparable amounts for buying things like Instagram and WhatsApp to push more ads, milk more personal details, and poison more minds with BS and waste more personal time...

The 'common cold' is any one of hundreds of different viruses... with many different types of viruses within those hundred+ that are commonly spread.

Covid is a specific class of virus (coronavirus) of which there are relatively few variants.

If it cost $20 Billion to deal with Covid, you'd have to spend at least 100 times that for each and every individual strain of virus that tends to be viewed as one 'common cold.'

Oh, and we've already been trying to cure the 'common cold' for decades. The problem is that there's just too many of 'em.

A lot of stuff magically happens when there is absolutely no other alternative. See – all the companies that weren't bankrupted by employees working from home even though for years executives have said that would be the case.

The problem is really of incentives and risk aversion. When there's a tough decision to make without enough clarity on the outcome, people will always prefer the status quo.

When I'm in charge of some software platform that I know has reliability or security problems that no one is willing to prioritize, I have a foolproof strategy. One, write down the list of biggest problems to solve. Two, wait for an inevitable disaster. Three, when leadership is in a panic I present my list and ask for top priority.

How do the conversations typically go when asked "did you know this could happen"/"did we see this coming" or has no one bothered to ask that question yet during the RCA process?

That's when you show the other hundred lists of solutions to things that could go wrong.

I see.

Maybe I'm overthinking it (this happens sometimes, I'm working on it), but waiting around for a security crisis to happen when a solution is in sight, even when facing difficulty prioritizing the work seems dangerous to one's career.

But I admit not knowing a lot of things most engineers just assume are a given, lately.

It's the difference between working in a push vs a pull shop.

In a push shop (e.g. most non-tech businesses / legacy tech), one is forbidden from working on a thing without management signing off on it and pushing the task to you.

In a pull shop, management communicates priorities (increase reliability) and engineering teams pull tasks to fulfill that.

Believe parent is talking about the former, which is always a cluster&#+@ of technically clueless middle management.

I like that dichotomy. If you or anyone else reading this have any thoughts on it, what are some good questions I ought to be asking during interviews to determine what kind of shop I'm talking to might be?

That's been a real struggle lately, and I want to get better at this to avoid these kinds of push shops you're describing

IMHE, people who work in push shops typically don't realize there's an alternative, which makes identifying them somewhat difficult.

On a side note, I've found push shops tend to be highly correlated with length of position (i.e. "What's the longest someone has ever been on this specific team without transferring or pursuing new opportunities?"). But that's probably more accurately identifying heavily regulated industries, which tend to be push shops do to the Byzantine sign-offs required.

I would say don't ask, "Tell me about a time your team originated an idea, took it to production, and the net impact." Because even push shops have the odd exception that can be rattled off. It's more talking about the typical workflow.

The best I could probably come up with is "Take me through a normal task for your team, from idea origination to prod deployment."

If they start with "We were told to do X", then "By whom? And what did they tell you?" (To the latter, did they specify exactly how or just the end goal?)

You’re not overthinking it. Those of us who wait for catastrophe aren’t silent until it happens. We’re just ready and willing to reiterate what’s wrong when it shows up.

Everything about that situation is dangerous to our careers: saying something, saying nothing, saying a lot, stomping our feet, saying we told them so.

But don’t second guess yourself. You’re expressing exactly the right attitude toward addressing things before they’re an emergency. The people who are using those emergencies to get things done agree, we’re just accustomed to getting shut down unless there’s no other option.

Generally not well.

If you haven’t been shot down by an expendable in the past, the best course of action is to find the most complementary position historically taken by leadership, twist to your objective and then credit them publicly with the vision.

The gap can be reconciled privately later.

"that no one is willing to prioritize"

You missed that part. "Here is the email chain it was discussed in, including the bit where I raised the concern of what could happen" is generally pretty solid CYA.

I actually did not miss that part, but thanks for calling it out regardless. The question was instead borne out of curiosity as to know how the follow up and subsequent discussions fare even with CYA in pocket.

What has your experience been? Have you had success reprioritizing necessary and critical fixes that were previously not in scope postmortem?

Oh yes. There is nothing quite like "it cost us money" to suddenly change leaderships' priorities. I've watched as product priorities went from "keep bolting on features" to suddenly "we should rewrite this problematic monolith" when thigns fell over and money was lost.

See that makes sense, perhaps it make too much sense. My last two jobs I fought the same battles of "I discovered x, we really should do something about it because it can have really bad outcomes" and having the concern depri'd and ultimately blow up in all of our faces.

And in both situations even when said thing exploded in a bloody mess I struggled to get the buy in to give the fix the full attention it needed because "we're losing money not having these features" (I mean no, you're not, but ok)

Hence my incredulity but honest curiosity, being an ops guy who over-prepares and tries to keep his leaders as informed and prepared to make a decision as possible, but still feels like he's often left holding the bag is dang exhausting, you know?

Sounds like that's solved by having the list as an action item.

Yes, we knew about it. Also, here's all these other things we know about that will result in similar catastrophes

That’s a sort of reverse-Disaster-Capitalism.

The Shock Doctrine applied to product management

This was my approach until it failed. The people in a position to decide were so preoccupied by (understandable) emergent secondary effect issues that communicating the underlying issue was basically a waste of time.

The only way I could get to solving the problem was by drawing a line in the sand and refusing to work on symptoms anymore. And the only reason that was effective was because my team was so understaffed that my refusal effectively brought all feature work to a halt.

Even then, “solve the problem” buy in was shaky and constantly dismissed/side-stepped. It took a full end to end proof of concept exploit against a production system, being incredibly careful not to actually cause harm, to get support from the top (which I conjured in less than an hour and regret holding those cards as long as I did, but I was seriously worried about how I could demonstrate the vulnerability without exploiting it harmfully).

It's also a question of return on investment (not necessarily in the monetary sense). Due to the high costs of the pandemic, we've also deployed lots of resources to combat it. But that doesn't imply those resources wouldn't create more value for humanity if they weren't redirected.

Keep in mind that if the pandemic results in extermination of the common cold, in the alternative world without a pandemic we would most likely also achieve it, just slower. It isn't a matter of now or never.

Sure, all you need is a man behind a microphone to make a comment like "First, I believe that this nation should commit itself to achieving the goal, before this decade is out, of ____". Make it a national interest, and have the "people" behind it. However, I don't think you could unite the "people" behind anything anymore. Half will be for it, the other half will be against it just because the other half want it.

The terrifying truth is that we have no idea what the future holds and what the long-term result will be of our actions.

Since the future and the result of our actions is uncertain, society is basically executing a search algorithm. This covid crisis has focussed society on finding a local optimum. Though this focussed search will only get us so far. To find a better _global_ optimum, we need a lot of random, seemingly counterproductive search.

Don't get me wrong, I strongly dislike a lot about the current state of society. But I think it's irrational to think that we can predict what will be useful in a hundred years.

One thing that worries me is if we 'exterminate the common cold' will we then preferentially encourage the evolution of something worse? e.g. if the existing Rhinoviruses are somewhat symbiotic, that is, they cause sickness in the host to spread themselves, but they are an annoyance, not life threatening in most cases.

Now if we have a vaccine for those, do those relatively benign viruses evolve to bypass the vaccine, but in doing so pick up more dangerous mutations in that process?

One worry is that if a vaccine allows for transmission but doesn't generate anything when it comes to effects from the virus, it'll let the virus evolve more dangerous mutations without becoming an issue. This could be potentially dangerous to people who are unvaccinated or if it manages to get past the vaccine. I'm probably pretty in favor of keeping the common cold as it's never killed anyone and helps train the immune system

> One worry is that if a vaccine allows for transmission but doesn't generate anything when it comes to effects from the virus

That isn't a real worry, that is a science-fiction worry.

Viral load, transmissibility and virulence are fairly tightly coupled and they will definitely not come fully uncoupled like that.

At the risk of sounding like someone who is posited against the vaccine (I'm not, and I'm looking to receiving my second dose soon), where is your citation on this?

Data from Israel suggests that the vaccine reduces transmissivity by 70 or so per cent. I do not have the link handy, but there is definitely a coupling.

It's not 100%, but it seems to be more than we hoped for. At least for covid, the viral load is reduced and infection depends on that.

> By far, the most widely studied trade-off involves transmission and virulence (Anderson and May, 1982; Frank, 1996; Alizon et al. 2009). Transmission and virulence are linked by within-host replication: increasing parasite abundance increases the likelihood of transmission, but also increases the likelihood of host death; mathematically, this assumption can be formalized by making transmission rate β an increasing function of parasite-induced mortality rate ν. Nearly all of the literature we summarize below assumes this trade-off.

https://www.cambridge.org/core/journals/parasitology/article...

Anderson, R. M. and May, R. M. (1982). Coevolution of hosts and parasites. Parasitology 85(Pt 2), 411–426.

Frank, S. A. (1996). Models of parasite virulence. Quarterly Review of Biology 71, 37–78.

Alizon, S., Hurford, A., Mideo, N. and Van Baalen, M. (2009). Virulence evolution and the trade-off hypothesis: history, current state of affairs and the future. Journal of Evolutionary Biology 22, 245–259.

Flip it around as well. Take for example Zika. When passed from mother to unborn it can cause various brain abnormalities. But perhaps eons ago a virus is what made homo sapiens more intelligent. If a virus can mangle the brain it can also nudge it in a positive direction.

Finally, human DNA is peppered with traces of viruses.

https://www.smithsonianmag.com/science-nature/virus-genes-hu...

Not only peppered, it's the main dish: 8% is direct viral remains, while other 40% have a viral origin.

Don't think it works like that. Nothing is stopping other viruses from infecting you while you are infected.

Actually it is: https://www.statnews.com/2021/01/31/a-viral-mystery-can-one-...

Viruses (or bacteria) don't "evolve to bypass" vaccines, antibiotics, or anything else. They generally have a pretty constant mutation rate, the vast majority of which are deleterious.

The more people that have a virus, the more copies are out there mutating, and the more mutations (in total) you'll see.

If you introduce negative pressure, like a vaccine or antibiotics, some of those mutations that were previously deleterious will turn out to be a net benefit. E.g: A thicker cell wall in bacteria makes it harder to absorb nutrients, but also increases the dose of antibiotic it can survive. These mutations happen all the time by chance, but in the absence of the vaccine/antibiotics, they are less fit and will tend to die off.

A vaccine that eliminates a virus is likely to result in less infections. Less infections means less mutations means less chance for a dangerous variant. If some variants do evolve that escape the vaccine, odds are good that they will be less dangerous than the original, not more.

This notion appears to go against all the expert advice against (ab)using anti-biotics. Sure, less infections means less chance for mutations, but due to the fundamental forces at play, the resistant mutations will spread faster through the resistant population and eventually become the prevalent strain.

Unless you can eradicate the virus or bacteria completely (mass effective vacination), the tools we create to fight them are really only delaying the inevitable.

>If some variants do evolve that escape the vaccine, odds are good that they will be less dangerous than the original, not more.

From my understanding, this is not the case. It's pure chance whether a mutation is advantageous or disadvantageous. If you are looking on a per-mutation basis, then sure, it's likely the mutation is disadvantageous. But at a population level, it's likely that atleast one advantageous mutation will emerge reasonably quickly when we are talking about something at the scale of several thousands of infections.

Seeing as we've wiped out multiple viruses completely, but have yet to eliminate any bacterial diseases, I believe there is an important difference between vaccines and antibiotics.

Perhaps viruses are simply more specialized, so it's easier to eliminate anywhere to hide by innocculating affected populations, while bacteria are more general purpose and can survive even without living hosts.

> Seeing as we've wiped out multiple viruses completely

If we're talking only human viruses, the count is 1: Smallpox, and it took about 20 years. If not, I think the count is 2, the other being a cat one.

In both cases, if I remember right, the virus couldn't jump species, while SARS-CoV-2 already has multiple times.

Yes, I thought we eradicated Polio, too. I see I was wrong. But apparently we are very close to eliminating a disease caused by a nematode parasite, too [1]. Fascinating.

[1] https://asm.org/Articles/2020/March/Disease-Eradication-What...

No. Just no.

Antibiotics do not treat viruses. They treat bacterial infections, which WILL mutate and evolve as you claim with overuse of antibiotics.

This does not apply in the slightest to VIRAL infections.

Antibiotic-resistant bacteria are bad not because they're more dangerous than regular bacteria, but because they are harder to treat with those antibiotics.

As for your second point - mutations are happening whether or not we vaccinate. Vaccination does not cause mutation.

It's already been observed in countries with a low infection rate. In the second half of 2020 Australia's death rate was below average [1]. Some people died from COVID, but more people lived due to due to anti-COVID measures reducing influenza.

[1] https://www.abs.gov.au/articles/measuring-excess-mortality-a...

Probably staying at home also reduced traffic accidents and other mobility related deaths.

Not traffic deaths, in the US at least (likely due to clear roads leaving people to drive riskier):

https://apnews.com/article/pandemics-health-traffic-coronavi...

Here, people started driving much more aggressively the first day of shelter in place and never stopped.

Not disagreeing, but a downside of isolation turns out to have been that, now we are effectively Covid free here in Melbourne, hospitals are filling up due to (sometimes serious) other diseases, including cancer, that people left untreated during the various lockdowns.

This is leading to very long ambulance waits at hospital entrances and lead to at least one death when an ambulance wasn’t available. (Sorry that I don’t have time to find a link right now)

To be clear I fully support the government action in Victoria, life is pretty much back to normal here, and looking overseas it seems hard to believe how fortunate we are, but it was not without unexpected consequences.

> but a downside of isolation turns out to have been that, now we are effectively Covid free here in Melbourne, hospitals are filling up due to (sometimes serious) other diseases, including cancer, that people left untreated during the various lockdowns.

This could really use some additional context for non-Australians.

Melbourne is the largest city in Victoria. The Premier of Victoria enacted interregional border closures during its several months-long lockdown.

(This wasn’t unique to Victoria — Western Australia did the same thing at the start of the pandemic.)

If hospitals are “filling up” now, that could be at least in part due to the logistics previously not allowing it.

However, as someone who avoided getting stitches for a finger laceration due to fears of catching Covid in a medical facility, I’m convinced people avoided necessary medical procedures to reduce exposure risk primarily. Hence I’m not sure how much of this surge in delayed medical procedures is due to interregional border closures, and how much of it is due to the public’s fears of catching Covid having been assuaged by the successful Covid safety measures taken by the Victorian state government.

Lockdowns have become one of the most politicized aspects of the pandemic. It’s really a shame they’re so unpopular amongst Americans: I think many there would happily subject themselves to 4 months of hard lockdown — in unison with generous unemployment support ofc — if it meant eradicating Covid completely in their local area.

It's not a shame at all. Lockdowns have a price. Besides the economic price, I care mostly about the well being of people price. I live in Massachusetts in an area where most people follow the guidelines about social distancing and masks. We had zero full lockdowns but we did have a stay at home advisory when it all started. During that time only essential businesses were open but people were free to go outside. Also, pretty much everyone besides essential workers moved to WFH and still are. Some schools had hybrid options and some were fully remote. This month almost all schools went back to fully in person after the governor of the state forced them to.

