"Once someone is infected with SARS-CoV-2, the immune system is mobilized. As the virus replicates, cell and viral debris or virions may interact with the nAChRs blocking the action of the cholinergic anti-inflammatory pathway. If the initial immune response is not enough to combat the viral invasion at an early stage, the extensive and prolonged replication of the virus will eventually disrupt the cholinergic anti-inflammatory pathway seriously compromising its ability to control and regulate the immune response. The uncontrolled action of pro-inflammatory cytokines will result in the development of cytokine storm, with acute lung injury leading to ARDS, coagulation disturbances and multiorgan failure. Based on this hypothesis, COVID-19 appears to eventually become a disease of the nicotinic cholinergic system."

"Nicotine could maintain or restore the function of the cholinergic anti-inflammatory system and thus control the release and activity of pro-inflammatory cytokines. This could prevent or suppress the cytokine storm. This hypothesis needs to be examined in the laboratory and the clinical setting."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192087/#!po=22...

This article is actually spot on, and is a pretty good cheat sheet.

I have a very rare immune mediated neurological disease affecting nicotinic receptors in my peripheral nervous system called autoimmune autonomic gangliopathy.

I am ganglionic nicotinic acetylcholine receptor antibody (nAChR, α3 subunit) positive, at high and abnormal levels, which means this antibody blocks signals at the ion channel level, in my neurons of my autonomic ganglia, which is supposed to control bodily functions—but it malfunctions in my body. Some people with the disease I have, (supposedly ~22% according to this PMC article on PUBMED: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536520/) have alpha7 subunit nicotinic acetylcholine receptor antibodies (α7 nAChR antibodies), which effectively block signals in general, affecting transmission of signals via the ion channels of neurons in the central nervous system. This type of central nervous system blockade of the autonomic nervous system causes inflammation.

The article that the above poster linked is an ominous warning for people like me, who have the same very rare disease I have, even if one is just alpha3 nAChR antibody positive only—and is not also alpha7 nAChR antibody positive. I am glad I have been taking extreme steps to protect myself.

Also, some people that never recovered from COVID-19 have sympathetic nervous activity have similarities to the condition I have.

Researchers may want to search for autoimmune autonomic ganglionopathy on PUBMED: https://pubmed.ncbi.nlm.nih.gov/?term=Autoimmune+autonomic+g...

You also may want to search for autoimmune autonomic ganglionopathy and the alpha7 nAChR on PUBMED: https://pubmed.ncbi.nlm.nih.gov/?term=Autoimmune+autonomic+g...

Or α7 nAChR antibodies, which in theory would have a similar but different effect as the stuff that the poster above me linked: https://pubmed.ncbi.nlm.nih.gov/?term=%CE%B17+NAChR+antibodi...

As for the people who have a post COVID-19 inflammatory syndrome affecting their sympathetic (as in autonomic nervous system) nervous system, as in sympathetic over activity, they very likely have a form of dysautonomia:

Researchers may want to look into these antibodies/tests, in which there are several peer reviewed articles available to read. However, several of these tests are not commercially available in the US, but can be mailed/performed in Germany. See: https://www.celltrend.de/en/pots-cfs-me-crps.html

There is an immune mediated dysautonomia panel available at the Mayo Clinic (which I was found to have one of the antibodies), but one is far less likely to test positive for something in these screens. See this panel: https://www.mayocliniclabs.com/test-catalog/Overview/92121

A lot of this immune mediated autonomic nervous system stuff is just starting to emerge and come to fruition.

I remember seeing similar articles. While I don't understand the science behind these findings, my understanding is that smokers are less likely to catch COVID, but if they do, then their symptoms are significantly more severe than those of nonsmokers.

incorrect; smokers are shown to be substantially less susceptible to both catching covid and developing severe symptoms, a finding that has been demonstrated independently in (at least) france, china, and the USA:

> Conclusions and relevance: Our cross sectional study in both COVID-19 out- and inpatients strongly suggests that daily smokers have a very much lower probability of developing symptomatic or severe SARS-CoV-2 infection as compared to the general population.