Overall I feel we managed the pandemic fine so far without lockdowns. Sure, people died and I'm sure in much larger numbers than Australia. But if we ever need to experience something like this again, I would still prefer this over strict lockdowns after a few new cases like in AU. I'm not against strict lockdowns, there might be times when they are a good solution, but nothing longer than a couple of weeks.

When you talk about the cost of lockdown, I suspect you don’t understand the deal.

My experience of Covid, which is the same for almost everyone in Australia, is nothing remotely like yours. For the vast majority of people living here, Covid is a minor inconvenience that doesn’t materially affect our day to day life.

I meet friends at bars for drinks and dinner, my kids take public transport to school and go on school camps, I go to the office for work, and I’m even flying to Sydney this afternoon for a couple of days.

Australia is basically operating normally with almost no restrictions. Situation normal.

You seem to be saying that lockdown was too heavy a price to pay for the freedom I now enjoy, but I respectfully disagree.

It was totally worth it.

The only thing that I’m unhappy about was that Melbourne stuffed it up the first time and we paid heavily for that. But you know what?

Still worth it.

Well, my life here is pretty much back to normal too. But primarily thanks to the vaccines. My question is how many lockdowns you had and the length of each lockdown to achieve the normal life you're having now. I'm really asking as I don't know the details.

In Melbourne, we have been basically running at increasingly normal pace for about 5 or 6 months now, but most of the rest of the country has been "normal" for much longer.

In Melbourne we have had three lockdowns, the first was a couple of weeks, the second was extremely long (several months; I think it was one of the longest hard lockdowns in the world), and the third was 5 days (2 of which were over a weekend).

Importantly, the second lockdown was due to what seems to have been preventable problems, including a significant delay before enacting the lockdown itself; by the time we did it, the virus had taken a firm hold across the whole city (Melbourne's population is a bit over 5 million). If we had locked down a few weeks earlier, the duration of lockdown would have been much lower (easy to say in hindsight).

That said, the rest of the county didn't suffer the same fate as Melbourne, and they only had to endure a few weeks of lockdowns at worst. I don't know the specifics from other states because I live in Melbourne.

I think this parallels most of the rest of the world: had everyone agreed to one or two really good, solid, early lockdowns, much of the pandemic could have been avoided. The countries that did this - NZ, most of Australia and I think some of SE Asia - have not suffered nearly as much as the rest of the world.

The second Melbourne lockdown was super hard on everyone, and of course we had government support in many (but not all) cases, but I still say it was totally worth it.

I just thought it was probably worth adding that Victoria (2nd biggest state in Australia) has recorded a total of 820 deaths from Covid. That's the total. Not per day or per week. 820 people died from CV in Victoria, ever. And we were the worst state by far.

People seem to be OK discussing hundreds of daily deaths from Covid as if that's something that can't be prevented, but it could have been. Our lockdowns have literally saved tens of thousands of lives here.

https://www.dhhs.vic.gov.au/victorian-coronavirus-covid-19-d...

While the lockdowns surely helped, you can't discount the advantage of being a non-densely populated island. Iceland and Japan, for example, also have very low death counts compared to mainland Europe or America.

Vietnam and Thailand would disagree.

Well, clearly if you have a very long and strict lockdown, you would have a low death count. If you optimize for that then nothing beats a lockdown. But everything has a tradeoff. If we optimized for low death counts then we would've banned cars long time ago. But instead we allow cars but try to prevent accidents as much as we can. And just to be clear, I'm not against short lockdowns when really needed.

Three months lockdown... is it worth it? Depends who you ask. If I had to go through such a lockdown in the US I would most likely move back to my home country or somewhere else. As for the rest of Australia (Sydney especially) and NZ - super impressive and totally worth it.

I can answer for Sydney. We had one "major" lockdown, which was still not as strict as most of the worlds lockdowns. Certainly at no point was it stricter than what my parents were experiencing in the UK.

Most shops were still open but had reduced numbers allowed inside. High risk venues like nightclubs and casinos were closed, restaurants went to takeaway only. This was early in 2020 when nobody knew what they were dealing with, really. They were talking about "Keeping numbers down until we can build capacity", but they just found out they were really good at keeping numbers down, and I don't even know what we did with our 2K extra ventilators when we peaked at about 60 patients in hospital in NSW I think.

We switched from a suppression to an elimination strategy and have been mostly normal since then.

One small group of suburbs had a lockdown around Christmas/New Years, but it only affected about 100K people I think and only for a few days.

The model in Australia seems to be to keep community transfer to zero, and if a case is detected, a 3 day lockdown of the suburb/city in question to let Contact Tracing and Testing travel faster than infections.

I'm in Sydney.

I've had one lock-down for about 6 weeks, starting on 30th March 2020. That's been the extent of it for me.

Lockdown meant the family stayed home with the children doing school remotely. We were allowed out for exercise (family group only) within a few km radius, supermarket shopping, medical and looking after aged family. I could have gone to an office, but was able to work remotely.

Other areas have been through more due to localised outbreaks. Parts of Northern Sydney did several weeks around Christmas due to an outbreak. Victoria's second wave was the most intense lock-down. That went for about 3 months. It was tough on the Victorians I know, but as a comparison at the beginning of the lock-down the UK and Victoria were in a similar situation. By the end of the lock-down Victoria was on zero cases whilst the UK was at risk of the NHS being overwhelmed.

We've now settled into a pattern of 3-day lock-downs at the first sign of any outbreak, these being lifted if there is no further transmission detected during the lock-down. So far there have been about 4-5 of these in different state capitals but all have been lifted at the end of the 3 days.

Vaccinewise, Australia's dropped the ball a bit. The government under spent on mRNA vaccines and didn't invest in local mRNA manufacturing. We're making the AZ vaccine locally, but there turns out to be a low risk of blood clots. Given the low COVID numbers it's borderline whether the risk of blood clots is outweighed by the risk of COVID for under 50s. The medical recommendation is for mRNA over AZ, but decent supplies won't arrive until the end of the year. I mention this as low COVID numbers makes decisions about vaccines more complicated.

Life here is "normal" in that there aren't many restrictions beyond overseas travel, but a significant number of people are choosing not to go back to their old ways, partly due to COVID risk and partly because they have figured out that some of their previous activities weren't actually that important and that life is good without them.

Very impressive that Sydney managed to do so well without a strict lockdown in the second wave like happened in Victoria.

Sydney/NSW is an interesting case, as its response has very much relied on contact tracing, to the extent that it is probably a world leader in this area.

When a case is detected, the NSW government's contract tracers conduct confidential phone interviews to determine all contacts, both forward and backward. A forward contact is someone to whom you may have given the virus. A backward contact is someone from whom you may have received the virus. The "backward" contact is the more critical one, as it can lead to previously unknown community cases. The contact tracers are aiming to trace the new case back to an already known case. If they find any intermediate transmission or close contacts, they recursively do the forward/backward thing on the intermediaries and close contacts until they reach limits imposed by COVID's known incubation and infection times. The aim is to locate every person who has any chance of having COVID, given the known properties of COVID.

If the contact tracers successfully traverse the tree to all possible cases then lockdown is avoided. Close contacts are required to isolate at home for 14 days (with a support payment), whilst casual contacts are asked to get tested and monitor for symptoms. If the contact tracers are unable to traverse the tree or are overwhelmed by the numbers then a lockdown occurs. NSW has put significant resources into contact tracing as it recognises that the cost of a lockdown will always be greater than the spend on contact tracing.

Beyond phone interviews, contact tracing is assisted by a requirement for all public venues to keep a 14 day digital log of names, phone numbers and time of attendance of people who have visited. Patrons provide details on an honour basis, but most people do this honestly as they realise that it is their own interest to be contacted if they have been exposed to COVID. There's also a certain amount of pride that the country has weathered the storm (so far) and people don't want to be the one that stuffs it up.

I flew back in to the country in March 2020, did two weeks isolation, and life has been normal ever since. When I visited my mother in the hospital in October, I had to wear a mask. Which they were handing out at the entrance because no one has them. That's it. That is the extent corona virus restrictions impacted me here living in Australia.

Now what they have done is kept me here living in Australia. Which has been a particularly big deal for my specific lifestyle in which I was living overseas in a dodgy visa abusing way, meaning I couldnt qualify for an exception to the international travel ban by showing I was legitimately living elsewhere. Day to day though its like it almost didnt exist except online.

> It’s really a shame they’re so unpopular amongst Americans: I think many there would happily subject themselves to 4 months of hard lockdown — in unison with generous unemployment support ofc

The unemployment support was missing/inadequate. Had it been adequate, I doubt we'd have had over half a million deaths from this.

America has poor control of its international borders and would be unconstitutional, not just unpopular, to lock down with a right of freedom of movement from state to state.

100% true. America does not have the luxury of Japan or Australia or New Zealand. Our border is very porous — just look at the whole “build the Wall” movement, and how laughably ineffective it was. The pandemic could never have been kept to 0 in America with its porous southern border.

The US has pretty much only two borders, as big oceans make for really good natural barriers.

If you want to see "porous borders" you only need to look at Africa, Asia or Europe, all of which can be walked in-between. Walking from the ME to America? Not gonna happen.

Crossing the Mediterranean is very doable with limited resources while crossing the Atlantic/Pacific with the same resources would be impossible.

> America has poor control of its international borders and would be unconstitutional, not just unpopular, to lock down with a right of freedom of movement from state to state.

It was also arguably “unconstitutional” [1] for Australian states to close their borders with one another over the pandemic. Business magnate Clive Palmer sued Western Australia over its border closures, in fact, and even received backing from the Australian federal government [2].

Particularly in light of the patchwork framework surrounding state-mandated church closures in the US, the difference between Australia and the United States as it pertains to interstate border closures seems to be more a matter of cultural expectation, than legal impossibility. But IANAL.

US airports are highly controllable ports of entry. I think a lot more could’ve been done there had the population willed hard border closures into existence.

[1]: https://auspublaw.org/2020/08/border-closures-and-s-92-clive...

[2]: https://www.theguardian.com/australia-news/2020/aug/02/feder...

For starters there’s how Israel does things, however, border closures were championed as xenophobic. Then there were those saying the US letting people (US citizens) in from China was problematic. The airports aren’t the major concern for points of entry, just take a look at the drug trade. Speaking of the church closures, those are unconstitutional as well as there’s rights to freedom of religion and the right to gather peaceably, except when there’s a virus apparently. The governmental powers are constrained and enumerated, and that doesn’t stop things since power is what power craves, and is really more of a speed bump now and seems like half the states support it at this point. Plus states choosing which Federal laws to uphold (Pot, immigration for example) is pretty fascinating.

As time passes so does the understanding of civics in the US. People think the President is like a king and just decree things willy nilly not appreciating the federal and state jurisdictions and that there aren’t departments which run things without direct intervention. Cheers!

I haven’t seen anyone talk about this, but I honestly believe that the fact that voting is mandatory in Australia contributed significantly to the legitimacy of government management of the virus.

More than half of the eligible voters in each state voted (either directly or indirectly through preference based instant runoff voting) for their government. This is significantly higher political participation than almost any other country in the world, and I’m sure it contributed to the outcome.

Yeah I agree that I should have chosen my words more carefully. It wasn't isolation that prevented people from getting medical treatment (you definitely could, and people did), but many related reasons: fear of contagion, a desire not to burden the front line people, lack of access (public transport restrictions), procedural changes (not allowed to have someone with you), etc.

So I don't think the current situation is a result of iso but rather a result of Covid, and the fact that we are no longer fearful of it.

Resistance to the COVID approach you admire extends beyond the USA to also many in UK and Europe. The problem is that even if a hard lockdown works and COVID is completely eradicated in one’s local area, that means that the borders have to stay closed lest new cases be imported. But many people have families or lovers across borders, they might even commute or do common shopping cross-border, and the lower and middle classes cannot afford the expensive hotel quarantine required. Tourism-based economies need travelers bringing all that money in.

(One might think that borders would only have to stay closed until local vaccination has been rolled out. However, several of the scientific advisors recommending the "zero COVID" approach à la Oz and NZ, also want borders closed – except for strict hotel quarantine – for some years into the future to prevent variants from arising, or even in perpetuity to prevent the next pandemic from ever starting.)

I’ve never heard of this idea that borders are supposed to stay locked shut indefinitely, and the facts suggest otherwise: the international border between Australia and NZ has reopened, there is no quarantine for international travel between our countries.

In the case of Australia and New Zealand, travel has reopened only because both of those two countries managed a successful early lockdown and adopted a "zero COVID" approach. But since most countries in the world did not, those living in the "zero COVID" countries would be prevented from freely traveling to all those countries to see loved ones.

With regard to the proposal that borders stay closed – except for strict hotel quarantine – until some indefinite date a few years from now when COVID has been eradicated not just locally but worldwide and there is no more threat of variants, see, for example, the interviews which Devi Sridhar (one of the main advisors to the Scottish government and a fan of Australia’s approach) gave over the last several months.

> those living in the "zero COVID" countries would be prevented from freely traveling to all those countries to see loved ones

Not true. There's repatriate flights weekly out of both NZ and AU. You just have to quarantine coming back in.

There's a process for approval, but it's fairy straightforward. If you can afford a ticket and the destination country will take you, you can go.

The hard part is - most countries or connecting countries if you can't fly direct require 2 week quarantine or limit people entering. ANY inter-country travel is a bureaucratic nightmare.

> There's repatriate flights weekly out of both NZ and AU.

What if you are not taking a "repatriate flight", but rather you are simply an Australia citizen who wishes to travel abroad e.g. to see family or be with a lover? My understanding is that Australia has forbidden its own citizens from freely leaving the country over the last year.

And having to do a strict hotel quarantine upon reentering definitely does not qualify as being able to freely travel, and as I said in my original post above, many people would not stand for it. Most European countries that require quarantine, for example, allow one to do it at home and it is easily gamed.

Yeah I am sorry but have no idea what point you are trying to make. Which freedom do you want - freedom to travel, or freedom from death?

Freedom to travel. From my European perspective, COVID deaths suck, but we cannot return to hard borders. It risks reigniting old nationalist conflicts and it undermines Europeans’ ability to join together and meet 21st-century global challenges. We need people frequently crossing the border for work, shopping, and leisure, so that they interact with their neighbors. We need young people starting relationships with people in other countries and raising families. While there have been some restrictions on movement in Europe in the last months, they have generally never been too strict. And thankfully they are being lifted now, much earlier than the aforementioned extreme wing of public-health advisors advocates.

Australia’s policy of a hard lockdown followed by strict hotel quarantines worked for Australia, but it wouldn’t work here, and it is always tone-deaf when Australians recommend it as some kind of universal solution.

The issue in the UK isn't just families and lovers: It's also that we rely on cross-channel shipping to keep our supermarket shelves stocked and our businesses operating. 10,000 lorries a day, in peak periods.

And a mere 48-hour disruption had pretty disruptive results [1] - and week-long quarantines simply aren't an option.

[1] https://www.bbc.co.uk/news/business-55389505

It's not like the same didn't happen 'over here'. Canada for me specifically but even though we didn't lock down as hard as you guys did, the same thing happened with regards to other health procedures. People not going for cancer screenings. Not dentist visits etc.

In fact, there was one particular story on the news that I remember the most about a woman who couldn't get her appointments for an eye treatment due to the lock down and it progressed from curable to incurable.

She's blind now.

As I understand it, the resurgence of interest in mRNA research has already raised hopes with respect to HIV and (I think, some forms of?) cancer. So yeah, much like a lot of life-saving technology is created in response to war, there might be a silver lining here.

In fact, Biontech, the actual company behing the "Pfizer" vaccine was doing cancer research with mRNA and switched to vaccine development "to help out" because they realized that their tech could be used in this way too.

Same with Moderna.

One thing to note is that mRNA therapeutics are a really tough area in part because:

1.) RNA and the lipids used to get it inside a cell are inherently pretty immunogenic (a huge plus for a vaccine). If you think about it, you basically never see free mRNA/DNA in the blood stream other than if something has gone wrong (usually a virus), so the immunogenicity here is pretty ancient.

2.) RNA gets shunted to the liver and chopped up. Hence most RNA based therapeutics target the liver.

Vaccines are a really great use case, not just a, "we could help out here too," side-case. They're delivered intra-muscularly so there's less "go to the liver!", and the immunogenicity is a feature not a bug.

Lots of this comes from siRNA therapeutic research that is older than mRNA work, but the principles are very similar. Some older articles that touch on some of these issues:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378126/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269031/

https://www.sciencedirect.com/science/article/pii/S016836591...

Free DNA is not exactly uncommon. Apoptotic cells release DNA into their environment all the time. As another example, free foetal DNA in the mother's bloodstream is how NIP tests can operate.

It has very short half life, there’s not a ton of it and it’s likely to be wrapped around a nucleosome. Uniformly, sequences in blood are quite short (<200bp) which is far too small to code for anything meaningful (for reference COVID genome is 29kbp, and the spike protein version in the vaccine is about 4kbp). The bloodstream shreds free DNA pretty effectively, but yes, some short DNA can be detected. That’s a good bit different than a large amount of mRNA/DNA floating around though, especially if it’s a long sequence.

Useful reference:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715266/

I’ll be interested to see how well we predict the externalities of eliminating a species of microbe or insect that we consider a pure pathogen.

>I have wondered if the COVID-19 pandemic might lead to some results, like extermination of the common cold, that humans would look back on and say that it was a net benefit.

I'm not sure if you could attribute COVID-19 to such a success. Several highly skilled teams are working on this and other concerning diseases like Tuberculosis (independent of COVID).

Yes, but many of new therapies, such as mRNA vaccines, were slow to receive approval, and have been sitting on the drawing board for a decade

Sure, but maybe the flu isn't the best example. I'm long MRNA and big fan of the vaccine's technology. It was a biochem nerd dream getting my first shot!

Agreed, but it was given a temporary emergency approval due to the pandemic. We need long term data on technologies before we immunize hundreds of millions of people with it.

Huh? How many millions have been immunized so far with it?

What question did you have for me? I see your comment as a statement.

The point is clear you said

> We need long term data on technologies before we immunize hundreds of millions of people with it.

But we have already done this, hundreds of millions of people have received the mRNA vaccines.

We don't have long term (5+ years) data though, which was my point. It was authorized as an emergency measure due to the pandemic.

OPs point is that because of covid-19 we quickly threw trillions (?) of dollars at the problem, and without covid-19 the funding/attention/determination/man-power etc would be much less.

I probably read too much into their usage of the flu as an example. But yes, mRNA will lead to benefits beyond COVID. Some of the computational techniques developed for COVID will likely assist other drug discovery and development processes.

I suppose you could attribute that more to humans sucking at taking action until shit actually happens.

The common cold cure could have happened without COVID, but nobody cared to fund it until COVID happened and then they went "oh shit maybe we should actually fund medical research".

There is incentive to not cure mild diseases because more money can be made on palliatives.

Or the money can be used to research more serious diseases.

> ...common cold.

The common cold is a tricky one because it's about 200 different viruses, including rhinoviruses, coronaviruses, RSV and parainfluenza. And a bunch more that haven't been identified yet.

200 pills then

We've found that you can safely take approximately 28 pills per day. You'll be through this innovative course in just under 7 days!

So you can immediately cure 1/7 of patients, and if we analyze what strains are in the area we can rapidly get that above 90%? Sounds good.

That would be fine if we combined it with expanded rapid testing. Spit in a tube, get a pill that cures your specific virus.

"The most commonly implicated virus [in the common cold] is a rhinovirus (30–80%). Other commonly implicated viruses include human coronaviruses (≈ 15%), influenza viruses (10–15%), adenoviruses (5%)." [1]

So yeah, this wouldn't be a cure for common cold. Maybe it could be a pill people could take with a 10-20% chance of curing it, if they're lucky.

[1]https://en.wikipedia.org/wiki/Common_cold#Viruses

Are you assuming that this antiviral only works on coronaviruses? Maybe that's not the case.

Yeah its a good question; my understanding is that unlike antibiotics, broad-spectrum antivirals don't really exist. [1]

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103698/

The article was pretty clear about that in my view, yes.

My infant daughter just wrapped up a run of about three or so weeks of “a cold.”

After the second week, a handful of Covid tests, and one fever, we took her to the doctor and asked why this cold was lasting so long.

Our pediatrician was like “not cold, colds. She probably had 3-4 viruses back-to-back.”

I had no idea this was a thing - he called them “daycare viruses.”

In 2019 my infant son had a 3-month period where he was sick at varying levels for 100% of the time. We kept thinking it was some kind of resurgence, until an epidemiologist at the hospital explained to us that he just kept getting different viruses from daycare over and over.

The year of sickness, what I call our daycare episode. During that time I heard the GRC podcast about vitamin D3, started taking it, and haven't been sick more than a day or so since.

I am supplementing vitamin D3 and I still get sick. It is not a silver bullet for immunity.

Probably your kid has by the time you started supplementing just gone through the typically circulating virus strains and thus the viral loads in your kid don't replicate to levels that almost guarantee you being infected when interacting with them (like cuddling, comforting when they cry, etc.).

It's approaching ten years, and yes we have seen just about every strain. It stopped the winter week I started taking it.

As I said I sometimes get sick every few years but one day is typically the maximum. Consider me convinced.

Yeah, it is pretty nuts how sick kids get in daycare, although our pediatrician says it is training their immune system. She said that for kids not in daycare, the same thing happens once they hit kindergarten.

First few months of daycare, constant colds. Then COVID hit and we took the kids out of daycare, no colds for months. Back at daycare, colds started right away.

It has mostly stopped for my five year old. She gets a normal amount of colds now (a few per year), but our two year old is still a constant cold machine.

For us it mostly stopped at age 3 (starting daycare at 2). Of course our daughter still gets sick now and then but fairly low-frequent. First year was rough though.

Oh boy, welcome to parenthood. Having young children in daycare or school means a constant stream of virus infections for the whole family. I don't remember when it started to trail off, but probably when my youngest got to about 7 or 8.

Yeah, we have a toddler right now too, and if I’m estimating, during the months of October - February over the last three years I would guess I’m at least a little sick half the time.

The one that shocked me was rotavirus. At the time my kids were little it wasn't part of the regular vaccination regimen here in Ontario yet, was optional and our doctor didn't tell us about it. The kids both got it at the same; wasn't a huge deal for my son who was still breastfeeding, just had some diarrhea. But my daughter is three years older and couldn't keep food down for many days and lost a few pounds was very unwell. Awful.

Both our kids had stints in an isolation ward being fed/hydrated through a tube with rotavirus at ages around 3-4. They couldn't even hold down small amounts of water for days. I could see how it kills so many kids in developing countries without access to that.

I also wonder about this. They say that children who grow up on farms have stronger immune systems because they are exposed to the natural environment more. Weirdly, they also have low incidence of food allergies.

Do children who attend daycare eventually develop a much stronger immune system? (No idea how this could be scientifically measured.) I also wonder about doctor's who work in the emergency room. How are they not constantly sick with some kind of common cold / flu / bronchitis? They must have the immune system of a super hero.

Children who grow up with dogs and cats are also less likely to have allergies and asthma. [1] Lovable little filth monsters drag in all sorts of stuff, I guess haha.

[1] https://www.webmd.com/allergies/news/20180716/can-dogs-keep-...

Sadly pets and farms still aren't a cure all. I grew up/live on a farm with cows, cats, and usually a dog. I've got a lot of environmental allergies and a few food ones, and my day to day symptoms can be pretty bad, especially this time of year. Oh well, who knows how much worse I'd be if I hadn't grown up on a farm.

> They say that children who grow up on farms have stronger immune systems because they are exposed to the natural environment more. Weirdly, they also have low incidence of food allergies.

I have many siblings (more than 9). All of us grew up on an active farm except the youngest one. None have had any food allergies except from my youngest brother.

> I also wonder about doctor's who work in the emergency room. How are they not constantly sick with some kind of common cold / flu / bronchitis?

A colleague of mine told me his wife would eat anything that had expired best before date etc while she was in training, just to build her defenses.

I cannot vouch for this theory but maybe someone else can tell if it is a common tactic.

(I think it sounds weird.)

> A colleague of mine told me his wife would eat anything that had expired best before date etc while she was in training, just to build her defenses.

I lived for 5 years in a college dorm sharing bathroom/toilet and a communal kitchen with 14 other students. I am not quite sure it built up my immune system. I managed to get the swine flu back then, too.

This reminds me of another dorm story, a friend of a roommate always washed his hands when he came of the bus and visited. And I distinctly remember how we all felt that this was somewhat weird, obsessional, when in retrospect it just feels prudent and I don't really think he showed signs of pathological obsession. Its interesting how standards change.

As to eating stuff past expiry date: my wife tends to stockpile yogurt and dairy products in our fridge, not that uncommon that they were past their date. Turns out, since they are pasteurised they are often still good weeks after their best-before date. I actually don't think there is much in them to train your immune system (unless they are spoiled and I don't think fungal toxins is something you voluntarily want to put in your body).

Best-before dates aren't meaningful.

> Contrary to popular impression, the current system of food product dating isn’t really designed to help us figure out when something from the fridge has passed the line from edible to inedible.

> For now, food companies are not required to use a uniform system to determine which type of date to list on their food product, how to determine the date to list or even if they need to list a date on their product at all. [1]

[1] https://theconversation.com/how-do-food-manufacturers-pick-t...

> Do children who attend daycare eventually develop a much stronger immune system?

I would say so, yes. Your body remembers what viruses it's already fought, and will remain primed (for a significant time) to fight it again. Kids exposed to lots of illnesses when young, should end up with a more robust immune system in adulthood.

This is why chicken pox parties are a thing.

I'm sorry to hear about your daughter's illness. I hope she has recovered well.

Did the doctor's test for respiratory syncytial virus (RSV)? I only learned about that illness recently. Interestingly, there have been multiple, failed attempts to build a vaccine. It is one of the last statistically significant childhood viral illnesses without a vaccine in highly developed nations. I wonder if an mRNA solution can be found after the COVID crisis is over. I sincerely hope so.

Ref: https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

Aside: I’m a native speaker of American English, and in all my years of reading and conversation I’ve never seen or heard the word “schtum.” Is it a regional thing?

> Borrowed from Yiddish שטום‎ (shtum, “mute, dumb, voiceless”), from Middle High German stum, from Old High German stum. Cognate with German stumm, Dutch stom, Swedish stum. [1]

[1] https://en.wiktionary.org/wiki/shtum#English

The funny thing is that in Slavic languages, the word for a German translates to "the mute one". For example, NEMec in Slovenian.

Mute, because he can't speak our language.

I've wondered why we have a different word for Germans but never realized that's where it comes from (if it's true).

I only knew it from Hungarian, which I guess is a slavic enough language to compare: https://en.wikipedia.org/wiki/N%C3%A9meth:

In Hungarian, német means "German" (the word has Slavic origin, literally meaning "he does not speak", since German is not a Slavic language)

Hungarian isn't Slavic.

The word is probably borrowed into Hungarian from Slavic. We have a similar word in our language as well, but it's used as someone who doesn't understand. Also used interchangeably with Turk.

Do you mean Barbar?

No, it's very similar to nemec, basically the same thing also borrowed from Slavic. The "c" ending is pronounced as "ts". The full phrase goes like: "Why don't you understand, are you German/Turk?" (as in not understanding the language). There's also a place, a citadel and river with that name, which your ancestors might have been familiar with:

https://en.wikipedia.org/wiki/Siege_of_Neam%C8%9B_Citadel

Barbar means what it means in Greek, because that's where it's borrowed from.

Similarly, the word "barbarian" comes from the ancient Greeks describing the people who lived around them as sounding like they were saying "bar bar bar".

Funny, I always thought it came from the word Barba (hair/beard) because they considered them uncultured and unshaven.

Greeks were into beards big time.

That's amazing. Wiktionary backs you up on this and compares it to "bla bla bla".

https://en.m.wiktionary.org/wiki/%CE%B2%CE%AC%CF%81%CE%B2%CE...

It is true. Here's a map of what Germany is called by other countries in Europe: https://jakubmarian.com/wp-content/uploads/2016/08/germany-e...

Interesting that Finland/Estonia call them, essentially, Saxony.

The Latvian/Lithunian name for Germany is the only one I don't understand. Does anyone know?

According to Wikipedia [1], it’s a matter of some debate, with the theories being the (standard) corruption of a name for the first Western Baltic people encountered, or a take on the “unintelligible war cry” people from the Latvian root for speaking.

[1] https://en.wikipedia.org/wiki/Names_of_Germany

Apparently it's most likely tied to the German municipality of Waake or the Swedish tribe of Vagoths. However most Lithuanians would likely explain it in the form of a joke - either about Germans being thieves ('vogti' = to steal) in reference to Teutonic/Livonic ordins, or about them being 'tough' or well armored ('vo kiets' ~= 'wow, tough/hard').

Another fun fact: at least in Croatia, we colloquially call them "schwabs" which originates from another group of germanic people https://en.wikipedia.org/wiki/Suebi

Can confirm (as a Slovenian), the term is used through the Balkans. For example, it is present in the old Serbian song:

Četrnaeste, četrnaeste, Švaba udario, (2x) Osamnaeste, osamnaeste, Srbin pobedio. (2x)

(In the 14th year, the Schwab struck. In the 18th year, the Serb won.)

https://hr.wikipedia.org/wiki/Ko_to_ka%C5%BEe,_Srbija_je_mal...

It comes from the fact that Germany didn't unify until very late, so the people were called by the small city-states that they came from. In American revolutionary war, some British mercenaries were called Hessians....

In Russian, at least, the country remains “Germany” but the people from it are the “mute-sies”, unlike pretty much every other pairing of country name / demonym.

In Italy Germany is Germania, but Germans are tedeschi and German (the language) is also tedesco. (BTW, we lowercase people and languages and weekdays and months, but this is changing - English leads.)

The reason seems to be the Latin word theodiscus from Old German theod / people.

Interesting tangent, but I believe this is also a slavic surname and is anglicised as Nimitz. And before you know it you have an aircraft carrier called USS Mute.

I don't think the other reply answered the question. Google trends show 10x as many queries from the UK than US for "schtum". So I would guess your intuition is correct.

I've never heard of it either. Grew up in the midwest, lived on the west coast.

I guess you could say we've been keeping schtum about it.

Fairly common in UK English, particularly in London which has long-term Jewish community.