> Very recently, the US Center of Disease Control reported an analysis of current smoker rate among US COVID-19 patients which was found to be 1.3% for the whole population of COVID-19 patients, 1% for outpatients, 2% for patients, not hospitalized in an ICU, and 1% in intensive care unit (ICU)-admitted patients

https://www.qeios.com/read/WPP19W.3

in all of the mentioned countries, only about 1% of ICU cases are smokers. this has (perhaps unsurprisingly) not been widely reported.

Both SARS-Cov-2 and nicotine bind to the ACE2 receptor. One hypothesis is that because SARS-Cov-2 has to compete with nicotine for the receptor it ends up being less effective. Another hypothesis is that smokers tend to do better because of nicotine's effect of reducing inflammation.

Seems more likely to me they're just lying about being smokers- 60% admit to being former smokers. Inpatient hospitalizations also almost all suffer from serious comorbid conditions like hypertension or diabetes, which probably causes many to smoke less. Less so with the outpatients (<20%) but I would not be surprised if it was because unhealthy people getting sick, and those unhealthy people don't smoke because it would be bad for them.

> Seems more likely to me they're just lying about being smokers

Being a smoker has been a standard part of your medical history for a long time now for obvious reasons. There's no reason to think there is a coordinated strategy for lying about smoking in the context of a pandemic (much less revising patient medical histories, which would be the medical service industry lying).

50%+ lying about smoking in the face of potential (or actual) respiratory failure is laughable.

The study isn't talking about history, it's talking about current smokers and many of the comments on the paper bring up concerns with how specific that is, and how many could have quit days before going to the hospital.

I don't know where you got 50%+. The outpatient group was 5.3% current smokers vs expected (adjusted for age and sex) 26.9%. For inpatient it was 4.4% vs expected 17.9%. The fact that both groups had the same reported rate of current smokers (within experimental error) but very different expected rates says to me that you're only getting the people who are honest or simply incapable of quitting even while sick.

Also, see this concern brought up:

> Finally, and I believe this to be the most significant piece of data supporting the null hypothesis, the prevalence of never-smokers in the general population is approximately 0.75, if one subtracts the smoking incidence rate from 100. In your patient groups, non-smokers are strongly under-represented by about a factor of 2 relative to the general population, with 31% of outpatient and 32% of inpatient being labeled as never-smokers. This suggests to me that any amount of smoking actually puts one at risk for contracting COVID-19 as defined by this paper.

I'm not sure I understand the quoted concern? The study they referenced[1] showed that France was ~37% never smokers average over all ages (nowhere near 75%), and their in- and out-patients were about the same fraction (Table 2) for male, a little lower for female. The big discrepancy is under-representation of current smokers, and over-representation of former smokers. But their patients are old, and I'd expect older people to have more former smokers, since they've had more time to start and stop and since the general trend in smoking is down. I don't see that broken down by age in the paper they linked though. Maybe we'd have to dig in to the raw data, or maybe it's just not available?

In any case, many other studies of COVID-19 have found similar results, and studies of different respiratory diseases have not. I'd initially just thought people were lying too, but at some point the evidence becomes overwhelming--if the protective behavior were anything but smoking, then people would have accepted it long ago.

Of course smoking is far deadlier on average than the coronavirus, per my calculation elsewhere in this thread. No one should start smoking because of this, but I do see enough evidence e.g. that a nursing home patient (who's at very high risk of death from coronavirus, and likely to die of something else before smoking-related diseases could develop) shouldn't quit. Vaping probably gets any benefit with almost none of the health risk, though that's speculative.

1. http://beh.santepubliquefrance.fr/beh/2019/15/pdf/2019_15_1....

Maybe they're lying on the paper work because they're afraid their insurance rates will go up.

The studies are not being conducted in the US alone.

As said by the Dr Gregory House on 'House MD' series, 'everybody lies'

Maybe they just drop dead immediately in their homes? /s

Seriously though, it's baffling because smoking causes so many underlying health problems that don't go well with COVID. Also, smokers have a depressed immune system compared to nonsmokers, so it would seem to suggest they'd be less likely to fight off an infection like this.

In a lot of cases, COVID-19 symptoms involve an immunesystem overreaction, which causes massive inflammation and organ damage all over, so having a depressed immunesystem might help there.