It's slangy and self-consciously borrowed, like 'schlep' or 'schmuck' in New York English.

I was born and raised in the UK and have never heard of it. No Jewish friends or family though.

Definitely a thing in the UK : http://www.bbc.co.uk/comedy/onlyfools/lingo/

Very much a London-centric word, originally. And it seems like people of a certain age heard it all over the country on telly.

Ahhhhh, I had to look at the byline carefully. This article is syndicated from the The Telegraph.

https://www.telegraph.co.uk/global-health/science-and-diseas...

Which explains the British idiom in a Anglo paper in a bilingual city in Canada. (Bonjour-Hi!)

It's a perfectly cromulent word.

https://www.merriam-webster.com/words-at-play/what-does-crom...

Without any context, Apple’s Dictionary lookup serves up the definition of “cromulent” from both OED and New OED entries. It was apparently added in 2017 according to a Reddit thread, and in 2018 according to this list: https://public.oed.com/updates/new-words-list-june-2018/

Merriam-Webster added “embiggen” but declined to add “cromulent”: https://www.bbc.com/news/newsbeat-43298229

Common in the wider Jewish community in the UK. Universally understood now by most british people. In widespread use. Was in Monty Python, back in the 70s.

https://en.wikipedia.org/wiki/Yiddish_words_used_in_English#...

I'm a non-native English speaker and has heard it used many times. But since I'm Swedish it's also instantly understandable for me and so easier to remember maybe.

I'm Swedish and have never seen nor heard "schtum" before.

Guess "keeping quiet" didn't come to the author's mind. /s

And it didn't sound the least bit familiar from any similar Swedish word...?

Of course it does, given that there is a cognate Swedish word. I still have never seen "schtum" in English before. Maybe I'm just a schmuck.

Ett kutterschmycke.

CO2 is a good proxy for airborne infectious disease risk. Outdoor air is 400 ppm or so, best practice in modern building going into the pandemic was 600 ppm. Get CO2 down to 450 ppm and airborne infectious disease transmission plummets.

We have varied reactions to parts of the world that still suffer the consequences of human waste in irrigation water. In the far future people will view our current indoor spaces with similar varied reactions.

That's cool and makes total sense as a measure of how "ventilated" a room is, though I'm sure it has its limits.

I assume just installing CO2 scrubbers would have no benefit though, since the CO2 level is just a proxy for how much the air is recirculating.

Exactly. A proxy.

Unless you use high quality HEPA filtration (and/or UV sterilization?) as well.

Yes that increases air quality but it would not add oxygen back into the air in place of CO2.

Oxygen depletion doesn't seem to be the issue though, CO2 toxicity does.

At 1400ppm CO2, we've turned what, 1000ppm O2 into CO2 (is it 1-1?), or 1% of the atmosphere. Dropping O2 from (Edit: Fixed numbers) 21% to 20%. Or about a 5% reduction in O2 density. Equivalent to approximately 1500 feet of elevation... That's just not that much.

(There's also a long list of papers showing issues with CO2 toxicity at low levels of CO2... I keep intending to write a blog post summarizing them)

>Dropping O2 from 30% to 29%

Dry air is ~21% oxygen by volume.

Ah, oops, you're correct of course. The general point still stands though (at 5% instead of 3% and 1500 feet instead of 1000)

I'm getting the density numbers from here by the way if you want to check the rest of my math: https://www.engineeringtoolbox.com/air-altitude-pressure-d_4...

30% O2 in the atmosphere? Mayve when dinosaurs roamed the Earth. We currently have about 21%.

> At 1400ppm CO2, we've turned what, 1000ppm O2 into CO2 (is it 1-1?), or 1% of the atmosphere.

1400ppm is 0.14%. Earth's current atmospheric co2 level is around 400ppm, or 0.04%. While the jump from 0.04% to 0.14% might seem significant (3.5x more co2!), it's not.

Submariners survive on 3400 to 11300 ppm co2, or 0.34 to 1.13%:

> Submarine crew are reported to be the major source of CO2 on board submarines (Crawl 2003). Data collected on nine nuclear-powered ballistic missile submarines indicate an average CO2 concentration of 3,500 ppm with a range of 0-10,600 ppm, and data collected on 10 nuclear-powered attack submarines indicate an average CO2 concentration of 4,100 ppm with a range of 300-11,300 ppm (Hagar 2003). [0]

[0] https://www.nap.edu/read/11170/chapter/5

I'd like to emphasize that the average CO2 concentration for submariners is 4,100 ppm or 0.40%, or ten times Earth's current CO2 level.

Oxygen is much more toxic than small amounts of CO2. Pure CO2 will kill you quickly, pure o2 will kill you slowly.

> (There's also a long list of papers showing issues with CO2 toxicity at low levels of CO2... I keep intending to write a blog post summarizing them)

I'm interested.

Oops, today really isn't my day for math apparently :(... 1% did seem high.

---

> I'm interested.

Well I don't have a blog post ready to go yet, but I can point you to some papers now.

- This review cites a bunch of papers about health effects in the 1-10k ppm range: https://www.nature.com/articles/s41893-019-0323-1.epdf?refer...

- Table 3 in this paper references a bunch of papers around 10kppm: https://www.researchgate.net/profile/Susan-Rice-3/publicatio...

- These papers show mental effects in the 1-4k ppm range:

https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.1104789

http://www.aretas.ca/sites/default/files/imce_images/Indoor%...

- These two are from nasa about the ISS - which brings it's own complications but otherwise also show mental effects in the above range

https://web.archive.org/web/20190613133240/https://ston.jsc....

https://pubmed.ncbi.nlm.nih.gov/24806559/

Thanks for the links, I have started perusing them.

As someone pointed out in a reply to another comment in this thread, oxygen is especially toxic 33 feet below the surface of the water (because of higher pressure), but can have toxic effects at the surface too. I don't grok respiration yet, but my understanding is that altitude/pressure is essential for putting the relative N2/O2/CO2 partial pressures into context.

1) How is something that kills you slowly more toxic than something that kills you quickly?

2) Don’t doctors provide severe COVID patients with pure oxygen? If it’s toxic, why would they do that?

3) How does pure oxygen kill you? What’s the mechanism?

> 1) How is something that kills you slowly more toxic than something that kills you quickly?

Pure CO2 will knock you out in 4-6 breaths, and cause your expiration in 10-20 minutes. Laboratory animals are routinely euthanized with co2 [0]. Pure O2 will cause your expiration in 4-6 days through the accumulated damage of reactive oxygen species.

[0] "Expose the animals to CO₂ until complete cessation of breathing is observed for a minimum of 2 minutes (a total of approximately 5 to 10 minutes is usually required)" - https://www.bu.edu/researchsupport/compliance/animal-care/wo...

> 2) Don’t doctors provide severe COVID patients with pure oxygen? If it’s toxic, why would they do that?

This is bad medicine. Early 20th century medical investigators figured out best practices for oxygen support, but the insights got forgotten, now they're just in the old papers in the libraries.

> 3) How does pure oxygen kill you? What’s the mechanism?

tl/dr: Hyperventilation.

> How does pure oxygen kill you? What’s the mechanism?

Oxygen is highly toxic to the cells in the human body, but not generally under standard atmospheric pressure. Breath pure oxygen while >33ft below water and you’ll quickly experience oxygen toxicity, ultimately leading to death. Yes, that’s generally specific to divers, but even pure oxygen at standard atmospheric pressure can have health impacts.

More information: https://en.m.wikipedia.org/wiki/Oxygen_toxicity

I’ve thought a lot about CO2 scrubbing of indoor air. Oxygen concentrators are cheaper than air scrubbing and much easier to do regeneratively. The simplest and cheapest scrubber is to just use sodalime, but that’s disposable and single-use. A regenerative system that heats up the lime (and vents the CO2 elsewhere) is more complicated and expensive and very energy intensive. Other solutions using amines or other chemicals to remove the oxygen can be more efficient, but many of them don’t work efficiently except at higher CO2 concentrations.

We are, of course, talking about miniaturizing a Direct Air CO2 capture system, which usually operates at large scale to get efficiency. Replaceable cartridges that are regenerated at a central location may be a better option.

But oxygen concentrators are small and cheap and portable and don’t require much energy to operate.

You can use ozone generators instead of UV. There is actually a really good residential one that is self cleaning my own HVAC guy recommended.

He recommended I buy it myself on amazon and linked me to a youtube to install it: https://www.iwaveair.com/products/iwave-r

He said that his company would install it, but they'd overcharge and it is easy for anyone to install themselves. He had one in his house and told me all about it like a sales pitch. I installed one not because of the coronavirus, but because it helps with particulates in the air such as pollen and dander, which absolutely wreck me. I've only had it for a year, but it does seem to be noticeably better allergy-wise.

UVC also generates ozone as a byproduct but it's toxic and it damages the lungs.

https://www.epa.gov/indoor-air-quality-iaq/ozone-generators-...

Do read the warning from the EPA.

That one specifically says it ionizes without creating ozone.

That's a good thing, because there is no safe/acceptable level of ozone in indoor air:

https://www.epa.gov/indoor-air-quality-iaq/ozone-generators-...

Ionizing can be a great way to remove fine particulate from the air, but it works best when there are charged surfaces for the charged particles to plate-out on. Simply ionizing them in the ductwork means the particles stick to whatever's handy, which may be the ducts, may be the furniture, may be your lungs.

Which is to say, this product uses a lot of the right vocabulary, to describe precisely the wrong engineering.

I have never heard of a building with a CO2 scrubber. Submarines and spacecraft, perhaps.

HVAC engineer here. Correct - and the reason that ventilation is currently limited in buildings is to reduce energy loss. Exhausting warm air in winter or cool air in summer is enormously resource intensive for a building. Depending on the building configuration, you can reclaim some but not all of that energy by using heat exchangers, where the exhaust and supply air streams exchange heat without mixing but then you impose an energy penalty via increased pressure on the ventilation fans in mild conditions when the heat exchange is of less benefit.

So all the standards and codes are designed around reducing unnecessary ventilation and frankly, there's been very little consideration of the health implications until COVID hit.

If you would be building a new house and willing to spend double the usual on HVAC, what would your focus be on?

The perhaps non-intuitive answer is - everything that reduces the need for HVAC. I'd be looking at things like passive solar design so windows are shaded in summer but let sunlight in for heat in winter. Very good insulation and building sealing. Double glazing (possibly triple if you're in a very cold climate). Thermal mass in the right places for temperature stablity.

On the HVAC side, you want a system with a high CoP and I'd probably be looking at some form of energy recovery on the ventilation side.

Yup, very much so: https://www.treehugger.com/praise-dumb-box-4853131

I live in a relatively new building in NL, where many of these configurations are applied and on its own it won’t go lower than 21C in winter and 25C in summer. Thick walls, thick anhydrous cement floor layer for insulation (although I think it’s also meant to give the option to implement floor heating), _external_ blinds on the South side.

I simply can’t justify a smart thermostat/radiator valve build, despite my inside nerd constantly whispering I should.

Only downside is the heat exchanger air recirculator: it dries the air terribly in winter. You need a humidifier to avoid getting parched skin and mucosa.

What if you wanted good ventilation/co2 levels?

With modern construction, active ventilation is a requirement. So sizing that for the intended turnover would probably be all you would need to do.

> everything that reduces the need for HVAC

This is the answer! Even more important than insulation is air sealing, so you keep the conditioned air inside.

I've learned an enormous amount about building efficiency from

https://www.greenbuildingadvisor.com/ and https://www.energyvanguard.com/

If you are in a temperate climate, like The Bay Area, looking into hydronic heating.

I installed it, and would never go back to forced air. For some reason, it's not popular on the west coast.

It's so simple, a DIY'er could do the instal.

My energy bill is down, and allergies are better.

(I've noticed every store I have been in has forced HVAC, and I have a weird feeling forced air spread viruses. Plus--most retail stores have old systems. They might have slapped in some high mir filters, but I doubt they help with anything on old leaky systems.

(To those interested in hydronic heating, buy Modern Hydronics, by Stegenthal? I'm too lazy to look up his last name, but his book is used as text books.

For anyone else wondering what hydronic heating is, it's using warm water as your main heat source. Either using radiators, or tubing in the floor to heat a room.

This contrasts against the more common American method of using hot air to heat a home. I believe air heating is more common in the US because AC systems already require the relevant air ducting, so it's easier to install.

Meanwhile here in NL airconditioning is very rare, and 95% of people use a gas fired water heater and metal radidators in rooms for heat distribution.

i would go as far as to say that nobody in continental europe knows the term 'hydronic', it's just heating, maybe central heating.

TIL:

- The term hydronic heating.

- That most Americans don't have hydronic heating.

That's so weird, here in France radiators are just ubiquitous.

This is the detachable showerhead thing all over again. How do you people survive like that? You're supposed to be the highest GDP country in the world!

It’s because most AC systems require forced air, so hydronic is a second system.

You’ll find hydronics in expensive houses that can justify the double expense or in colder climates where the heating benefits are more important than AC.

Also everyplace I’ve lived in the last 25 years has had detachable showerheads.

You'll find radiators in many older buildings (before about 1930 or so, at least in my area). Some are steam and some are hot water. The problem with them is that they tend to have higher maintenance costs plus if you wanted AC, you'd need to have a separate system, including ductwork. AC is relatively cheap to add to a house with forced air heating and quite expensive to add to a house with radiators. Mini Split AC systems are changing that somewhat, but they haven't caught on too well here.

You can also find baseboard heating, but that tends to be electric and have quite expensive operating costs. It's mostly only used in additions and places where you would only heat the space if you were currently in the room.

> This is the detachable showerhead thing all over again.

Uhhh... Everywhere I've lived in the US has had a detachable showerhead, from places built in the 1890s to places built in the 2000s. It's a normal thing for apartment dwellers to buy a nicer showerhead to replace the likely cheap and crappy one that landlord installed and then put the crappy one back before moving out.

I looked up the last name: Siegenthaler

Modern ventilation hardware can reclaim between 85-95% (claimed, but tested and verified). You do not need to run it full power, just a constant optimized flow and only when people are actually in the rooms. I'm relatively sure that the cost is less than heating/cooling a poorly insulated house.

> Get CO2 down to 450 ppm

And buildings will be much more pleasant. It's possible that people would be smarter, too (as opposed to being shut up in a badly ventilated conference room for an hour or two).

There are costs, as heat or/AC will have to run more to keep the temperature in the right range.

Counterflow air-to-air heat exchangers mitigate much of that cost.

I knew about residential ones but it looks like there are commercial ERVs as well: https://www.york.com/commercial-equipment/air-systems/energy...

Also widening the range would be a reasonable thing. Wear a jumper in winter. Don't be forced to go from 40C to 20C in summer. We don't need precisely the same temperature 24/7, 365.

Many* places normally don't have the same temperature since people do wear jumpers in winter and less clothes in summer.

Buildings are often (not always) set to 24-25C in summer, and 21-22C in winter.

*no figures sorry, just in my experience

At my office the climate control is considered adequate if it is 68 or above in winter, and 78 or cooler in summer.

20 Celsius / 25 Celsius.

I find anything over 22C too much for intelectual work. So, I am glad I WFH

Heh, I find it uncomfortable under 25C.