That is contradicted by the studies in the linked article

>smokers with a positive Covid-19 test were more than twice as likely as non-smokers with coronavirus to be hospitalised.

> This aligns with research from the US which found hospitalised smokers with coronavirus were 1.8 times more likely to die.

i don't think it is a contradiction; "a very small fraction of smokers contract covid or end up in the hospital due to it; those that do are more likely to die"

This sentence: "smokers are shown to be substantially less susceptible to both catching covid and developing severe symptoms"

is contradicted by the study showing that smokers with covid are more likely to have severe symptoms than non-smokers with covid.

Also in countries like India and Pakistan with very high percentage of smokers, we are seeing very low COVID19 cases.

While a lot of people are skeptical of the official numbers from these countries, I think they have free media and if cases were high, we would have known.

I haven't read this article in-depth, but at a glance I did not see this discussed there: can't this simply be explained by smokers generally having a lower life expectancy than non-smokers?

If most people that have severe COVID complications and end up on the ICU are aged 80+, and generally smokers die before that age from smoking-related complications, doesn't it naturally follow that most people on the ICU will be non-smokers? Smoking will have killed the smokers before they become part of the high-risk group, after all.

Weird sentiment to think the researchers wouldn't identify and correct for such an obvious factor.

Correcting for something is much easier said than done, and it is very often done incorrectly. Blindly trusting researchers to do so is a mistake.

Here is a quote from the abstract of the paper linked above:

> Results: The inpatient group was composed of 343 patients, median age 65 yr: 206 men (601%, median age 66 years) and 137 women (39.9%, median age 65 years) with a rate of daily smokers of 4.4% (5.4% of men and 2.9% of women).The outpatient group was composed of 139 patients, median age 44 years: 62 men (44.6 %, median age 43 years, and 77 women (55.4 %, median age 44 years). The daily smokers rate was 5.3% (5.1% of men and 5.5 % of women). In the French population, the daily smokers rate was 25.4% (28.2% of men and 22.9% of women).

The average daily smoker rate is taken as-is over the whole population, and compared to the smoking rate of people of age around ~66 years, despite the article itself stating that the percentage of daily smokers is lower for old people and higher for young people.

So already in the abstract they have made a mistake and forgot to correct for age. I have not read the rest of the article in enough depth to judge fully, but I would absolutely not blindly trust researchers to always do this correction in an appropriate way.

Most of these studies correct for age because of that.

I saw an analysis from a epidemiologist who said the result is due to naive over adjustment for confounding variables. Specifically if you treat related confounding variables as if they are independent you end up with garbage.

They also said elsewhere that a lot of researchers from outside epidemiology are running really bad studies and publishing papers.

He's almost certainly wrong, the effect size on this one is astounding. See for example this: https://www.qeios.com/read/WPP19W.3

Even with conservative assumptions, smokers in this French study were 4 to 5 times less likely to be infected.

Keep in mind that drugs being tested are considered good when they reduce mortality by 10%. We're talking 75% reduction in infection rate here, and no increased mortality in those who are infected. It's really really hard to imagine what sort of confounding factor that could be at play here that would make the effect insignificant.

If the facts speak against what an epidemiologist says, then perhaps we should also use critical thinking there.

Makes me wonder if tobacco in eras of tuberculosis improved chances of individual survival...

Almost certainly not. Nicotine is known to downregulate the recptor that SARS-CoV-2 uses for entry.

They are just as likely to catch it, but the symtoms are less severe in more cases than non-smoker.

They give nicotine patches to nurses in pilot studies, how ironical :D

Do you have source?

Smoking decreases the amount of certain enzymes that COVID binds to in order to infect the lungs. Less enzymes means a lesser chance of catching the virus, but if caught, the person will likely have a more severe case due to the decreased lung capability.[0][1] The figures that I have seen previously did show a very significantly decreased risk of catching COVID, and I'm surprised it hasn't been investigated far more.

Edit: I had that wrong, it seems nicotine increases ACE2, but also binds with ACE2 decreasing the amount of available enzymes overall that COVID could bind to.[2]

[0]https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_... [1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191112/ [2]https://arxiv.org/abs/2004.14943

I quit vaping back in mid-Feb when it was obvious things were going down. But then I took it back up in May because the studies with very large N (ie, millions) had started coming out of the UK showing even literal smoking did not increase your covid-19 risk after infection. And you can bet if it did, at all, there'd be big news about it. But instead study after study shows nothing of significance either way.

Not to imply you suggested otherwise, but smoking costs far more life years than the coronavirus. Anyone quitting is doing a good thing for the wrong reason.

Vaping is less clear--I do think there's some non-negligible chance that for the next couple years, it will be a net benefit to public health. That would be funny, considering how hard the public health authorities worked to smear nicotine vaping with the deaths from adulterated (vitamin E acetate) marijuana cartridges last summer.

I think it's too early to absolutely determine the life expectancy cost of a covid infection. The pathology is so diverse with this virus it would take a very complex calculation and obviously years of observation to make your claim.

https://www.nature.com/articles/s41591-020-0968-3

To quote this paper's author: "This virus is unusual and it's hard not to take a step back and not be impressed by how many manifestations it has on the human body"

and to quote the paper itself: "In a study of nearly 5,500 patients admitted with COVID-19 in a New York City hospital system, (acute kidney injury) occurred in 37%, with 14% of the patients requiring dialysis. "

and that is only one of dozens of conditions in their findings.

Patients who die of coronavirus have median age of 78[1], and thus life expectancy around ten years. Younger decedents will have a disproportionate effect on average life years lost, so using the median life expectancy does tend to underestimate that. On the other hand, the patients who die were probably less healthy than the average for their age before they got infected (e.g., the huge mortality in nursing homes; nursing home patients already had an average life expectancy around a year[3]), which would make us overestimate. Somewhat arbitrarily, let's say those cancel, so a coronavirus death costs ten years of life.

The average IFR over all ages is 0.7%[4] from a recent meta-analysis. If we're considering prospective smokers, then I guess we should exclude young children, so let's (again, somewhat arbitrarily) bump that up to 1%. That would mean a coronavirus infection in a random individual (age weighted according to population of prospective smokers) costs 0.1 years of life expectancy.

But smokers have life expectancy about ten years[5] shorter than non-smokers! So there's lots you could find to argue about in my rough calculation above, and I agree that patients who don't die immediately still lose some yet-unknown number of quality-adjusted years of life; but unless you think you can find two orders of magnitude, smoking is unquestionably more dangerous. That doesn't mean the coronavirus is harmless, just that smoking is really bad.

1. https://www.cdc.gov/mmwr/volumes/69/wr/mm6928e1.htm

2. https://www.ssa.gov/oact/STATS/table4c6.html

3. https://www.ucsf.edu/news/2010/08/98172/social-support-key-n...

4. https://www.medrxiv.org/content/10.1101/2020.05.03.20089854v...

5. https://www.cdc.gov/tobacco/data_statistics/fact_sheets/heal...

You may not know and it may be very hard to determine the ultimate loss of life expectancy in younger people. I read somewhere that people that survived a bad bout of polio often suffered poor health later in life. Long term kidney damage could easily be something a person could live with for decades before it came back to bite them.

Using the adulterated marijuana cartridges as a way to push anti-vaping campaigns was the same sort of disingenuous technique use to get people to not wear masks to save them for health care professionals at the beginning of the COVID epidemic. The authorities think the public are too stupid to understand or react to facts, so they lie to them and it ends up backfiring.

Uhm. It ended up backfiring in the US. Here in the Netherlands they said the same thing about masks (and made it pretty clear why this was said) and it ended up being just fine. It seems abundantly clear that your authorities simply had no such plan in mind.

Dr. Fauci admitted directly in an interview that they had exactly such a plan in mind.

> Vaping is less clear--I do think there's some non-negligible chance that for the next couple years, it will be a net benefit to public health.

By "net benefit", you mean because it can help people quit actual smoking, right?

I mean because nicotine might be protective against the coronavirus, and that protective effect might outweigh the harm of vaping. Certainly not proven (and please nobody start vaping because of that), but there's some weak evidence and it's funny.