My wife and I live in Hungary. Every so often we visit Phoenix, AZ in the summer to see family. (My wife is a teacher so it makes sense to go in summer) and the hardest thing for us to do when we go out to eat is finding a restaurant that has seating where we are not freezing cold. It will be 40+ outside and 20 inside.

Yeah, regrettably, the American practice seems to be to overchill in the summer and overheat in the winter. This is also done in the home to the point that people will wear shorts and tshirt indoors in the winter and warmer in the summer (blankets while watching TV for example). Also office buildings suffer from the same problem. Women usually complain the most about it being too cold (men are more likely to wear suits and generate more great I believe).

That is probably partly explained by (at least in older houses without reflective insulation) low radiant heat from outside in the winter, and high radiant heat from outside in summer.

And different humidity explains it some too, even though AC lowers humidity, indoor humidity is still much lower in winter.

I've joked for years that the hotter the place in the US, the colder they keep their AC in the summer.

So many times I see the opposite: of its hot out then people crank the AC to coldest setting and if it's cold out then crank the heat up uncomfortably high. It drives me nuts: I don't have an extra layer with me in the summer and I'm freezing in the store/theater/restaurant. I can only hope that this is an American peculiarity.

Singapore has this issue too. Hotel conference rooms (and some offices, I'm told) will be set to 19⁰C or something equally not achievable so AC works full blast, while outside is humid high 30s.

For large spaces there's more considerations than more person-sized spaces. If you make your theater or restaurant comfortable when it's empty and people are walking in, you'll need much bigger AC gear to catch back up once everyone's in there generating heat. It's one of those cases of a problem being quite a bit harder than you might intuitively think because for the most part, engineers have just solved it for you in most spaces, but there are some places where it just gets too hard to fully solve. Variations between locations are probably accounted for in differences in code and how much money there is to spend on the heating and cooling gear, plus how much variation there is in the outdoor weather.

IIRC a person can be approximated as 100 watts of heating. If you add up everyone in the full restaurant or theater you get quite the number for how much heat the people themeselves are putting out.

Heat people, not places: https://www.lowtechmagazine.com/2015/02/heating-people-not-s...

That's nice for heat, but thermal mass means that air conditioning is most efficient when it can get the whole room to equilibrium and then shut off. Like a car coasting going down a hill.

I always see it like this, if it's cold you can put on more clothes (you probably already have them, and they don't waste energy to wear). When it's hot, there's a certain societal lower threshold for what you're allowed to wear in an office (depending on the office shorts are ok, but not less). So you can't individually cool down.

I just bought my apartment last year and I made the decision to use infrared panels for heating. Best decision ever. No moving parts(no noise and no constant breeze), no dry air indoors, the heat is actually stored in the walls and furniture(denser objects), so I can vent the air regularly without loosing much energy. And it's supposed to help generate vitamin D which during the winter is usually a problem. The downside is that it takes longer than air conditioning to warm up the same room and it requires great wall and floor insulation(which I have). There is also the problem of overshooting the temperature(because the panels don't cool immediately, it takes about 15-20 min), which is solved in some thermostats using hysteresis algorithms for the temperature delta(it uses shorter cycles between on and off and more precise measurements, however this could wear the electrical panels quicker). I'm not that sensitive to the temperature so I don't use those and I have my temperature sensitivity up to 0.5C.

Sorry to disappoint you, but vitamin D3 synthesis is triggered by UVB, not IR

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897598/

Yes, you are correct. I've misremembered the effects. However there are other positive effects from infrared light.In any case, this is just a bonus to the actual purpose of the panels.

What did you buy exactly? This sounds interesting but I have never heard of this.

There are many different manufactures and models. Mine are constructed in Austria. Here are some examples: https://www.redwell.com/en/products/ https://www.sundirect-heater.com/frameless-infrared-panel-he... https://www.heat4all.com/en/products

The cool thing is you can make it part of the interior. I have 3 panels hanging from the ceiling, 1 painting and one mirror. They can be integrated into hanging or floating ceilings and usually have standard dimensions. You have to be aware, that most panels do not have thermostat. They have only one operating mode - On. In order to regulate them, you have to put a thermostat on the electrical line before it(essentially a smart switch). There are thermostats for wall integration. I use those, the cables are hidden in the wall and the actual thermostat is mobile so it can measure temperature at any location in the room. There are also thermostats which are plugged directly on electrical sockets for more integration out of the box. The price is comparable to any other heating solution and the consumption is a little less than air conditioner. Mine came with 5 year warranty. I just hope that they last longer, but with the exception of the painting, all the rest are easily replaceable.

I was looking into infrared panels as well, but was slightly worried reading that they may cause your eyes to become cloudy. Is this something you heard of?

The mantra I've heard is "move heat (energy) don't make it". Don't burn or even use renewable enery to generate heat but move heat already present. Move it away to cool and move it towards somewhere that needs heat.

Well, jumpers and thick gloves. Due to circulatory issues my hands often turn numb and blue in offices where the AC is cranked up, even if the rest of me is toasty warm.

Maybe you should drink tea. It would warm you up and supposedly tea has mild blood "thinning" properties. You're not supposed to drink tea if you're going to have surgery.

For air conditioning the best part of it is the dehumidifiation. It doesn't need to be arctic cold just the dryer air and a bit of cool is OK.

OP could be referring to Raynaud syndrome (https://en.wikipedia.org/wiki/Raynaud_syndrome). It's not sure tea helps in such cases.

Thanks for the link! I had not heard of the syndrome before. but it could be what my wife has been suffering from for the past year or two. We already are waiting to see a specialist to have a look at her, so I won't make any conclusions, but that seems very likely it.

I have Raynaud's disease and cold weather alone isn't a trigger for me unless I am not wearing gloves and if I am holding onto something. A shovel when shovelling snow, or pulling a heavy cart. It has to be a continuous session not just one thing for a few minutes.

I've also been sitting quietly at home and suddenly half my thumb goes purple and the other half is fine.

You know it's Raynaud's syndrome because it feels like someone hit your hand with a hammer. It's not just cold hands it's the pain too.

As much as I am a huge fan of tea, in this case I think the vasoconstrictive property of caffeine would have the opposite of a therepeutic effect.

Always the same AC fight at the offices, one of the things I don't miss with this work-from-home. My preferred room temperature would be 27C which is obviously a no-go in a shared office, but cooling to 20C in summer is just as crazy too.

> There are costs, as heat or/AC will have to run more to keep the temperature in the right range.

Heat recovery ventilators can largely solve this problem, while also reducing particulate pollution indoors.

Interesting, with climate change CO2 will be increasing to over 450 ppm at some point.

Will we have an issue with airborne diseases?

No the co2 is a proxy for air exchange with the outside. It is the air exchange that prevents disease, not low CO2.

Submarines tend to operate at CO2 levels around 3500 ppm, and there doesn’t seem to be strong evidence of any cognitive effects.

Infectious disease would be more of a concern, but the submarine itself is a pretty effective quarantine.

Yes. Or, spend less time inside. That we spend so much time inside is a unique feature of our time, and a very bad one.

Regardless of air or sunshine (which are both extremely important to our physical health), not being outside makes us unhappy. People who work outside often sing while working; when was the last time you heard someone sing in an office.

There's also a vast difference in the types of work being done outside vs in an office; when was the last time you heard someone sing while documenting code?

I've been wondering about this for a while, do you have a reference?

Do you know how humidity affects transmission?

Pre-pandemic I used to go indoor bouldering where there tends to be a lot of chalk in the air and I was curious how that affects transmission. Couldn't decide if the dryer air meant less transmission, or the larger particles meant more maybe. Couldn't find anything about it.

https://onlinelibrary.wiley.com/doi/full/10.1111/ina.12639

Any evidence for this?

The point here isn't that CO2 matters. The CO2 is just a marker for adequate ventilation (and there is plenty of evidence that ventilation is very important in reducing transmission).

https://onlinelibrary.wiley.com/doi/full/10.1111/ina.12639

People in not too distant future will likely view with envy the readily available fresh air we currently have. Given that in a century or two the CO2 concentration in outside air may reach the 'stuffy classroom' level[1].

Imagine that, having to live and work in oxygenated habitats on our home planet.

https://www.acer-acre.ca/resources/climate-change-in-context...

This is a plot element of the movie "Spaceballs".

I was thinking about that the other day when reading about shortages of medical oxygen in India due to the COVID-19 crisis. That movie picked the plot device because it was so ridiculous and now it could be a real problem in some cases.

In case anyone is looking for a citation, here’s a recent peer reviewed study of a Taiwan university and how increasing ventilation greatly reduced tuberculosis infections.

https://onlinelibrary.wiley.com/doi/full/10.1111/ina.12639

Any source for this claim? (I kind of trust you, just wondering if you have a specific source to offer)

Not having to sign for deliveries.

You look at the science part I look more on the process. If the compromise on the medical alertness, that we do NOT stand to power (let me do suicidal and say both china and Trump), that we did before in SAR, in ...

That is a great lost.

And when 2nd one come as it would may be in 2 decades how back our human institution is. That is the bad part.

Science is one of the few area we can improve on. It is what around it that is worrying.

How about who will control gene editing and the recent experiments on mixing human genes or chinese doctor trying to do designer baby (perhaps with an excuse of fighting aids).

There are too many different strains of rhinoviruses that cause common cold. It is possible to create a vaccine against each strain, but no vaccine that would target at least a significant amount of strains is possible at the moment.

> no vaccine that would target at least a significant amount of strains is possible at the moment.

Why not? What are the limits of multivalent vaccines?

It could very well go the other way where the pressure put on the common cold forces it to mutate in such a way that makes it more contagious/deadly

Wouldn't it be the reverse? If we're killing off the viruses that cause dangerous symptoms, wouldn't there be selective pressure towards less dangerous symptoms?

> (Of course, it's also possible that by thinking we've 'cured' the common cold, we will open ourselves up to a once-a-century pandemic, where millions are wiped out by what used to just be a common cold.)

H.G. Wells knew his stuff

I'm wondering more about the effects the increased cleanliness will have on people's immune systems --- all the masking, social distancing, constant hand sanitiser use, etc. is, in addition to reducing exposure to COVID, also reducing the exposure to the countless other pathogens that people are normally exposed to. Does the lack of exercising ones' immune system have a cost too?

A lot of people wonder this first part and the answer is definitively no because immune systems generally don’t work that way. It’s (mostly) not something general purpose like a bicep. Getting sick with one diseases mostly does very little for you with most other diseases.

You can lift weights at the gym and build your arm muscles, then use those muscles to lift or push other things more effectively, because muscles are general purpose tools.

Most of your immune system is more like a key. It’s specific to one thing. There are some exceptions but overall the fewer viruses you encounter the better.

As for the exercise: yes. There’s already preliminary evidence that exercise is highly coordinated with covid outcomes.

> As for the exercise: yes. There’s already preliminary evidence that exercise is highly coordinated with covid outcomes.

GP asked “lack of exercising one’s immune system” not “lack of exercising” in general.

Hi, I'm surprised by your "definitively no" as I understood this as still an open question - particularly with respect to autoimmune risks.

Do you have any resources to help me understand your position better?

Still lots of debate as to how the immune system works. If we understood it there wouldn’t be millions of people suffering from allergies (some who get it after moving to ‘clean’ western countries)

There is the Hygiene Hypothesis, which is the reverse: Decreased exposure to some pathogens, especially when young, can make the immune system overly sensitive and thereby increase the risk of atopic and autoimmune disorders.

On the (maybe?) reverse: I grew up on a farm and later moved to a big city to study computer science. It was only then that my allergy kicked in. I wonder if that would ever have happened if I had gone the farming route in life :P In any case, life in the big cities seem to mess with our immune systems.

This may be due to what trees are planted in cities:

https://blogs.scientificamerican.com/guest-blog/botanical-se...

Are people still using lots of hand sanitizer? Why?

Some are - at least most doing COVID Vaccination administration are people that I can personally say are using "lots" of hand sanitizer each day. (yes, my hands still hurt)

No, not really. That died out rather quickly, as did singling “Happy Birthday” while washing one’s hands.

> Are people still using lots of hand sanitizer? Why?

We're still using lots of hand sanitizer here, because the combination of masks, social distancing, and hand sanitizer seems to work. Though, we could be mistaken about the relative effectiveness/necessity of the three measures. My office building has hand sanitizer dispensers in the entryway.

Yes, it's primarily a respiratory virus, but the cost of hand sanitization is pretty low and the virus remains infectious on most surfaces for several hours. Here in Hong Kong, we're one of the most dense cities on Earth, with a lot of public transit use, so surface contamination may be more of an issue here than in other places.

Businesses stock sanitizer because it's cheap and compatible with the status quo ante, not because there's any reason to believe it's effective.

Sanitizer is for more than just covid. We were washing hands long before covid, and I hope it continues

My kids have been coming back from school with the backs of their hands bleeding because they're so dry from being forced to constantly use sanitiser all day. This is because government guidelines have not been updated since it became clear that it's not transmitted by contact. We've had to tell them to use the smallest amount possible, and only on their palms.

As far as I'm aware the only reason to use hand sanitizer is because soap (which is more effective - again AFAIK but this has been told since the start) is even more damaging do the skin when done often.

Let's not forget the incredible "convenience" factor of waterless hand sanitizer. Who needs a pesky basin, soap & running water when you can just spray this magical liquid on your hands and be done in a jiffy.

The purpose of the sanitizer is not to prevent contagion by contact, it's for you to make sure that your hands are clean before touching your face (mouth, nose, eyes). That's how you get infected, the virus get onto your hands for whatever reason and you touch your face. So technically it's true it's not transmitted by contact directly but it does indirectly.

Yes, I understand that, but that's still a vanishingly rare route of transmission. The way you get infected is by inhaling aerosols.

Really? So... where do the guardians of these children draw the line? There's no line... just say it. The "gov mandate" conditioning is so well tested through history.

Kids, highest risk group for this flu virus... right?

Psychologically, they are, and I think you know that.

> [..] since it became clear that it's not transmitted by contact.

That'll need a reference. It's only a few weeks since a worker was infected in a one-person workshop[1], from the guy working there two days earlier. Testing showed that it was the exact same (rare) virus strain and the only explanation was that the second guy got infected from using the same tools as the first guy (not infected _through_ the hands of course, but presumably by touching his face afterwards. As one does).

(Keeping surfaces clean is the most important part, otherwise you'll have to clean your hands every time you touch something. As for myself I've become very self-conscious about what I touch.)

[1]https://translate.google.com/translate?sl=no&tl=en&u=https:/...

Very interesting, thanks. Though it remains exceedingly rare so far as we can tell.

Assuming they did good contact tracing here and found that it really was the only way this guy was exposed, we're talking about a vanishingly rare route to infection. The article calls it one in a million infections. I think it might be rarer than that.

Sure. When I said "not transmitted by contact" I should have said "rarely transmitted by contact". It has become clear that the overwhelming majority of transmisson is through aerosols indoors.

https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-r...

https://www.nature.com/articles/d41586-021-00251-4

I like the way it makes my hands smell.

>I have wondered if the COVID-19 pandemic might lead to some results, like extermination of the common cold

But coronavirus is just one of the several viruses which cause common-cold symptoms unless COVID-19 level attention goes to every single one of them I doubt we will ever see an end to it. It's estimated that 20% of coronavirus causes cold.