Of course vaping's real benefit to public health comes from smoking cessation as you say, since smoking is (per my comment above) really deadly. I was disturbed to see the public health authorities blaming nicotine vaping for the lung injuries last summer, given (a) the ample evidence for vitamin E acetate as the cause; and (b) the cost in mortality from smokers who got scared by their misleading warnings and either didn't switch to vaping or switched back to cigarettes.

> you can bet if it did, at all, there'd be big news about it.

Mildly OT, but, don't depend on popular news to get you the important info of the world.

I started out this discussion by talking about the primary scientific journal sources I'd read, and in particular the one from the UK national health system. Unless I start doing the research myself it's hard to depend less on popular news. But that doesn't mean it isn't a useful indicator.

> “At the time of this review, the available evidence suggests that smoking is associated with increased severity of disease and death in hospitalized COVID-19 patients. Although likely related to severity, there is no evidence to quantify the risk to smokers of hospitalization with COVID-19 or of infection by SARS-CoV-2 was found in the peer-reviewed literature. Population-based studies are needed to address these questions.“

https://www.who.int/news-room/commentaries/detail/smoking-an...

Gwern's page on positive/negative effects of nicotine considered independently of smoking:

https://www.gwern.net/Nicotine

One of the causes of the second wave in Victoria was apparently staff at a quarantine facility sharing a lighter, alongside a security guard having sex with quarantined arrivals.

You can just say idiocy :D

There is also this study which says smoking in young adult increases the risk of Covid progression - https://www.ucsf.edu/news/2020/07/418081/1-3-young-adults-ma...

Have you actually read the article? The study's methodology is super confusing and just plain doesn't make sense. From what I can decipher, they conflated obesity, diabetes, smoking, immune disorders, and several other factors all together into a single variable ("vulnerability") and made no attempt to look at the contribution of smoking alone. They also lumped e-cigarettes together with tobacco and cigar smoking.

Well I do remember seeing that in the news cycle earlier in the year and I think it was a loose correlation of interest during the early days of the spread - that smokers seemed to either be catching it in lower numbers or that smokers were seeing fewer symptoms. Of course correlation != causation, and many odd rumors from March have since been debunked.

Perhaps the article has been updated since you read it. It now includes this (with a link to the studies)

> smokers with a positive Covid-19 test were more than twice as likely as non-smokers with coronavirus to be hospitalised.

>This aligns with research from the US which found hospitalised smokers with coronavirus were 1.8 times more likely to die.

I was perplexed by this study as well and in a dilemma. I had to choose between a couple of new studies showing smoking might reduce my risk of Covid vs decades of studies showing smoking causes cancer. So I aimed to quit smoking and get healthy to reduce my risk of cancer and Covid.

...there are downvotes in HN!?

There are tons of hidden HN features unlocked at different thresholds. https://github.com/minimaxir/hacker-news-undocumented

501 karma for downvoting

Oh wow. I lurk 99% of the time, so I doubt I'll ever reach those heady heights. Thanks for the link, though!

Yeah. Once you’re above a certain level of karma points you can downvote.

I can downvote but rarely do it. Also a comment can only be downvoted 4 times. After that downvotes are not counted anymore if I remember correctly.

I've had comments voted lower than -3 (you start at 1) plenty of times. My favorite one is one comment criticizing Microsoft that oscillated from 25 to -10 a few years back (yeah, I refreshed this one quite a lot to see how it changed, that was fun).

But I don't remember anything lower than that recently, so it can be a new change.

5 times, the lowest you can go is -4.

You’ll get the ability to downvote when you reach about 500 karma.

Only for the 1%

It makes sense and something that goes against another agenda so something that couldn't be spread by mainstream news widely.

Hospitalization is one of the good outcomes.

The people dropping dead in the streets, like we saw so much of in Wuhan (smoking population ~50%)-- those are the smokers. Smoking opens up more ACE2 receptors which is like opening more lanes for COVID traffic.

opposite (seriously). it clogs them, causing you to produce more, complex adaptive cycle.

I'm reluctant to recommend quitting

To the virus, the ACE2 sites are just a recognizable external feature to latch onto. The clogged sites might be less of a liability than the unclogged sites, but having more overall makes your cells way more virus-friendly.

Quit now!