Perhaps some accidental discovery with mRNA level technological leap would prove me wrong.

I've heard the claim that one of the "common cold" corona viruses, HCoV-OC43, was actually a nasty former pandemic virus (the so-called "Russian Flu" of 1889-1890, which is estimated to have killed about 1 million people).

yeah, I read articles about this as well but since there are no samples we don't have evidence in favour or against that hypothesis.

Ok, but curing 1/4 of the common cold is still a big step. (Coronaviruses cause about 1/4 of "common cold" cases now.)

I agree that even 20% I mentioned is worth curing.

Even in COVID-19 running nose was one of the rare symptoms listed, I wonder whether the second/third wave with new variants has changed that because from the anecdotal statements I hear here(INDIA)[1] the symptoms might have altered.

I feel more data related to symptoms needs to be collected and published.

[1] https://timesofindia.indiatimes.com/life-style/health-fitnes...

It looks like it's the malaria vaccine [0]

[0]https://www.bbc.com/news/health-56858158

Thanks to the pandemic, Ivermectin, a widely-used anti-parasite that won the Nobel prize for virtually eliminating river blindness (https://www.nobelprize.org/prizes/medicine/2015/press-releas...), a medicine on the the WHO essential medicine list, which has shown broad-spectrum antiviral properties in the lab (zika, dengue, west nile virus, covid and more https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564151/), has also proven very effective against preventing and treating sars-cov-2 virus in vivo: https://ivmmeta.com/

The probability that ivermectin generated results as positive as the 52 studies to date is estimated to be 1 in 85 trillion (p = 0.000000000000012).

A doctor who thought they had covid, took ivermectin and turned out their covid results were negative, but it still aided their recovery for the flu.

Dr. Pierre Kory gave an excellent discussion on the latest scientific findings of ivermectin as as a treatment for covid and general antiviral treatment on John Campbell's youtube channel: https://www.youtube.com/watch?v=19DPijOoVKE

Personally, I think a drug with 37 years safety data makes a more promising candidate than a novel therapeutic that is rushed to the market.

Looks like Ivermectin has generated a lot of buzz that many are self medicating. The first link that google throws up when searching for Ivermectin is the FDA page "Why You Should Not Use Ivermectin to Treat or Prevent COVID-19" https://www.fda.gov/consumers/consumer-updates/why-you-shoul...

I have no opinion on Ivermectin, but I find it odd that the FDA keeps implicitly recommending remdesivir [0] while the WHO (together with several European countries) recommends against it [1]. I believe the FDA is compromising its credibility, which is sad.

FDA: "The FDA has approved the antiviral drug Veklury (remdesivir) for adults and certain pediatric patients with COVID-19 who are sick enough to need hospitalization."

WHO: "WHO has issued a conditional recommendation against the use of remdesivir in hospitalized patients, regardless of disease severity, as there is currently no evidence that remdesivir improves survival and other outcomes in these patients."

[0] https://www.fda.gov/consumers/consumer-updates/know-your-tre...

[1] https://www.who.int/news-room/feature-stories/detail/who-rec...

[2] https://www.has-sante.fr/jcms/p_3201940/fr/evaluation-des-tr...

If it works, not very well. There were some very small underpowered studies that showed promise. Then large RCTs were done and it didn’t work. Brazil would certainly not be in the situation it’s in right now if ivermectin cured covid.

https://www.gavi.org/vaccineswork/ivermectin-why-potential-c...

> also proven very effective against preventing and treating sars-cov-2 virus in vivo

No. India and Brazil are giving Ivermectin liberally. See how good they're doing

> is estimated to be 1 in 85 trillion (p = 0.000000000000012).

Their estimation is BS. Or better, it's the famous "CICO" (crap in, crap out) statistics

"Oh but it won the Nobel prize". Yes and John Voigt won an Oscar, doesn't mean his performance in Anaconda was up to snuff

Incorrect, only certain areas in Brazil and India are using Ivermectin which makes for excellent epidemiological studies showing ivermectin's effectiveness in areas that use it versus areas that don't: https://covid19criticalcare.com/ivermectin-in-covid-19/epide... (India and Brazil are towards, the bottom of the page, several other countries data show identical results where introducing ivermectin treatments causes death rates to drop)

> only certain areas in Brazil

Incorrect, if you go to any pharmacy in any area of Brazil you'll find it being liberally sold even without a prescription. (one of multiple references https://g1.globo.com/sp/sao-paulo/noticia/2021/03/29/uso-de-... )

Also go look up the numbers of Drug-induced hepatitis caused by Ivermectin in Brazil

My understanding is that even if the drug is available in Brazil OTC it has become politicized, so it's not considered standard of care. Do you have any links where health authorities in Brazil have made it standard of care?

Ivermectin is incredibly safe. "Acetaminophen overdose is the leading cause for calls to Poison Control Centers (>100,000/year) and accounts for more than 56,000 emergency room visits, 2,600 hospitalizations, and an estimated 458 deaths due to acute liver failure each year." https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.20...

"Hepatic adverse events Ivermectin was suspected to be a hepatotoxicant. In fact, this claim reproduced in several publications was based on few individual case reports [Sparsa, 2006; Veit et al., 2006; Hirota et al., 2011] where the causal relationship with ivermectin treatment was not convincingly established. The last update of LiverTox [2018], a database of drug-induced hepatotoxicity, did not classify ivermectin as a known hepatotoxicant, a conclusion recently confirmed by the US National Institutes of Health [NIH, 2021]."

Taken from a recent 48 page review of the the entire literature on Ivermectin safety by a medical toxicologist: https://www.medincell.com/wp-content/uploads/2021/03/Clinica...

(edit: not 50,000 liver failures, 56,000 er room visits :)

> it's not considered standard of care. Do you have any links where health authorities in Brazil have made it standard of care?

"Nobody cares" about standard of care. The medical college (CRM) has pretty much said that the doctors are free to prescribe whatever they want

> Ivermectin is incredibly safe.

Yes, at the recommended doses for parasite control (which is a single or dual dose), not for usage for several consecutive days or weeks (and I agree with the Paracetamol criticism)

Anti-depressants are approved after a few weeks of study, and people use them for years without safety concerns. People have taking 10 times the dose of regular ivermectin without harm (https://pubmed.ncbi.nlm.nih.gov/12362927/). I guess we are in slightly uncharted waters with ivermectin, but there is no evidence from the people who chronically prophylax for covid that regular dosing has caused them issues.

And ivermectin is safest of the current covid treatments, so I find it hard to accept that we shouldn't use it because of safety concerns (for comparison, since 1992 the pharmocavigilance database shows less than 1 death per year from ivermectin, where Remdesivir has 500+ deaths, vaccines has over 2000 deaths with only months of usage).

There's no evidence that it works. The studies used concentrations that were roughly 1000x a regular human dosage.

https://sciencebasedmedicine.org/ivermectin-is-the-new-hydro...

The theory that ivermectin’s anti-viral activity is dependent on unachievable tissue concentrations is incorrect as follows:

In the cell culture study by Caly et al from Monash University in Australia, although very high concentrations of ivermectin were used, this was not a human model. Humans have immune and circulatory systems working in concert with ivermectin, thus concentration required in humans have little relation to concentrations used in a laboratory cell culture. Further, prolonged durations of exposure to a drug likely would require a fraction of the dosing in a short-term cell model exposure. There are multiple mechanisms by which ivermectin is thought to exert its anti-viral effects, with the least likely mechanism that of the blocking of importins as theorized in the Monash study above. These other mechanisms are not thought to require either supraphysiologic doses or concentrations and include competitive binding of ivermectin with the host receptor-binding region of SARS-CoV-2 spike protein, limiting binding to the ACE-2 receptor; binding to the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), thereby inhibiting viral replication (Swargiary, 2020); binding/interference with multiple essential structural and non-structural proteins required by the virus in order to replicate. The theory that ivermectin would need supraphysiologic tissue concentration to be effective is most strongly disproven by the now 24 controlled clinical trials which used standard doses of ivermectin yet reported large clinical impacts in reducing rates of transmission, deterioration, and mortality.

Had discussions on this with our close friends who work as doctors at the covid front line (emergency & intense care unit) in Switzerland's biggest hospital (since wife is a doctor herself we know a lot of them).

The feedback? Meh, provably doesn't work in regular doses, +-works in lab culture when dosage is 1000x the regular one with god knows what side effects, and thus no doctor here uses it. Its not some emotional dismissal, but deep study of available research by top medical virology experts in a country which has more money to spend than any other on this, and plenty of this medicine if its proved working. They discuss & evaluate daily all available information, and Ivermectin simply doesn't pass as anything even remotely working.

Now I am far from virology expert myself, but I don't mind listening to massive group of experts. I've seen some people propagating this drug, presumably in good faith. But from the outside it looks exactly like another conspiracy theory when you can't discuss with people about simple facts. All this because of some web page, youtube channel etc going mental in one single direction, about one 'expert' who discovered truth that governments and pharma corporations don't want you to know

Tens of thousands of patients have been tested in double-digit, peer-reviewed RCT's, showing high efficacy:

https://c19ivermectin.com/

Sounds like the doctors you spoke with didn't have any experience with ivermectin and are referencing old information (1000x standard dosage is needed). There are many doctors who do use it and see good results. Slovakia recently started using Ivermectin widely in March (https://twitter.com/BIRDGroupUK/status/1385990416730923013) and saw steep reduction in deaths. If you are interested in having a good faith discussion about ivermectin facts, that would be great. What questions do you have?

Are you Brazilian?

It's weird how often on threads about covid, an entirely new HN account turns up to extol the virtues of Ivermectin. I'd say the chances of that being a coincidence are estimated to be 1 in 85 trillion.

Here in Brazil there is a manufacturer that finances a group that promotes its use.

"The sale of vermifuge ivermectin jumped from R$44.4 million in 2019 to R$409 million last year, an increase of 829%."

(In portuguese) https://negativando.medium.com/m%C3%A9dicos-pela-vida-s%C3%A...

If you are skeptical of financial motivated misinformation - are you concerned that the parent article - touting an unapproved FDA cure for covid - is placed on a website that advertises it sells sponsored content articles: https://www.postmediasolutions.com/solutions/content/

Or that the FDA promotes Remdesivir which make's Gilead billions of dollars, where the largest non-manufacturer sponsored trial by the WHO showed 0 benefit for saving lives?

Why is hacker news so excited about something that may take months to get to market, currently has less efficacy data than ivermectin, and will never have the safety profile of ivermectin?

Maybe potentially saving lives by providing negligently under-reported and big-coughtech suppressed information is enough to motivate someone to set up an account?

This is the first time I see this and so at least to me, an actual counter to their points would have been more of a convincing argument, compared to accusations of shilling which might as well be FUD.

They aren't FUD. Click on the accounts mentioning Ivermectin, and they are just new, and only have one comment.

Sure, it might be that a dozen long time lurkers had to create an account to made people aware of it. Its plausible.

I think its more plausible that HN is suffering a disinformation attack by a cheap as botnet.

A limit of "wait 1 day after registering to comment" would make whatever cheap botnet is doing this much less effective. Since after 1 day most stories are not in the frontpage anymore.

I only see one single new account that has made multiple comments in this thread.

One guy signing up or creating a throwaway isn’t exactly unlikely.

It's not a botnet. Am a long-time hacker news reader who thinks ivermectin is a better covid cure based on science than what Pfizer is rushing to produce (Pfizer's drug hasn't even finished Phase 1 FDA trials, Ivermectin is FDA approved with ~40 years safety data). I use multiple machines and didn't remember the password for this account so created a new one. My interest is not in spamming, but having a genuine discussion, why ivermectin isn't more widely used. There are multiple prominent doctors who believe it could end the covid pandemic. Why get so excited about new medications when generics are cheaper, and have better safety data.

Other treatments have good data like Fluvoxamine, here's a good article from Steve Kirsh: https://www.quora.com/Is-there-any-cure-for-COVID-19/answer/...

Am interested in a genuine discussion of facts. There's a lot of censorship around Ivermectin. Youtube specifically says it can delete videos mentioning ivermectin as a treatment for covid. Since when is science advanced through censorship instead of debate?

> Since when is science advanced through censorship instead of debate?

Science is never advanced through debate; it's advanced through research. Research which gets repeated by different teams, in different places, in different circumstances, and conducted in different ways, while still producing the same results.

Random people on internet discussion boards who want to advance science via a "debate" is how misinformation is advanced.

Guidelines ask you to refute content rather than accuse of shilling. If you have evidence of shilling you should email the mods instead. Guidelines also ask you to not post the same comment twice.

Disclosure: no dog in the fight and never heard of this drug before.

Ivermectin is an antiparasitic in wide human and veterinary use since the early 1980s. It is also fairly broadly studied, in no small part because it's one of the most effective drugs in its class. That it should double as a highly effective broad-spectrum antiviral is not impossible, quite, but anyone advancing the claim badly needs to explain why, over all the dozens of studies and millions of doses over multiple decades, no one has noticed this supposedly very obvious antiviral efficacy before now. The next person I see try to explain that will be the first.

The discovery came years ago: "Dr Wagstaff made a previous breakthrough finding on Ivermectin in 2012 when she identified the drug and its antiviral activity with Monash Biomedicine Discovery Institute’s Professor David Jans, also an author on this paper. Professor Jans and his team have been researching Ivermectin for more than 10 years with different viruses." https://www.monash.edu/discovery-institute/news-and-events/n...

Lots of things work in vitro, this apparently included. Arsenic probably would too. Cell culture is a very different environment from a living organism, so all this says about whether the same drug works the same way in vivo is that it's worth finding out. Despite the usual mild tendentiousness one finds in press releases from academia, the linked article says as much, repeatedly and in detail.

Correct dosage and a dependency on administering in conjunction with Zinc. This is well-established in controlled studies conducted over the past year. Look at the data from the many controlled human trials, it's conclusive. Suppressing it kills people.

Where is that data? You seem very familiar with it. Why not link it? Why do all the links you do post point to random novel .coms with huge batches of totally unrelated studies that just happen to have "Covid-19" or "SARS-CoV-2" in the name, rather than to PubMed, BMJ, or any other more direct source? Why not detail the analysis that led to the conclusion you present? Why do you prefer to talk about your claims of censorship and suppression than talk about the science?

Your statement about "huge batches of totally unrelated studies" is completely false.

All studies on c19ivermectin.com are directly related to Ivermectin efficacy versus SAR-Cov-2, a small number relate to Ivermectins viral efficacy in general.

Hot off the press (all peer-reviewed):

Ivermectin SARS-Cov-2 binding:

https://link.springer.com/article/10.1007/s13721-021-00299-2

https://www.frontiersin.org/articles/10.3389/fmicb.2020.5929...

https://www.nature.com/articles/s42003-020-01577-x

Ivermectin in humans, versus COVID-19:

768 outpatients, prospective trial vs control, significant improvement:

https://www.sciencedirect.com/science/article/pii/S120197122...

Infections - 0 of 788 treated, versus 237 of 407 in control group:

https://medicalpressopenaccess.com/upload/1605709669_1007.pd...

Retrospective, 3099 infected patients treated, 1 death:

https://www.longdom.org/open-access/the-use-of-compassionate...

Examples of counter-studies against Ivermecitn or HCQ (similar profile and response) in journals you love:

https://jamaletter.com/

The infamous Lancet front-page retrospective observational study on HCQ which turned out to be based on zero verifiable data, despite passing Lancet's "peer-review". (Sorry no link, it's been retracted.)

Certainly on Twitter, hyping ivermectin as the cure is also good Bayesian evidence that the speaker also believes a bunch of unevidenced or plain wrong things about Covid19.

That's been my experience in the real world as well, which has the result of making me very skeptical of ivermectin.

> Over the following 10 years, these inventions saved 4 million lives and saved 15 million days of lost work/school.

I have a more pessimistic view on that. It means that it took 4 millions death to realize that we could use resources to save millions of preventable deaths if only we invested a bit more in R&D.

Eradicating diseases is not technologically hard, but it requires budget. I wish as a society we would find it more commendable to invest in the obviously good endeavor of saving lives.

I am all for vaccines for really dangerous diseases, but we also need to get ill to keep our immune system active and healthy. For example, there are links between being in too clean an environment as a baby and then developing leukaemia. There is similar evidence for other autoimmune diseases.

https://www.sciencedaily.com/releases/2018/05/180521131746.h...

Vaccines work because they keep the immune system active and primed to recognise the disease being vaccinated against.

Not all vaccines work the same way and it is not obvious what the long term impact of such a "flu pill" would be on our immune system. For example, I would like to know what would be the long term impact on children who do not get exposed to common colds while they are young. Would they go on to develop more autoimmune diseases. They might not, but it is a pretty big unknown.

> we also need to get ill to keep our immune system active and healthy.

This... is exactly what (many) vaccines do.

> Over the following 10 years […] and saved 15 million days of lost work/school

Still not worth it by few magnitudes. Just in France (67 millions inhabitants) there was over 100 days of lockdown in total. That 6.7*10^9 days wasted in less than a year. And the current lockdown continues…

This is a slippery slope I think (even letting aside the fact that frequently such a cost-benefit invariably comes down to 'hey, the cost borne is skewed more towards the poor, while the benefits are skewed more towards the rich / otherwise privileged'). If we then also don't tackle climate change as strongly as we otherwise might, or work less to improve living conditions all around the world (since we now have a magic pill), then the long-term net effect is still bad.

That we discount the geographically and temporally distant too much, and the local almost not at all is a) what helps us locally survive & b) what causes our long-term downfall.

Oh, definitely. Not (just) for the common cold, but for all the other places where Covid shook us from the local maximum. The obvious are WFH, ecommerce, deliveries, courier businesses, normalizing masks in the western hemisphere. More subtle is the general shaking and closing of unprofitable businesses and making room for new ones. Yet more subtle is rubbing everybody's nose in the fact that long term risks and black swans are something that should be paid attention to.

But by far, the most useful thing we got of this pandemic is once again moving medicine up in the priority list. Lately it had gotten stuck at "hiv is not curable, let's have another cancer fundraising". And one year later we're at "vaccine for cancer, pill for common cold", plus god knows how many other things. And hopefully, just hopefully, it's shown enough people that FDA-style organizations are a huge brake for serious progress. Challenge trials -> vaccinations started 6 months earlier -> probably 0.1% deaths overall (yes, it's 6 months in an exponential).

I have a child that has been admitted to hospital over 20 times with severe illness (bad pneumonia, horrible saturation) with common cold (congenital lung issue).

The common cold is a 1-2 month ordeal with an ambulance ride in the middle. If someone made a pill that just made common colds less severe in the lungs, it would be absolutely revolutionary. Our healthcare system could pay $20k/year for my child to have that and still make money. Heck, I'd pay that out of pocket if they didn't.

skipping work/school is important for individual development, a lot of times

Not when you're spending time not at school on the sofa or in bed feeling miserable and unable to do anything.

why not? feeling miserable and unable to do anything might be part of a normal development.

My attitude has been that a global pandemic was an unavoidable event bound to happen on an overpopulated world that is connected by robust air travel networks.

And it won’t be our last, so we had better start learning how to deal with them. I give us a C- right now. The vaccines were great, but the public governance left something to be desired.

The day the US stops air travel, many (myself included) will understand the severity of a proposed pandemic.

Since domestic air travel continued unabated and without direct testing to board a flight, it’s not hard to see how many people got the idea that this pandemic wasn’t all that serious.

Dr Fauci never once suggested it - to the best of my knowledge.

It was public health orthodoxy that travel restrictions are some combination of ineffective and counter productive.

Which there are infection scenarios where that might be true. This obviously wasn't one of them.

A standard line is that we couldn't restrict travel in the US because we aren't an island. But we didn't do much of anything, our travel was much more extensive than necessary.

It is also the very first time we are doing it.

Maybe not THAT bad.

For the sake of argument just imagine it was a bio-warfare attack on the US (it isn't) and compare casualties to, say, Pearl Harbor, or 9/11. Before the pandemic, would you have expected US society to sacrifice half a million American lives?

Considering the 1918 Spanish Flu pandemic occurred in a less populated world not connected by robust air travel networks and still managed to spread to every country in roughly the same timeframe would indicate that neither total population nor air travel are variables in the spread.

If there only was this vast field of computer scientists, mathematicians, physicists, biologists and disease experts that do nothing else but model the spread of infectious diseases.

Not surprisingly it turns out that travel networks play a major role in the early phases of a pandemic [1].

[1] https://science.sciencemag.org/content/342/6164/1337

Awesome! They should totally go all out investigating this.

The rest of us should totally not get too excited. Many drugs go into phase 1. Few come out. There are more phases after that. Tamiflu got through all of that and still hasn't been a game-changer for something that kills tens of thousands in the U.S.A. alone every year.

But, hey, you have to take a lot of shots on goal before you get one, so I'm glad they're going after it with a sense of urgency.

Which phases did the vaccine go through?

Which vaccine?

They all went through at least phase III, even Russia's Sputnik vaccine (even though they announced it as a success before they had their phase III completed).

The Merck/Pasteur vaccine was abandoned after stage 1. The Sanofi vaccine had poor stage 1 results, but they seem to be indicating that they plan to continue development with a much later projected laucnh date. I don't know if that is because they mean they're trying a different candidate entirely or if they're making changes to the failed one.

Well, yes, my assumption was that he was asking about the vaccines that are currently in use. The fraction of drugs/treatments, broadly speaking, that make it past stage 3, is <1%.

Not sure why the downvotes, it's a legitimate question. So there's a phase to see if there are huge side-effects in humans, then a phase to see what dosage to use for effectiveness, then a larger (tens of thousands) phase to get enough data to justify using it on millions of people. I think there are normally more phases after that when you're not in a pandemic.

This SARS-CoV-2 protease inhibitor is the latest scientific overlap of COVID and HIV -- I am so hopeful that cross pollination will (continue to) lead to breakthroughs for both diseases.

The clinical trial in question: https://clinicaltrials.gov/ct2/show/NCT04756531

The related intravenous antiviral: https://clinicaltrials.gov/ct2/show/NCT04535167

Actual title: "Pfizer is testing a pill that, if successful, could become first-ever home cure for COVID-19" - Edited down as best as I could to fit the length.

This article is a syndicated copy. This is the source: https://www.telegraph.co.uk/global-health/science-and-diseas...

Totally OT: that video pop-up, you click the close button and it disappears but as soon as you scroll it reappears. Evil.

Welcome to the hell that is Postmedia websites.

It's not suffice that all of Canada's local newspapers were acquired by one giant conglomerate and is slowly killing them off, but they've also make some of the worst website experiences.

Ah, that also explains why when I looked at the top of the page to find which website/newspaper it is my attention was drawn to the two imposing CTAs (manage subscriptions and signup).

Also, the video covers up some parts of the text, which is the reason I want to close it.

Things like that make me so irrationally angry. News websites are the worst

I hated that too, but I assumed it was incompetence rather than malice. If you want an uncloseable video, it's a lot easier to just not put a close button on it.

I refused to read the rest of the article because it irritated me so much.

Here is an article on the same thing, but at Forbes: https://www.forbes.com/sites/melissaholzberg/2021/03/23/pfiz...

Do drug R&D departments do off the books clandestine testing of compounds to screen them before moving onto the official testing steps?

With the expense of testing being so huge, it seems like there would be huge economic incentive to be able to fail fast.

I wonder what percentage of pharma researchers are bold (and unmonitored) enough to test their creations on themselves - based on the chemists I've met, it almost certainly must be nonzero...

I like to think that medicinal chemists are self-aware enough to not ingest anything they design, lol. There'd certainly be a lot more corpses than drugs in the market with self-testing.

In either case, I've definitely considered injecting myself with optogenetics expressing virus to skip a few decades of R&D.

Hey, it worked for Albert Hofmann!

Then there's Alexander Shulgin.

https://en.wikipedia.org/wiki/PiHKAL

This guy CRISPR'd himself.. https://www.cbc.ca/radio/quirks/diy-dna-hacks-wounds-take-lo...

AFAIK a lot of drugs can be fairly assumed to be mostly safe (aka won't kill you), although they may have long-term/non-lethal effects. So testing your own drugs wouldn't be creating that much corpses as long as you know what you're doing.

The early official testing steps are in cell lines and animals.

And then to do a one off test of a compound that inhibits a virus you have to expose yourself to the virus.

I don't particularly doubt your speculation that there are cowboys, but I'm not sure what they would expect to learn by administering these complex compounds to themselves.

I have definitely heard of rumors of such things happening in the 90s in some centers in India but never substantiated. I’d be surprised if nothing like that happened though!

If you ever did this at a pharma company you’d find yourself without a job pretty quickly.

When it comes to proper testing, drug companies tend to stick to the rules lest they incur the wrath of the FDA. The FDA won’t think it’s bold when employees start testing on themselves.

Plus, R&D folks gets to hear all the stories of side effects in lab animals like necrosis of the testicles and such. Tends to give cowboys 2nd thought to self-testing.

> The trial is split into three phases and will run for 145 days, with another 28 days added for “screening and dosing”. For all participants, there will be several overnight stays.

Let's not get too excited...

I am getting excited. They are doing really strong due diligence which will only increase public trust and confidence. If it fails, then oh well, atleast we tried.

Oh for sure they're doing exactly what they should do, but America will likely be approaching vaccine-induced herd immunity by the time the FDA begins to consider the results of these trials.

It may have a bigger impact in other nations, but hopefully they'll have ramped up their vaccine programmes in the next 6 months.

good, I would like to travel soon. my back yard has gotten very boring.

Gargling and snorting mouthwash until this is ready. https://academic.oup.com/jid/article/222/8/1289/5878067

Perhaps consider a Carbolic Smoke Ball as well!

Not necessarily.

That is just testing if COVID19 breaks down when exposed to mouth wash. For that to prevent infection you'd need contact between the mouthwash and the virus.

So maybe mouth wash helps or maybe it's useless because people are getting infected in their nose or before they use mouthwash. Pretty hard to say but this study doesn't tell you anything actionable.

N=1 but I already stopped a cold that seemed to be developing this past weekend. Fairly harmless to try at the onset of feeling something starting.

Humming can help too https://news.ycombinator.com/item?id=24780570

Unless you're in Australia or New Zealand, how would you even have caught a cold? Even with places partially reopening, it seems more likely it was allergies.

FWIW, a recent clinical trial appeared to show that nitrous oxide is an effective treatment for Covid-19: https://www.businesswire.com/news/home/20210315005197/en/UK-...

Would be pretty cool if we had a pill that was, say, 20% more effective and 300 times more expensive.

The March 23 press release Pfizer Initiates Phase 1 Study of Novel Oral Antiviral Therapeutic Agent Against SARS-CoV-2

https://www.pfizer.com/news/press-release/press-release-deta...

> Pfizer is keeping schtum about the detail of the lab tests

I love journalism because I often learn new words to improve my communication at work. “Keeping schtum” is not an idiom I’ve ever heard before but I will certainly consider using it with my colleagues.

CyberRabbi, you should brush up more on your Yiddish for schmoozing.

As a side note on Germanic loans, I've been getting a lot of mileage out of ersatz at work for my hacks.

Oh wow schtum is German? I just assumed it was English. You learn something new every day. Ersatz is a good one, I gotta use that. Thanks for sharing :)

The German word "stumm" means silent or mute.

Wait I thought it was schtum?

It's Yiddish

Well, if it inhibits, it needs to be renewed at the same rate it is consumed to maintain the inhibition. Thus a saturation dose(freezes ALL that protease inhibition needs to be administered.) The body will degrade/metabolise/excrete this protease = an effective half life. The body's adaptive immune system will also increase to block various aspects of the ways and means the virus uses to reproduce = might block the protease or might stop it being made. In any event this will be a good adjunct to a vaccine to freeze the virus in t's tracks until it can be killed.

This one is also promising: https://www.clinicaltrialsarena.com/news/debiopharm-begins-a... as an aside it is also potent against hepatite C and Myopathies (related to collagen VI)

There is a video Ad popup or something that keeps appearing after I hit close, how do they expect a user will read the article with an annoying and distracting video next to it? Awful UX.

"clean-living adults"

A phrase I was totally unfamiliar with, and not really sure of what it means in context. Non recreational drug users? Non-McDonalds eaters? Only eats nonGMO, organic foods? Bathes regularly?

Maybe something to do with household cleanliness? I know when I go into dirty buildings my allergies mess me up.

Not sure exactly where they got that from, but here's the registry for the US phase 1 trial (https://www.clinicaltrials.gov/ct2/show/study/NCT04756531)

The last condition of the exclusion criteria is "Use of tobacco or nicotine containing products in excess of the equivalents of 5 cigarettes per day or 2 chews of tobacco per day", which seems somewhat related.

I wonder what the metabolic argument is (if any). Maybe it's something else. Really interesting regardless -- anyone know why there's this restriction?

COVID has a serious effect on one's lungs. Smoking does as well. I'm sure they would prefer to see how the medicine works on healthy subjects as a baseline. If it doesn't have the same effect on smokers as the baseline, then you can infer from that. If you just get tainted samples from "diseased" lungs of smokers in the original testing, then that could skew the results. That would be my SWAG.

True, true. Maybe the chewing tobacco is meant to be a proxy for smoking earlier in life.

> "clean-living adults"

This is not an ordinary term-of-art in pharmaceutical research.

Might be reporter's paraphrase of "healthy adults" i.e. not obese, hypertensive, no regular/heavy alcohol or drug use, no chronic conditions, etc.

Why taking a pill when you could just TRASH YOUR TV?

US/CA/UK now have another thing to hoard, nice. RIP the rest of world.

Pfizer is certainly becoming the leader here against COVID it would seem!

> Every detail has been specified in advance. In Phase 3, for example, a high-fat breakfast is defined as: “2 eggs fried in butter, 2 strips of pork bacon, 2 slices of toast with butter, 4 oz. of hash brown potatoes, and 8 oz. of whole milk… eaten in 20 minutes”.

Quite some details! Presumably this part of the testing is to see if large amounts of fat shouldn't be consumed along with the pill.

I cannot imagine consuming that much food that quickly... what is this supposed to represent?

- 2 eggs: 150 cal

- 2 bacon strips: 50 cal

- 2 toast slices: 150 cal

- 4oz hash brown: 370 cal

- 8 oz whole milk: 100 cal

Before butter and oil, that's over 800 calories...

when i was 20, “monday”.

Two minutes to eat an egg or strip of bacon doesn't seem impossible.

I could easily eat one egg or one strip of bacon in 2 minutes. That doesn't mean I could repeat it 8-10 times without discomfort.

8-10 times, what do you mean? There are only two of each in this meal.

I was referring to the total number of items in the meal. I rarely eat buttered toast, and fried hash browns are pretty heavy (though tasty, to be sure!). I also haven't drunk whole milk since I was 2, so all together this would be quite a meal for me. Each of these items is no problem to eat in 2 minutes, but when you stack them all together it ceases to be a joy to eat (at least for me). I could do it once, but if this is supposed to be an every day affair as part of a pill regimen, I wouldn't love it.

That’s not much at all, though I cut the hash browns and up the eggs and bacon.

Just this morning I probably had 8oz of hash browns, three strips of bacon, an egg and half a pancake with butter. Plus a mocha frap.

Granted, I'm medically prescribed a high fat diet. But there are people who eat that way, sometimes because they work hard and are big guys, so 2000 calories a day would be a starvation diet.

Working hard doesn't consume many calories, as far as I know.

There's some extremely cases like training for the Olympics or body building, but overall, peoples energy usage is pretty similar

That contradicts everything I've ever heard. It varies by both activity level and weight of the person in question.

https://www.health.harvard.edu/diet-and-weight-loss/calories...

Yes, and it varies immensely by amount of activity.

I add at least 1500-2000 calories a day when I am lifting in addition to normal training (as in, 1-2 hours of intense exercise every day).

I think it's not so much the total calories, but the sheer amount of fat. That is, if we send the pill down your GI tract with 1/4 of grease, will it still work?

Presumably their "high-fat" condition has to be fattier than any reasonable person would eat on a regular basis, so that it establishes a useful upper bound. If it was just a couple eggs and hash browns, then finding it's still effective wouldn't be useful because some people eat fattier breakfasts than that.

So, I'm getting the feeling that you might not be a regular at Waffle House.

Yes it's a big breakfast but if a normal diet is 2000-2500 calories per day, 820 for 1 meal doesn't seem that weird.

People in home office should probably be on 1600-1800.

"People" come in a lot of shapes, sizes and other activity levels. One-size-fits-all recommendations tend not to fit very many.

How does one's office environment relate to how many calories they consume?

If you lift weights or do other strenuous exercise 3-4k calories a day is needed. The trick with calories is just to not consume more than you are using if you don't want to gain weight.

If you're a 50 year old, 5' tall, 100 lbs lady, then sure.

The basal metabolic rate for a 30 year old male who is 5'10" and 160lbs is 1700 calories. So that's how many calories they burn by merely existing and breathing and being warmblooded. Your argument is that someone working from home only uses a max of an extra 100 calories a day over BMR? Doubtful.

> what is this supposed to represent?

America.

Even ignoring the calories that’s a huge volume of food to eat in 20 minutes. I legitimately couldn’t eat two pieces of toast and drink 8oz of milk that quickly without getting sick.

Since you’re expressing your amazement at this, let me just point things out from the other side: being unable to eat two slices of toast and a glass of milk in 20min without a tummy ache sounds very weenie to me. There are people of all shapes in the world with all sorts of fortitude. That breakfast wouldn’t even test mine. Except maybe when coming out.

Or maybe they are spending too much time on a device scrolling through a feed instead of actually eating?

I find that extremely difficult to believe.

Difficult to believe? That not everyone has a massive, bottomless pit for a stomach? I don’t know why that’s extremely difficult to believe since everyone is different and I’m hardly unique.

But you’re certainly not the first. I’ve had plenty of waiters who are convinced I hated my perfectly delicious meal simply because the serving size is way too big for me. I’ve had colleagues make “jokes” about my “girlish figure” when I fail to clear my plate at a business lunch. And someone on the internet even called me “a weenie” while telling me that people come in all shapes! (I mean, honestly?)

For some reason people seem to have a hard time comprehending that everyone isn’t exactly like them. It is what it is. But what it’s not is my problem.

What's hard to believe is that only people with massive bottomless pits for stomachs can handle eating two pieces of toast.

That's about a third of the daily calorie allowance for the average adult. Doesn't sound all that extreme.

Farm and weekend breakfasts are like this, and standard to get at breakfast places in the US. I've had similar at a hotel in Amsterdam, honestly (though it was a buffet). It isn't really that much food or calories as long as you are hungry when it is served.

This looks like a small snack. Swap the milk out for almond milk tho.

That is a totally normal amount of food and drink for an active adult male to consume in a 20 minute meal. That said I do wonder if they should adjust the prescribed diet for people with different calorie requirements.

Bacon more than 50 cal.

That's breakfast of champions right there, what we all wold like to think we could get away with eating ...

If eating a massive breakfast with it helps the pill work, then it's finally England's time to shine.

UK gave the world its traditional breakfast, USA gave the world the all-day breakfast

America: You’re welcome, world :)

But baked beans and black pudding aren't listed in the protocol :(

Can't be an English breakfast, there were no beans nor tomatoes

I expect the medium term survival of the participants to this particular trial to be zero.

Sign me up!

Huh, that’s nothing compared to an average keto diet.

Yes. Fat is generally non-polar molecules so has a different solubility profile. This in turn may significantly change absorption, and the location of absorption (stomach v small intensive v large intestine etc).

Or because they think the pill will cause stomach issues. I had one medicine that caused gastro side effects: Taking the pill on a full stomach or while eating a full meal was really important, especially at first. This breakfast would have done well.

blows my mind to see nearly every single comment here being overtly positive—bordering on unconditional reverence—with regards to this massive pharmaceutical corporation. apparently we just trust everything they say these days? skepticism is just off-limits for these guys? when did this happen?

Hacker News is a misnomer. No one here understands what actual hacker values are/were.

Apparently Sorrento Therapeutics already has a cure that’s bogged down by testing. I guess they don’t have the connections to fast track it.

This is an oddly pessimistic view - what are you implying?

What are you on about? They're actively testing Sorrento's treatment, yes (it's not 'a cure'; it -is- a treatment for those in the ICU. It's an infusion). This pill is also 'bogged down by testing'; if testing is successful it will be available later this year. Sorrento's treatment is going into phase 2; this pill is just entering phase 1.

Sorrento also got $34 million from DARPA for their treatment, I might add. Is this just a general "Rargh, drugs shouldn't take so much testing!" complaint, or are you asserting that Pfizer, Moderna, and J&J are getting preferential treatment that Sorrento isn't?

From what I have been reading, it’s saved the lives of everybody who it’s been given to so far but I haven’t seen much coverage of it outside of the stock reports.

Just struck me as odd that it’s bogged down in more testing when it seems to have a near perfect record. Blows my mind that India and Brazil aren’t begging for it considering the scope of their current situations.

After following it for the last year, suddenly seeing the Pfizer option out of nowhere just struck me as odd.

You better have an actual citation for this miracle drug.

Because this sounds a bit like remdesivir, one of the earlier candidates for a savior drug that, once we had more statistical power, didn’t really pan out.

https://www.nejm.org/doi/full/10.1056/nejmoa2007764

Also, if it’s an IV infusion, in a poorer country with a massively strained health care system…well, good luck actually deploying it.

A little of both really. While no one it's been administered to has died, it's not been administered to many people, and it has been administered without control. Which isn't shocking; that's the first phase of human testing, just see if it seems to actually help, and not create issues itself. They're setting up for tests with a control group next.

https://investors.sorrentotherapeutics.com/news-releases/new...

It could indeed fizzle like Remdesivir. Just, yeah, the data, while promising, is so small it tells us nothing. Hence why the clinical trial process.

Thank you for linking to the actual drug, versus the inscrutable parent comment.

And from that link…

“All nine patients…”

…and from the parent…

“it’s saved the lives of everybody who it’s been given to so far”

Well, when N=9, whoop-dee-doo.

Also, while that sure could be promising, color me quite surprised if they can up human-derived stem cells to treat a surge like they are seeing in India.

Define "cure?" Also, if they had something solid larger companies would be salivating to jump on it (and Sorrento would reap royalties for a solid chunk of this).

Care to clarify which one? They’ve got a lot in the pipeline.

https://sorrentotherapeutics.com/research/covid-19/

Plot twist: The pill is called hydroxycholroquine.

Is Pfizer taking advantage the emergency declaration to fast-track this pill? If yes, we need to be wary.

Remember, there's no value to Pfizer to cure things like the common cold.

Ever have one of those experiences in life where you write people off as "conspiracy nuts" until you have to deal with the issue yourself so in desperation you try their crazy?

Well there's no way to convince the disbelievers but Ivermectin is already a cure for covid, weak and imperfect but it definitely does something. I know and believe only because it personally saved me from death's door.

Don't try mentioning this on twitter or facebook though, you'll get your account blocked/banned.

Funding for a more targeted and powerful cure definitely should happen but there is something really really weird in life when you see something being buried that you know is different than the official stroy.

Doesn't help that every quack is coming out of the woodwork to try to cash in on it somehow, not by profit from the drug itself but their only 15 minutes of "fame". But there has to be someway to fix that signal-to-noise ratio when it comes to saving people's lives.

So you took it when you had Covid and you didn’t die so you conclude it works? You realize that the most likely thing to happen for anyone at almost any stage of Covid is to actually get better right? You took a powerful anti parasitic drug and decided the default course of action was the result of this drug?

This is like saying you broke your arm and prayed to god and you’re alive so god saved you.

look I'm not going to sit here and argue with some random person on the internet (and fwiw I'm atheist) I was literally in your disbelieving shoes and I still don't know how to convince people or if I even want to waste the effort trying

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261036/figure/...

just sit back for a moment and consider the possibility you are being lied to not by consipiracy but rather much easier apathy and ivermectin actually has proven antiviral properties that actually do something, just not specifically targeted to covid19 so it's not a "miracle" by any means

I was not just sick with covid, I was at death's door. Steroids were not doing anything/enough and pneumonia/clots were destroying my lungs. This was very early on in the pandemic and there were no treatments available.

Again, I've got nothing to prove, I don't expect people are going to listen, I'm just putting this on the record. Something's up with this being not just dismissed but buried.

Okay not everyone’s going to blatantly disregard any reasonable hypothesis. Now that you have linked to articles it is at the least, reasonable. I went through the review and it’s clear no one has actually tested it systematically in vivo. A lot of drugs have antiviral activity in vitro, I know because I used to do those assays. Let’s just say that it’s worth testing this drug in Covid patients at the least.

I used to believe IVIG will also work on Covid patients, but given the small number of studies that have been done and the fact that no one noticed any effects accidentally suggests that there’s probably not much of a fire under that smoke. Two of the most important qualities one needs as a scientist is to embrace crazy but reasonable hypotheses and drop them the moment it becomes clear they are not full true.

Please also note that The fundamental issue with Covid is that it’s actually mostly mild. The majority of people don’t get serious from it. By the moment you do get serious from it, no drugs work anymore. That’s why dexa is the best medicine till now and no ones bothering with the antibody cocktails even after it’s proven to be worthwhile. By the time people are seriously sick I doubt even ivermectin would work that well.

Anyways glad it worked for you and hope someone does test this drug systematically so we will know for sure and sooner rather than later.

Could you be more specific about your experience with Ivermectin? Its side-effects can be pretty serious, right?

It's virtually impossible overdose or have bad effects from ivermectin, it's not that HCQ nonsense. Ivermectin is even given to people to self-dose in countries for it's original anti-parasitic purpose without fear of them using too much.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261036/figure/...

The way to convince the disbelievers is with large randomized controlled trials.

And it's not like Ivermectin wasn't studied. In randomized control trials and was found to be probably ineffective. Still being studied by various people. But also likely that even if it were effective the doses required would be too toxic for humans. So not a wise thing to spread around as "health advice" and presumably why Facebook etc have clamped down on this.

See https://en.wikipedia.org/wiki/COVID-19_drug_repurposing_rese...

Also if it worked, I'm pretty sure Merck (the creator of Ivermectin) would be all over selling it for that purpose.

it's off patent for decades now, it's less than 10 cents a pill in the third world and less than a dollar a pill in usa, there's no money to be made off it, which might be the problem, I don't know

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261036/figure/...

also see ivmmeta for studies, endless studies

I'm not going to sit here with tinfoil hat, I don't really care anymore because we have the vax now, but something was up with the way this is being buried, not just dismissed but literally buried, it's weird.

I don't see it as buried at all. Multiple studies done. All out in the open.

It's so easy to bypass the "but it's off-patent and therefore not profitable"

A) homochiral enantiomers

B) analogues

C) cocktails

"Our formulation of Norivermectin plus Foobarmanolib is 10% more effective and has 3.5% fewer incidence of side effects. The small increase in effectiveness is projected to decrease hospital stays by 4.5 h, leading to 2 million lives potentially saved."

Boom, profitable, patentable COVID cure. Doctors could still prescribe plain ivermectin off-label but would be incentivized by pharma reps to sell name brand.

Norivermectin and Foobarmanolib are hypothetical, of course. But the trick is real, see escitalopram, armodafinil, aripiprazole + antidepressants, etc.

ivmmeta probably has all the data you want

it turns out hcq is actually quite effective, shame it got culture-war'd: https://c19hcq.com/

Is the culture war the thing where over 120 studies found it had no value over placebo? Weird name for it, but yeah. Hydroxy chloroquine was found to be totally ineffective in 95% of studies. That's exactly as you'd expect with a p < 0.05 publication threshold.

perhaps you should take a look at the link; there is even a nice meta analysis https://hcqmeta.com/

As a layman, my main observation with the link is they seem to be computing a statistical measures over the studies to get a meta-result. But that isn't necessarily a statistically valid methodology, for the following reason: it is like if someone gave you a bunch of grapes and and apple, and asked you to estimate the average size of apples. If you simply averaged all of the fruit given, you might end up claiming they are about the size of a quarter. But if you look closer, some of those samples might have larger significance and be more useful than the others.

That doesn't necessarily mean the site is invalid or its conclusions, and I don't personally care much which "side" is right. But does that analogy help explain why this can be a tricky problem, and why many here, including myself, defer to "experts" like the NIH (who ran one of the largest studies of hcq)?

A few of the more highly touted studies I read even showed that early use of hcq by mildly sick individuals at home had better outcomes when compared against already hospitalized people who were already very ill sick with covid, regardless of their later treatment. But when larger studies were done that actually tried to compare apples-to-apples, they didn't show much effect. I agree, that is an odd thing to call a "culture war", unless he meant science against wishful thinking? And hcq perhaps may even have some effect, but just not one worth the cost of the drug and the risk from missing out on better treatments that are available.

I wonder why OP wants to believe in hcq, if they'd like to respond?

Worse than innefective; some studies have found that the HCQ arm fared worse than placebo.

Not to mention the more fantastical misuses out there, such as nebulizing it straight into the lungs.

Simplest argument against HCQ. With trump promoting it so much, so many people used it as to define a large sample of people. It didn't stop the second surge, and there were post surges in trump supporting areas, so you are pretty simply proven wrong...

And in that vein, Trump was at one point taking hydroxychloroquine, which sure did not prevent him from ending up in the hospital on oxygen.

Reply on news.ycombinator.com